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BÀI TẬP CƠ CHẾ PHẢN ỨNG HÓA HỌC HỮU CƠ NÂNG CAO CÓ ĐÁP ÁN

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ẠY M

KÈ Y

Q H

N Ơ N

IC IA L

ẠY M

KÈ Y

Q H

N Ơ N

IC IA L

ẠY M

KÈ Y

Q H

N Ơ N

IC IA L

ẠY M

KÈ Y

Q H

N Ơ N

IC IA L

ẠY M

KÈ Y

Q H

N Ơ N

IC IA L

ẠY M

KÈ Y

Q H

N Ơ N

IC IA L

benzyloxycarbonyl 10-camphorsulfonic acid chlorosulfonyl isocyanate cyclohexyl 1,4-diazabicyclo[2.2.2]octane

methoxymethyl methanesulfonyl

MS n NBS

molecular sieves normal N-bromosuccinimide

NCS NMM

N-chlorosuccinimide N-methylmorphuline

IC IA L

Cbz CSA CSI Cy DABCO

MOM Ms

aryl benzyl t-butoxycarbonyl butyl catalytic amount

m-chloroperbenzoic acid methyl (2-methoxyethoxy)methyl

Ar Bn Boc Bu cat

mCPBA Me MEM

NMO Ns o

N-methylmorpholine-N-oxide o-nitrobenzenesulfonyl, nosyl ortho

acelyl acetylacetonate 2,2"-azobisisobutyronitrile aqueous

liquid meta

Ac acac AIBN aq

liq m

heat

dibenzylidenacetone 1,8-diazabicyclo[5.4.0]undec-7-ene N.N'-dicyclohexylcarbodiimide 2,3-dichloro-5.6-dicyano-1,4benzo-quinone

p Ph

para phenyl

Pr rt s

propyl room temperature secondary

DEAD DMAP DME DMF DMSO

diethyl azodicarboxylate 4-(dimethylamino)pyridine 1,2-dimethoxyethane N, N-dimethylformamide dimethyl sulfoxide

SET t

single electron transfer tertiary

TBAF TBS Tf

tetra-n-butylammonium fluoride t-butyldimethylsilyl trifluoromethanesulfonyl

dppb DPPE EDCI

1,4-bis(diphenylphosphino)butane 1,2-bis(diphenylphosphino)ethane 1-ethyl-3-(3-dimethylaminopropyl carbodiimide equivalent

TFA TFAA TfOH THF

trifluoroacetic acid trifluoroacetic anhydride trifluoromethanesullonic acid tetrahydrofuran

ẠY

KÈ

dba DBU ICC DDQ

Et HMPA hv i KHMDS

ethyl hexamethylphosphoramide photoirradiation iso potassium hexamethyldisilazide

LDA

lithium diisopropylamide

TIPS TMS

triisopropylsilyl triraethylsilyl

tol tolyl TosMIC p-toluenesulfonylmethyl isocyanide Tr triphenylmethyl, trityl Ts TsOH

p-toluenesulfonyl, tosyl p-toluenestdfonic acid

ẠY M

KÈ Y

Q H

N Ơ N

IC IA L

Provide reasonable arrow-push mechanisms for following recations

NaCN (cat) H

EtOH-H2O reflux

IC IA L

benzoin condensation

H O

H CN

ẠY

KÈ

H O

Adams, R; Marvel, C. S. Org. Synth., Coll. Vol.

1941, 94

Provide reasonable arrow-push mechanisms for following recations

A001 O2N

OMe

NaOH H2O, reflux

O O2N

aq HCl

A002 O

H2SO4(cat) OH

OEt

EtOH reflux

SOCl2

A003 O

A004

Y aq NH4Cl

PhMgBr Et2O o 0 C to rt

KÈ

A005

OEt

PhMgBr (2 eq) Et2O o 0 C to rt

Ph Ph Me

O MeO

aq H2SO4

ẠY

MeO

A006

O H MgBr

Me N Me (DMF)

Et2O o 0 C to rt aq HCl

O H

IC IA L

A007 N C N (DCC) O OH EtO

EtO

Me Me OH Me CH2Cl2, rt

Me Me Me O

IC IA L

Me N N Me (DMAP)

(TsOH, cat) benzene reflux

A008

A009

OMe

BnO

OMe

HC(OMe)3 MeOH reflux

BnO

Br2 HBr, (cat)

0 C

ẠY

KÈ

A010

(TsOH, cat)

A011

NaCN, NH4Cl Et2O-H2O 0oC to rt

O Me

aq HCl reflux

H3N CO2H Me

A012 O

DMF, POCl3 0oC then

H2O

Me2N

A013 (HCHO)n Me2NH, HCl

O Me

O NMe2

EtOH reflux

2) Ac2O, reflux

MeO

1) NH2OH-HCl NaOH Et2O-H2O, rt

A014

MeO

IC IA L

Me2N

A015

KÈ

A016

OMe

H2O

MeMgBr Et2O, -40oC

aq H2SO4

ẠY

EtO

Et2O, 5oC

N OH

PCl5

A017

H2NNH2 O Me

K2CO3 triethlene glycol reflux

Me Me

A018

N H

CO2Et

H +

CO2Et

benzene reflux

CO2Et

IC IA L

CO2Et

2) H2O, acetone reflux

N H

1) NaOAc Ac2O, reflux

A019

O +

NaOH

EtOH-H2O rt

NaH DMSO, rt

A021

A020

CO2Et CO2Et

KÈ ẠY

H3O+

CO2Et

A022

1) O

N H benzene reflux

O Me

2) Ac2O dioxane, rt; H2O, reflux

A023

CO2Et EtO2C

IC IA L

1) Br (1.02 eq) n-BuONa (1.0 eq) n-BuOH, reflux

HO2C

aq KOH, reflux; aq HCl 2) heat, 180oC

A024 O

Br2

AcOH 20oC

A025 Br2, PCl3 70 oC

OH O

O Br

H2O

A026 O Me

KÈ

NaOH EtOH-H2O H3O+

Me H HO

ẠY

O Me

I2 (3eq) pyridine, ;

A027

Br2

O O

EtOH 10oC

OEt Br

OEt

H H

A028 1) BH3-THF (0.33 eq) THF, rt Me 2) NaOH aq H2O2, rt

A029 O3, CH2Cl2 -78 oC;

OAc C10H21

OAc

C10H21

OHC

Me2S, rt

OBn

A030

Me Me O

A031

Hg(OAc)2 Et2O-H2O, rt;

OH Me

Hg(OTf )2 (1 mol%) H2O

MeCN-CH2Cl2 rt

ẠY

KÈ

NaBH4 aq NaOH, rt

A032

A033

MeO MeO

CHO 1) NH2

MeO I MgSO4, CH2Cl2, rt

2) CF3CO2H, benzene reflux

O Me Me

Et2O, rt

Me H2SO4

OH O

IC IA L

MeO I

A034 POCl3

MeO

toluene reflux

MeO

MeO Me

MeO

N Me

IC IA L

A035 OH

aq NaOH

CHO

CHCl3, 60 C

CHO

MeO

CH2Cl2 -78 oC to rt

A037

HCl, NaNO2 H2O, 0 oC

NMe2 N

PhNMe2 0 oC

NH2

CO2H

ẠY

KÈ

CO2H

A038

H2C CH2 , AlCl3

Cl MeO

A036

Na, liq NH3

EtOH, Et2O -78 oC

A039

OMe CO2H

1) Na, liq NH3 THF, -78 oC C7H15Br -78 oC to rt 2) aq HCl ClCH2CH2Cl reflux

O C7H15

A040 CO2Me

NaH

NO2

THF 0 to 60 oC

CO2Me CO2Me

IC IA L

MeO2C

A041 PBr3

0 oC to rt

CrO3, H2SO4

(COCl)2 Me

CH2Cl2, -50 C;

Et3N -50 oC to rt

KÈ

CH2Cl2 -50 oC

O S

acetone-H2O rt

A043

A042

ẠY

A044

NaIO4 aq NaHCO3

OH O

CH2Cl2 rt

O CHO

A045 O

Me OH +

CO2Et

EtO2C N NCO2Et Ph3P Benzene rt

O O

CO2Et

A046 Me Me

aq H2SO4

reflux

IC IA L

A047 aq H2SO4

reflux

H2SO4

A048

A049 Me

KÈ

A050

ẠY

PhCN

OH Me Me

conc H2SO4

Me NC

Me Me

5 oC

N N CN e e M M ca t) AIBN , ( n-Bu3SnH benzene reflux

A051 HO

1) NaH, THF, CS2; MeI

H Ph

;

2) n-Bu3SnH, AIBN toluene, reflux

N O

H Ph

N O

A052 O

O K2CO3, reflux

IC IA L

H2N

2) H2NNH2, MeOH reflux

A053

N Ơ

2) aq H2O2 MeOH 3) heat 160 oC

1) HCHO, HCO2H H2O, reflux

NH2

M KÈ

O (mCPBA)

O H

A054

O O

CH2Cl2 rt

A055

O 85% H2SO4

ẠY

A056 O H OH

aq H2O2 NaOH H2O, 50 oC

OH OH

A057 MeO

NH2

MeO

NaOCl NaOH

MeO

H2O 50 oC

MeO

NH2

IC IA L

A058 O Ph

1) ClCO2Et, Et3N acetone, 0 oC; NaN3, H2O

2) toluene reflux

Me O

dioxane Et2O-H2O

A060

ẠY

KÈ

A061

H HO

Me Me

A059

NaOMe Et2O reflux

1) CHBr3, t-BuOK pentane -15 oC to rt 2) MeLi Et2O, -40 oC

OMe

A062 1) OH OMe

Br K2CO3 acetone, reflux

2) heat, reflux

OH OMe

CO2H

A063

TsOH (cat)

toluene,

IC IA L

A064 CO2Me

CO2Me

200 oC

CO2Me

A065 1) PhNHOH EtOH, rt

2) PhHC CH2 60 oC

N Ph

CHO

e O M O2C

A066

630 oC

12 mmHg

A067

ẠY

KÈ

O O O

o-C6H4Cl2 reflux

A068

Me OAc

SeO2 t-BuOOH H2O CH2Cl2 0 oC

Me OAc

A069 O

CH2

Ph3P CH2

IC IA L

Et2O reflux

A070 O Br

O (EtO)2P

(EtO)3P OEt

OEt

reflux

O (EtO)2P

O OEt

A071

NaH

benzene rt to 200 oC

OEt

A072 NH2

H2N

S 1)

H2O, 70 to 100 oC

2) aq NaOH, 45 oC

KÈ

A073

1) NaH, THF, 0 oC PhSeCl, 0 oC

A074 O

1) Me3SiCH2MgBr Et2O, reflux 2) NaH, THF reflux

O Me

2) aq H2O2 CH2Cl2, rt

ẠY

CH2

A075 Me

CO2Me

Pd(OAc)2 (cat) Ph3P (cat)

Me CO2Me

IC IA L

Et3N, 150 oC Me

Pd(OAc)2 (cat) Ph3P (cat) Na2CO3

Br + (HO)3B

n-PrOH-H2O reflux

OHC

A077 Pd(OAc)2 (cat) CuCl (cat), O2

OHC

A076

DMF-H2O, rt

A078

PCy3 Cl Ru Cl PCy3 Ph (cat)

ẠY

KÈ

Boc N

CH2Cl2 reflux

Boc N

ẠY M

KÈ Y

Q H

N Ơ N

IC IA L

ẠY M

KÈ Y

Q H

N Ơ N

IC IA L

Provide reasonable arrow-push mechanisms for following recations

H2O, reflux

NH2

IC IA L

f uming H2SO4 MeCN-hexane 0 oC to rt

H2O

-H+

O H2N

OH Me

+H+

N C Me

KÈ

OH O

OH2

NH2 -H+

+H+

N C Me

-H+

HO OH NH2

+H+

O H

-AcOH

ẠY

O HN OH

Me H2O

NH2

Jacobsen, E.N. Org. Synth, Coll. vol

2004. 29

Provide reasonable arrow-push mechanisms for following recations

B001 HO2C + MeNH2 +

CHO

MeN

H2O,

HO2C

B002 O

Al(i-OPr)3

i-PrOH reflux; aq HCl

NH2NH2 AcOH (cat)

B003 O

IC IA L

CHO

NaOH Na2HPO4 (pH 2.5-4.5)

EtOH, rt

B004

1) aqH2O2, K2CO3 MeOH, 0 oC to rt

Ar =

2) ArSO2NHNH2 CH2Cl2-AcOT, rt aq K2CO3

i-Pr

KÈ

B005

i-Pr

O NaCN (cat)

CHO

DMF 35 oC

ẠY

i-Pr

CN N

B006

Me N

Me O + O Me

S (cat) Et3N, EtOH 80 oC

O Me

Me O

B007 1) KOAc, Ac2O reflux O

CO2H

2) aq HCl, reflux

IC IA L

B008 O N H

KOH (cat) MeOH, reflux

aq HCl

benzene reflux

O Me

B009 LiOMe

CO2Me

+ MeO2C

OMe

MeOH reflux

CO2H

B010

Me Ph

ẠY

Et2O, rt

O OMe

KÈ

B011

H2C N N

OTs Li liq NH3

B012

CN Cl

NaNH2 liq NH3 -78 oC

B013 NaNO2 aq HCl, 0 oC

NH2

IC IA L

CuCl2 (trace CuCl) 0 oC to rt

DCC, TFA pyridine OH

O Me

DMSO, rt

H Me

B015

B014

B016

OTs

t-BuOK

t-BuOH 40 oC

H2O, 0 oC

aq HBr

KÈ

B017

n-Bu3SnH AIBN (cat)

Me Me

benzene reflux

ẠY

H Me

Me Me H

B018

O Ph

O O (cat)

CHCl3, reflux

CCl3

B019 O

Me Cl O o CH2Cl2, -7 C NH HCl

MeOH, reflux

IC IA L

Ph N

B020 C5H11

Me3SiI CH2Cl2, reflux

CO2Me

H N

C5H11

MeOH, rt

CO2Me

OMe

Pd(dba)2, (cat) dppb, Et2NH

THF, rt

EtO2C

B021

B022

NO2

PhSH KOH

KÈ

MeO

O O S N

CH3CN 50 oC

N H MeO

ẠY

B023

O BF3-Et2O O

Me Me

benzene

CHO Me

Me Me

B024

O Me S N O NO aq KOH, EtOH 10 to 20 oC

B025 NC Me Me

Me HMe

o-dichlorobenzene 180 oC

IC IA L

B026 O

CH2Cl2 0 oC

SiMe3

FeCl3

1) O2, hv acetone

B034

2) Et3N, CH2Cl2 reflux

B035

1) O2, hv acetone 2) Ph3P benzene

KÈ

B041

ẠY

PhCHO CrCl2 (2 eq) Br

OH Ph

THF, o 0 C to rt

B042

H2, CO HRhCO(PPh3)2 (cat) n-Bu

benzene, rt

CHO n-Bu

CHO

n-Bu

B045 S

KSCN Ph

dioxane-H2O 60 oC

IC IA L

O H Ph

B046 O Me

MeOH Me2N

OMe

N N H

NO2

2) Raney Ni, NH2NH2 THF-MeOH rt to 50 oC

OBn

1) Me2NCH(OMe)2 pyrrolidine DMF, 110 oC

B047

OBn

MeO

Me2NH (1.1 eq)

B048

O O S

Me (TosMIC)

t-BuOH, EtOH DME 5 to 40 oC

ẠY

KÈ

B049

1) CBr4 (1 eq) Ph3P (2 eq) CH2Cl2, 0 oC

O n-C7H15

2) n-BuLi (2 eq) THF, -78 oCto rt H2O

n-C7H15

B050 O

2) n-BuLi (2.2 eq) THF, -78 oC to rt benzophenone 0 oC to rt

Me Me

Ph Ph

Me Me

i-Pr Ar =

IC IA L

Me Me

1) ArSO2NHNH2 HCl, MeCN, rt

i-Pr

Me Me

CO2Na AcOH

MeOH-H2O 35 oC

NH OMe

CO2Me NH2

OMe

MeO

CO2Me

MeO

B051

i-Pr

B052

(HCHO)n K2CO3

Q M

KÈ ẠY

CO2Me

OH OH

N N (DABCO, cat)

O Me

MeOH reflux

B053

OH Me

heat, rt

CO2Me

B054

N H s T OH xylene reflux

CO2Me Et2O, rt

1) aq HCl 60 oC 2) H2, Pd/Al2O3 MeOH, rt

O CO2Me

B055 O S N3 O

Et3N OEt

MeCN rt

OEt N2

O H3N

2) aq HCl, rt

1) t-BuOK EtOH-toluene 0 oC to rt

B056

IC IA L

Br2 NaHCO3

CO2Et

EtOH-Et2O reflux

Et2O, 0oC

NaOEt

B057

B058

KÈ

CO2Me

KOH DMF, 60 oC

MeI, rt

MeCN-H2O rt

O O

OMe

ẠY

B059

H2C N N , 2 eq Et2O, rt

MeO2C

O MeO2C

HBr

B060 CO2H N Me

Ac2O reflux

N Me

B061

OH + H2N

CO2t-Bu

Et3N DMF, rt

OH O

H N

Me 11

OH O

B062 PCl5 POCl3 100 oC

B063 O OMe

CH2Cl2

DDQ

N O

NH2

OMe

B064

KÈ

OMe

O Cl S N C O O (CSI) toluene, rt

CN OMe

2) DMF, rt OMe

ẠY

OMe

B065

NC CO2H NH2

O Br t-BuNO, H2O ClCH2CH2Cl reflux

N H

CO2t-Bu

IC IA L

O EtO P EtO CN

B066 OH 1) PhI(OAc)2 CF3CH2OH 2) NaHCO3 MeOH

N Cbz

CO2Me

OH NHCbz

IC IA L

B067 MeO2C

CH2Cl2

cyclohexane CH2Cl2, rt

MeO2C

Me TfOH (cat)

N Y

B068

CO2H

t-BuOH, HCO2H H2SO4 CCl4, rt

KÈ

B069

ẠY

n-BuLi

Et2O, rt

B070

Ph Ph

CO2Me

N NaH

DMF-dioxane rt

CO2Me O

OBn Me

DBU (cat) Cl3CCN

B071 S

N n-Bu3SnH AIBN (cat)

O O

IC IA L

benzene, reflux OH Me

CH2Cl2, -15 oC H

t-BuOK

Me SO2CH2Br

t-BuOH-THF 0 oC to rt

B073

O O S

B072

KNH2 hv

THF, rt

B074

KÈ

hv BF3-Et2O THF, rt

ẠY

Bu N

N S

B075

Me Me

1) CHBr3, t-BuOK petroleum ether 0 oC t o r t 2) MeLi Et2O, 0 oC to rt

Me Me

B076 O Cl3C

OEt

NaOMe petroleum ether 0 oC to rt

IC IA L

B077

2) MeLi, THF, -10 oC H3O+

CHO

1) Cl3CCO2H, Cl3CCO2Na DMF, rt; Ac2O, rt Zn, AcOH, 60 oC

B078

SiMe3

BnNH2 aq HCHO TFA

H2O, 25 oC

NBn

B079

KÈ

Me Me

Me H

O O S HN NH2 NO2 EtO2C N N CO2Et Ph3P, NMM -30 oC to rt

ẠY

Me Me Me

Me H

N H

CO2Et

B080

CHO

1) Ph3P CHCO2Et benzene, reflux

NO2

2) (EtO)3P 170 oC

B081 NaNO2

CO2H H Me

aq HCl rt

CO2H H Me

IC IA L

H2N

B082 MeO

NaNO2 A NH2

aq HCl, 0 oC

CO2Et

B083

(C6H13)3B

KÈ

B084

THF-H2O reflux

ẠY

O C6H13

I2, AgNO3 HC(OMe)3 MeOH reflux; H2O

i-Bu

OMe O

i-Bu

B085

N H

2) aq HCl, EtOH 65 oC

MeO

1) KOH, EtOH-H2O A 0 oC

H2SO4 Me

Ac2O -20 oC to rt

O SO3H

B086 OMs Me

B2H6, THF

IC IA L

aq NaOH reflux

B087 1) Br2, CHCl3-CH2Cl2 0 oC

2) t-BuOK, Et2O 65 oC

B088

toluene MS 4A reflux

N N

N H

B089

CH2Cl2 0 oC

KÈ

N O

aq NaOCl Et3N

ẠY

B090

AcO

O2N

PhN C O (2eq) Et3N benzene rt to 80 oC

AcO

B091 CH3C(OMe)3 EtCO2H (cat)

138 oC

HO Me

Me EtO2C Me

B092 O Me

PhCHO CSA N H Me OMe

benzene reflux

IC IA L

B093

2) toluene, 110 oC; 1 N HCl, THF, rt

OMe

NaH THF rt

O S

B094

decalin 150 oC

CHO

ẠY

KÈ

B095

OMe

HO2C

1) TBSOTf , Et3N CH2Cl2 -78 to 0 oC

1) 1,3-dithiane, 20 oC 2) n-BuLi, THF -78 oC 3) HgCl2, MeCN-H2O reflux

CHO

B096

H N

CO2Et

CHO

K2CO3

DMF 20 oC

toluene reflux Dean-Stark trap

CO2Et

Me H

N H O

B097

Me H Me OH

2) hv , benzene, rt 3) THF-i-PrOH reflux

OAc

NO2

CCl4, rt

H Me OH

AcO

B098 O

IC IA L

AcO

NOH

1) NaOCl, pyridine -78 oC

B099

O Me P(OEt)2 n-BuLi

THF -78 oC

PPh3 Br NaH CHO N H

Et2O reflux

ẠY

KÈ

B100

B101 N3 Ph

Ph OH

Ph3P

toluene reflux

H N

H Ph

OAc

B102 Ph3P Se TFA

H Ph

CH2Cl2, rt

IC IA L

H Ph

B103 1) N OH

toluene, reflux Ph

2) (MeO)3P reflux

B104 O

C8H17

CCl4, rt

C8H17

Me3SiI (2 eq)

B105

OMOM C6H13

KÈ

H Si Me Me

ẠY

1) Pt[(H2C=CHSiMe2)2O]2 toluene, 60 oC

OMOM C6H13

2) 30% H2O2, aq KOH MeOH-THF, rt

OH OH

B106

Me Me

Me OH Me

PhSCl Et3N CH2Cl2 -78 oC to rt

Me Me

Me SPh O

B107 O SmI2 (4 eq)

THF-HMPA 0 oC to rt

O Me

IC IA L

MeO Me

B108 MeO Me

OMe

MeO Me

MeNO2 0 oC

Hg(OTf )2 (1% mol)

OMe

H Me

B109

PCy3 Cl Ru Cl PCy3 Ph (cat)

CH2Cl2 reflux

MeO2C

SMe2 I NaH

B110

KÈ

CHO

N H

THF, 0 oC

NaN3

N3 N

H2O, 0 oC

ẠY

B111

TfOH

O Me

O CH2Cl2 0 oC

(n = 1)

O n

TfOH CH2Cl2 0 oC

Me NHPh

(n = 3)

B112 O O S Tol S

Et3N

aq HCl

MeCN, reflux

50 oC

B113

t-BuOH-DMF rt

O Me

Me N Me

THF, 0 oC

toluene reflux

CO2H

CSA (0.1 eq)

OSiMe3

CO2Et

toluene reflux

OSiMe3

M CO2Et

Na (4eq) Me3SiCl (4 eq)

KÈ ẠY

NAc

B114

B115

NAc

AcN

t-BuOK PhCHO

IC IA L

O O S Tol S

B116

O3 MeOH-CH2Cl2 -78 oC; TsOH -78 oC to rt NaHCO3 neu tralize); ( Me2S

OMe MeO

CHO

B117 O3 e M OH-CH2Cl2 -78 oC;

OMe CHO

IC IA L

evaporation; Ac2O, Et3N 0 oC

n-Bu3SnCl (cat) NaBH3CN AIBN, t-BuNC

OEt O

OEt

B118

t-BuOH, reflux

BF3-Et2O

B119

CH2Cl2, rt

B120

KÈ

N O

CH2Cl2 rt

ẠY

NOH

NMO, Et3N

B121

decalin 290 oC

B122 Me

1) CH2N2, Et3N Et2O, 0 oC

O SO2Cl

2) 95 oC

IC IA L

B123

PPh3Br

t-BuOK

THF, rt

B124

1) CHCl3, reflux 2) PhSeCl, CH2Cl2 -78 oC

OTBS

O Me

O H

3) aq H2O2, THF 0 oC

KÈ

B125

1) ClCH2COPh, K2CO3 THF, rt

ẠY

2) hv , cyclopentadiene CH2Cl2, rt

B126

AcO

O Me N2

rhodium(II) mandelate CH2Cl2 reflux

AcO Me O

B127 OMe Ph

OMe

Ph Cr(CO)3 Ph

n-Bu2O 45 oC

Ti(Oi-Pr)4 (cat) EtMgBr (2 eq)

O OMe

Et2O, rt

ẠY

KÈ

B128

IC IA L

Cr(CO)5

ẠY M

KÈ Y

Q H

N Ơ N

IC IA L

ẠY M

KÈ Y

Q H

N Ơ N

IC IA L

Provide reasonable arrow-push mechanisms for following recations

Hg(OAc)2 AcOH, 70-75 oC

CO2Me

MeO2C CO2Me benzene, reflux

CO2Me

AcO

OAc

IC IA L

OAc

AcO

MeO2C

Y Q

HgOAc

OAc

AcO AcO

KÈ

Hg OAc

ẠY D

CO2Me CO2Me

CO2Me

AcO

OAc Hg OAc

Me CO2Me

H O

OAc CO2Me

AcO + AcO

O H AcO

OAc

Noller, C. R;Dinsmore, R. Org. Synth. Coll. vol

1943. 358

Provide reasonable arrow-push mechanisms for following recations

C001 O MeOH, rt

Me H

t-Bu

Me H

t-Bu

C002 SO2 NH2

O2N O

Et3N, THF reflux

MeO

NO2

IC IA L

OMs

MeO OMe OH

NaOMe

C003

TiCl4

MgBr THF, 0 oC

heat, 200 oC

CH2Cl2 -78 oC

Et Me O

ẠY

KÈ

C004

C005

1) TfOH, CH2Cl2, 0 oC

EtO2C

SiPh3

Me pyridine 2) toluene, reflux 3) TBAF, H2O2 DMF, 55 oC

OH Me

CO2Et OH OH

C006

O O

1) TsNHNH2 Et2O

2) NaH DMF, 120 oC

N Ts

IC IA L

NHTs

C007

CHO

t-Bu N C Ph

toluene -30 oC to rt

NH2

H N

O Me

Ph CO2H

OBn

C008

U OMe

OMe OMe

toluene 110 oC

OH O O

BnO

HO O

OMe OMe

ẠY

C009

KÈ

F3C + F

KOH

N O

dioxane, rt H2O

O HO2C CF3 Ph NH O

C010 PhI Pd(OAc)2 (cat) NaOAc, LiCl DMF, 100 oC

t-Bu

C011 MeO2C

IC IA L

PhCl 190 oC

CO2Me

C012

Ac2O

N H

85 oC

N H

OAc

C013

1) t-BuOOH, VO(acac)2 CH2Cl2, -30 oC

OMEM Me Me

OHC

MEMO

2) toluene, 110 C

H MeMe

Q KÈ

C014

1) NOCl o pyridine, 0 C

ẠY

2) hv , pyridine 3) TsCl, pyridine benzene, rt

C015 O Me

O N2

1) Rh(OAc)2 (cat) CH2Cl2 2) SmI2 THF, 50 oC

C016 N2 1) Me3Si BuLi, DME-hexane

Me O

2) silica gel

C017

3) Ca(OCl)2 CH2Cl2-H2O, 10 oC 4) aq HCl THF-H2O, rt

N Tr

NH2

N Tr

1) H2C CHMgBr THF, -10 oC 2) DBU, Cl3CCN CH2Cl2, rt

IC IA L

1) EtMgBr, THF-H2O

2) benzene, reflux

OMe OH Me

OMe

1) TsNH2, BF3-Et2O benzene, reflux

O H

Ts N

CO2Et Ph3P (cat) benzene, reflux

Ph CO2Me

C020 CO2Et TBSO

Ti(OPr)4 i-PrMgCl (2 eq)

1) FeCl3 pyridine, DMF

Et2O

2) NaOAc, MeOH

TBSO

Me Me

M KÈ Ph

ẠY

C019

OMe

MeO

C018

C021 Me Me N Li Me Me

n-BuLi

IC IA L

Et2O-hexane

Et2O

C022

CO2H

1) pyrrolidine toluene, reflux 2) (PhO)2P(O)N3 toluene rt then reflux

3) KOH ethylene glycol reflux

C023

Q CO2Me

KÈ

TMS

1) LiI, EtOAc reflux 2) Ac2O 70 to 125 oC

ẠY

C024

1) PhSeBr, i-Pr2NEt MeCN, 0 oC

Me O

2) NaIO4, NaHCO3 MeOH-H2O, rt 3) hexylamine, MgSO4 toluene, reflux

Me O O

C025 O HgCl2

AcO

H2O-caetone reflux

BnO

OMe

OBn

C026

1) LiO-i-Pr (cat) Et2O, rt

O Me

OH OH Ph

2) NaOH, MeOH reflux

IC IA L

AcO

BF3-Et2O ethylene glycol

O Me

CH2Cl2, 20 oC

C027

C028

MeN

MeO

KÈ

Me Me

2,6-lutidine toluene, rt

3) MsCl, Et3N CH2Cl2, -78 oC 4) t-BuOK THF, reflux

ẠY

1) MeAlCl2 CHCl3, rt 2) NaBH4 MeOH, 0 oC

NMe MeO Me

C029

BH2

Et2O -20 oC

1) CH3CHO Et2O, 0 oC 2) Cl2CHOCH3 t-BuOLi, Et2O 0 oC to rt 3) H2O2, NaOAc H2O, reflux

C030 PhNC Me3SnSnMe3 hv

N I

benzene 20 oC

OH O

Et HO

C031 O

O N

IC IA L

OH Me

N Ơ

PhNEt2 230 oC

C032

Me Me

N C N benzene, reflux;

KÈ

ẠY

C033

n-BuLi, THF -78 oC;

n-BuLi (1 eq) THF, -78 oC;

PhSCl -50 to 0 oC

HO OHMe Me

OHMeCHO O

O H (0.4 eq) aq NH4Cl, rt

Me Me

O H

H O Me Me

S O

C034 OTBS

PCy3 Cl Ru Cl PCy3 Ph (cat)

IC IA L

OTBS

benzene rt, 4h

C035

OBoc

OEt

Et2O -78 oC to rt

OBoc

PhMgBr

OEt

OBoc

C036

BnO BnO

NBS MeOH CH3CN

OBn O

BnO BnO

OBn

OMe

OBn

KÈ

C037

ẠY

Et2O -78 to 20 oC

H2O

Me Me

Me Cl Me HgCl2 (cat)

C038 O H

1) N3CH2CO2Me NaOH, MeOH, rt 2) cyclohezane, reflux 3) p-xylene, reflux

N H

CO2Me

C039 OLi 1) Li Me Et2O -78 oC to rt

2) H2SO4 MeOH 0 oC

Me Me

C040 Me

OMe

PhI(OCOCF3)2

mesytilene 200 oC

O e OM O

THF rt

Me Me

IC IA L

C041

hv NaBH4

MeO N

MeO

MeOH 5 to 10 oC

O H

KÈ

C042

TMS

LDA

ẠY

O TBSO

TBS

THF, -80 oC

(CH2)4CH3

THF -80 to 30 oC

TMS

C043

Me H

SmI2 HMPA t-BuOH THF 0 oC

HO Me H

H O

(CH2)4CH3

C044 O Me

NaOMe

H H

MeOH reflux

OTs

IC IA L

Me O

MeO

Me Me O

O O (Meldum's acid)

MeO

H2NCH2CH2NH2 2AcOH (cat) Na2SO4, MeCN, 20 oC reflux

C045 Me

OEt

Y U Q M OMe

KÈ Me

N N

ẠY

Br Br

C046

t-BuLi (4 eq), THF -78 to 0 oC

OH Me CO2Et

-78 oC

MeO2C

CO2Me

H toluene reflux

OMe

C047

1) NaH, Me DMF, 60 oC 2) LiAlH4, AlCl3 Et2O, 0 oC

MeO

O N H

CH2 Br

3) mCPBA, CH2Cl2, rt KCN (excess) DMF-H2O, 50 oC

MeO

CN N Ph

C048 1) O S N CO2Me benzene, 0 oC 2) PhMgBr THF, -60 oC

3) (Me2N)3P -78 oC

IC IA L

NH O

2) O3, CH2Cl2, rt 3) H2, Pd/C, EtOH, rt

Me Me OH

OMe

Me Me OH

CH2Cl2, rt

OMe

O Br

H2N

OMe

N H

ẠY

KÈ

CO2H

Ph3P CHCN EDCI

OMe

benzene, 0 oC PhMgBr THF, -60 oC

C050

C051

1) LDA, TBSCl HMPA, THF

C049

1) O

AcCl toluene, reflux

NH2 CO2Et

2) NaBH4, H2SO4 EtOH, -30 oC 3) Me3SiCH2MgCl (2 eq) CeCl3, THF; aq HCl

O Pr

H N

C052

CO2H

3) MeLi, THF, -78 oC 4) Mn(OAc3), Cu(OAc)2 EtOH, rt

IC IA L

1) (COCl)2, benzene 2) Et3N, toluene, reflux Me

C053 TMSOTf (0.5 eq) MS 4A

CHO

OH Ph

CH2Cl2 -78 oC

SiMe3

O O

Q M

C055

KÈ

H N

Ts n-BuLi (1 eq)

OSii-Pr3

Ph Ts Me N

OTf Me

ẠY

hv ClCH2CH2Cl rt to reflux

i-Pr3SiCl

OSii-Pr3

LiCHBr2, THF n-BuLi (2 eq) -78 to 25 oC

C054

Ph THF, reflux

C056

OBn

O OHC

1) NH3, CH2Cl2, 0 oC 2) NH4OAc, AcOH, 75 oC

C057 H2 Lindlar catalyst quinoline CH2Cl2-MeOH 25 oC

IC IA L

H H OH

Tol

Zn(Cu) Cl3CCOCl

C058

O STol N(Boc)2

Ơ H N

C059

KÈ

AlCl3

MeO

Me Me

CH2Cl2 0 oC

S Me Me

MeO

ẠY

C060

THF, -45 oC

N(Boc)2

1) Pd2(dba)3-CHCl3 (2.5 mol%) DPPE, MECOCH2CO2Me THF, rt 2) silica gel

Me O Me

O OMe Me

C061 Me

MeCN 130 oC

IC IA L

Pd(OAc)2 Ph3P, Ag2CO3

Me3Si OH

TsOH decalin 175 oC

CH2Cl2 -78 oC

H OH

benzene

EtAlCl2

C062

2) activated Zn i-PrOH-H2O reflux

O Me

OH O

BzO Me

1) NBS, BaCO3 CHCl3, reflux

OMe OH

C063

n-BuLi 330 oC

N NHTs

ẠY

KÈ

C064

C065

NO2 SiMe3 TBSO

SO2NHNH2 DEAD, Ph3P

THF -15 oC to rt

SiMe3 TBSO

C H

C066 BrMg (excess) Me

N H

IC IA L

THF -40 oC

NO2

C067

CH2Cl2, rt

TiCl4-(THF)2 (cat) i-Pr2NEt

sy n : anti = >99 : 1

C068

1) Zn(Cu), Cl3CCOCl Et2O, reflux 2) Zn, HOAc, 85 oC S

3) HF, MeCN-H2O, 20 oC 4) CSA, hexane-CH2Cl2,

TBSO

C069

N Bn

ẠY

KÈ

(OC)4Cr

OMe

1) ZnCl2, hv CO, THF

H I

2) I2, MeCN, rt

Me OMe

C070

Me Me OH OH

1) ClOC OAc e (2 q) e M CN

OH OH OH

2) NaOMe, THF

O OH

C071

NHBn

BF3-Et2O toluene, reflux

IC IA L

MS4A

CO2Me

N H

NBn

CHO

N H

CO2Me

C072

3) mCPBA, CH2Cl2, 4) MeOH, heat 5) H2, Pd/C, MeOH

N H

1) H2C CHCN MeOH 2) H2C CHCH2Br NaH, THF

C073

MeLi (cat) Ph2O, 180 oC

TBAF

TMS

C074

KÈ

1) NaOH, THF, rt S

N H

2) Rh2(OAc)4 benzene, reflux 3) Raney Ni, acetone

ẠY

C075 O Me

OMe N2

1) Rh2(OAc)4 benzene, reflux

O +

2) BF3-Et2O benzene, rt

Me H HO MeO

Me O

C076 1) LiSnMe3, THF O Me , BF3-Et2O o -78 C

IC IA L

O 2) Pb(OAc)4, CaCO3 benzene, reflux 3) H2, (Ph3P)3RhCl

C077 H

n-BuLi

THF, -85 oC Me

1) C6H11NHOH, NaHCO3 EtOH, rt

O O Me

OAc Me

C079

KÈ

OTBS Me

ẠY

HO O

OTBS

1) O2, hv rose bengal MeOH-CH2Cl2 Me2S 2) Ac2O, Et3N DMAp, CH2Cl2 3) DBU, toluene 110 oC

TBSO H O OTBS O

C080 O

O Cl

Et3N benzene reflux

hv CH2Cl2 O

Me Me

2) AcCl, Et3N, Et2O, 0 oC to rt 3) NaOAc, AcOH, rt

O O Me

OHC

CHO Me

C078

C081 O

O TiCl4

SiMe3 +

SiMe3

CH2Cl2 -75 to 0 oC

Me Me

C082

O Ph

Ph2PCl, 0 oC

Ơ N

MeO

1) KHDMS Et2O

OMe

MeO

2) O3, CH2Cl2 -78 oC; Ph3P TsOH benzene

BnO

KÈ N

ẠY

N Ns

O Et

PhCO2H CH2Cl2, rt

C083

C084

Et OH

n-BuLi THF, 0 oC

IC IA L

Bn N C CO2H MeOH rt

toluene reflux

NHBn N Bn

NsHN O

C085

Me Me

O H

THF -70 oC to rt

SOCl2

Mg Et2O, rt; 60 oC

Et2O rt

H2C CHCHO -10 oC to rt

Me OH Me

MeH

C086 O P Ph Ph Ph

t-BuOK, THF, rt; ClO4

CO2Et

Ph Ph

EtO

IC IA L

reflux

CO, Pd(PPh3)4 K2CO3, n-Bu4NBr

C087

MeCN, 70-80 oC

N Ts

C088 Li SPh

Et2O, rt

THF, rt OH

THF 0 oC

LiBH(s-Bu)3 MeLi, KOEt

HBF4

NHTs

C089

Boc N

ẠY

KÈ

1) LDA, Et2O 0 oC NBoc

2) KH, CS2; MeI THF, 0 oC 3) n-Bu3SnH, AIBN toluene, 100 oC

C090

O MeN

N H

Me N

HO N

(HCHO)n Na2SO4 O

NMe

NMe N N

MeCN reflux O

C091 Ph O

SnCl4, CH2Cl2, -78 oC

NaHCO3

NiCl2/NaBH4

benzene reflux

EtOH, rt

H2N Me

C092

Et2O -78 oC

dioxane 0 oC

BF3-Et2O H2O

BnO

Et3N

BnO

C093

O Me4N CH2Cl2, 0 C

Tf 2O pyridine

CH2Cl2 0 oC

M KÈ

C094

ẠY

2) benzene, 65 oC

EtO2C

(OC)5Mo

ClSN Me

IC IA L

NO2

Me Me

1) t-BuOK, t-BuOH -5 oC to rt 2) O3, NaHCO3 MeOH-CH2Cl2, -70 oC

Me CO2Me

3) Ac2O, Et3N, DMAP benzene reflux

Me Me

C095 Me H

Me O

H TMSOTf toluene rt

Me CO2Et

H Me

OSiMe3

C096 1) PhLi, Et2O; H3O+

H O

O OH

2) TsOH, H2O CH2Cl2

IC IA L

MeO

C097 1) Br2, CHCl3, rt 2) AgNO3, MeOH reflux

CO2Me

Me3Si

CO2Me

3) TFAA, DMSO CH2Cl2 -78 oC to rt

CO2Me

C098

1) NH2OH-HCl NaOAc MeOH, rt

N O

2) sealed tube toluene, 160 oC

C099

TBS

KÈ

TBS

SPh2 BF4 KOH, DMSO aq BF4, Et2O, rt

2) PhSSPh (excess) NaOMe, MeOH,

O PhS PhS

O O H

ẠY

C100

OTs CO2t-Bu N Boc

S CO2Me 1) Cl pyridine, CH2Cl2 2) mCPBA (2 eq) CH2Cl2 3) KOMe, THF-MeOH 4) SmI2, THF-MeOH

CO2Me CO2t-Bu N oc B

C101 OMe S

toluene

IC IA L

OMe

OSiMe3

BF3-Et2O CH2Cl2, -75 oC

OSiMe3

CH3CO2H -75 oC to rt

EtO OEt

C102

1) NH2OH-HCl NaOAc, MeOH, rt 2) NaBH3CN, MeOH, rt

3) (HCHO)n, MS4A toluene, reflux 4) MeOSO2F, ether, 0 oC LiAlH4, THF, rt

Me H N

C103

KÈ

C104

CO2Et

MeO

CO2H

reflux

ẠY

MeO

Ac2O (10 eq) NaOAc (2eq)

AcO

CO2Et

MeO OAc

MeO

C105

Me Me O Me

1) hv acetone

O O

2) H2, Pd/C MeOH, rt

H H

H Me Me O

C106 H

Ph Ph

N N

toluene 110 oC

IC IA L

Ph H

C107 210 oC

quinoline

Cl Cl

C108

1) KH (excess) 18-crown-6, THf , rt ClCO2Me (excess) o pyridine, -78 C to rt

2) KOH, MeOH-H2O, rt

OMe

ẠY

KÈ

TBSO

C109

1) mCPBA, CH2Cl2, 0 oC 2) aq HBF4, CH2Cl2, rt

Me TBSO

Me ,CeCl3 3) BrMg THF, -78 oC to rt 4) PdCl2(MeCN)2 (1 eq) DME, rt

Me O

ẠY M

KÈ Y

Q H

N Ơ N

IC IA L

A001 O O2N

OH O

O OH O2N

OMe

O2N

OMe

H C

O2N

aq HCl O2N

O2N

IC IA L

Kamm, O.; Segur, J. B. Org. Synth. Coll. Vol.

1941, 391

A: Addition of hydroxide ion to the carbony group to form a tetrahedral intermediate. B : Elimination of

methoxide ion helped by the oxygen lone pair. C: Deprotonation. pKa AcOH = 4.8, H2 O = 15.7. +

Protonation on work-up. pKa H 3O = -1.7.

A002

H HO O Et

HO OEt

-H+

EtOH

OH2

KÈ

HO OEt

O +

-H2O

OEt

-H

OEt

Fischer, E.; Speier, A. Ber. Deut. Chem. Ges. 1895, 28, 3252

A: Acti vation of the carbonyl group by protonation. B: Additiono f EtOH to the activated carbony group.

ẠY

C: Deprotonation of the oxonium ion. D: Protonation makes a hydroxy group a good leaving group.

E: Elimination of water helped by the oxygen lone pair. F: Deprotonation

A003

O Me

Cl OH

O S

Cl A

O S

O Cl Me

S O

Cl H

-SO2 Me

-H+

O Me

O S

Cl H

O S

O Cl

O S

IC IA L

Helferich, B.; Schaefer, W. Org. Synth., Coll Vol

1941, 147.

A : Atack of a carboxylic acid to SOCl 2 forms a mixed anhydride. B: Addition of chloride ion to the

carbonyl group to form a tetrahedral intermediate. C: Formation of an acylium ion. D: Addition of

chloride ion to the acylium ion

A004 O

O Ph

OEt

BrMg

OEt

O -EtOMgBr B

KÈ Ph Ph

ẠY

O MgBr

Ph MgBr

aq NH4Cl

Ph Ph Me

Allen, C. F. H.; Converse, S. Org. Synth., Coll. Vol.

1941, 226.

A: Addition of PhMgBr to the carbonyl group of the ester to form a tetrahedral intermediate. B: Elimi-

nation of ethoxide ion to form a ketone. C: Addition of PhMgBr to the more reactive ketone to form a tertiary alkoxide.

A005

MeO

N MeO

aq H2SO4

MeO

Ph MgBr

MeO

H H2N O H e M O Ph

H Ph

-H+

+H+

MeO

H -H+ Ph

MeO

H3N OH MeO Ph

H2O

H2N OH e M O Ph

IC IA L

1955, 562.

Moffett, R. B.; Shriner, R. L Org. Synth., Coll Vol.

A: Addition of PhMgBr to the nitrile forms an imine anion, B: Addition of water to the iminium ion gives

a hemiaminal. C: Protonation occurs on a more basic amino group. pKa H3O+ = -1.7, EtNH3+ = 10.6.

D: Elimination of ammonia helped by the oxygen lone pair. E: Deprotonation.

A006 Me

MgBr

KÈ

ẠY

N Me

H O MgBr Me N Me

N Me

OH H N Me Me

H O aq HCl

Me N Me

H H

O -H+

Olah, G. A; Surya Prakash, G. K.; Arvanaghi, M. Synthesis 1984, 228

A: Addition of PhMgBr to the carbonyl group. The resulting tetrahedral intermediate is relatively stable because the alkoxide anion cannot generate an amine anion ( pKa i-PrOH = 17, Et2NH = 36). B: +

Protonation on workup. C: Protonation of a more basic amino group. pKa H3O = -1.7, EtNH 3 =

10.6. D: Elimination of the amine helped by the oxygen lone pair E: Deprotonation.

A007 O

R' N C N

N C N R' H

EtO2C

Me Me

R H O

Me Me Me

O R

Me N Me N

Me Me Me

N H

Me R' N N Me H

R' NH

N R'

R' NH

N O

N R'

IC IA L

Me N Me

O OEt

-DMAP F

Me R O

Me Me

Me N Me

Me Me

O Me

O 1990, 93.

Neises, B.; Steglich, W. Org. Synth., Coll. Vol.

A: Acti vation of DCC b y protonation. B: Addition of the carbo xylate to the protonated DCC. C:

KÈ

Addition of DMAP to the carbonyl group. D: Elimination of a urea anion which then abstracts a proton from an alcohol.

E: Addition of the alkoxide anion to the carbonyl group to form a tetrahedral

ẠY

intermediate. F: Elimination of DMAP to form the product.

A008

O A

HO H HO O

H -H+ C

HO O

HO +H+ H2O O

-H2O

-H+

O H

E Daignault, R. A.; Eliel, E. L Org. Synth., Coll Vol.

1973, 303.

IC IA L

A: Activation of the carbonyl group by protonation. B: Addition of ethylene glycol to the activated carbonyl group. C: Proton transfer. D: Elimination of water helped by the o xygen lone pair. E:

Intramolecular addition of the second hydroxy group.

A009 O

H A

BnO OH

MeOH

H2O OMe

+H+

-H2O

BnO

BnO OH

KÈ

H MeO O Me H

ẠY

BnO

OMe

OMe -H

OMe BnO OH

H e M O O Me -MeOH

MeO OMe F

MeOH

Me H

BnO

-H+

BnO

HO OMe

H HO O Me

OMe

OMe H

OMe H2O

OMe H G

O H

OMe

-H

OMe

Me -MeOH OMe

H H

OMe

-H+

OMe

Baker, R.; Cooke, N. G.; Humphrey, G. R.; Wright, S. H. B.; Hirshfield, J. J. Chem. Soc., Chem. Commun. 1987, 1102.

IC IA L

A: Acti vation of the carbonyl group by protonation. B: Addition of MeOH to the activated carbonyl

group. C: Proton transfer. D: Elimination of water helped by the oxygen lone pair. E: Addition of MeOH and protonation to form a dimethyl acetal. F: Trimethyl orthoformate serves as a scavenger of water to let the equilibrium to the product side. Protonation followed by elimination of MeOH.

Addition of water. H: Proton transfer. I: Elimination of MeOH followed by deprotonation to form

HCO2Me.

H O

O H

Br Br

-HBr

O H Br

OH Br

-HBr Br

A010

Aben, R. W. M.; Hanneman, E. J. M.; Scheeren, J. M. Syn. Commun. 1980, 10, 821. A: Protonation. B: Cleavage of the dioxolane ring helped by the oxygen lone pair. C: Deprotonation

KÈ

to form an enol ether. D: Bromination of the electron-rich enol ether. E: Intramolecular addition of the hydroxy group.

Opening of the dioxolane ring of the product is more difficult because of the

ẠY

electron-withdrawing bromine atom.

A011

O Me

O A

H HO NH2

H H NH3

H +

-H

HO NH2 Me

+H+ C

NH2

H2O NH2 -H O 2 Me

N H2N C aq HCl

N H H3N C

-H+

OH2

O H

OH +H+

+H+ J

OH OH2

-H+

H3N CO2H

O H

-NH3

H3N OH

-H+

+H+

O H

H H2N OH

NH2

IC IA L

R C N H

-H+

Kendall, E. C.; McKenzie, B F. Org. Synth., Coll. Vol.

1941, 21

Strecker amino acid synthesis, A: Protonation of the carbonyl group. B: Addition of NH3 to the carbenyl group followed by deprotonation to form a hemiaminal.

C: Protonation followed by

elimination of water is helped by the nitrogen lone pair to form an iminium ion. D: Addition of a cyanide ion to form an aminonitrile. E: Acidic hydrolysis of the nitrile. The amino group is protonated

throughout the reaction. F: Protonation of the nitrile to form a reactive nitrilium ion. G: Addition of

water to the nitrilium ion. H: Deprotonation and tautemerization. I: Protonation of the resulting amide

followed by addition of water. J: Proton transfer. K: Elimination of NH 3 followed by deprotonation to

form theproduct.

KÈ

A012

O Me

ẠY

O Cl P Cl Cl

N Me

O P Cl O Cl Me H N Me

Cl H Me2N

N Me

Me2N

O P Cl O Cl Cl Me H N Me

Cl Me N Me

-H

Me2N

Me N Me

OH R

H2O

N Me

H +H+ Me

N Me

Me N H Me

-H+

N Me

IC IA L

H2O

-H+

H Me2N

1963, 331

Campaigne, E.; Archer, W. L. Org. Synth., Coll. Vol.

Vilsmeier reaction. A: The electron-rich oxygen of D MF attacks POCl 3 (oxygen of amides is generally more reactive toward electrophiles under neutral conditions). B: Addition of chloride ion followed by

E: Addition of water to the iminium ion.

nitrogen lone pair leads to the formation of an iminium ion F: Proton transfer followed by elimination of Me 2NH.

D: Elimination of chloride ion helped by

aromatic ring to Vilsmeier reagent followed by rearomatizatien

eation of a dichlorophosphate ion to form the Vilsmeier reagent. C: Addition of an electron-rich

A013 H

H e M 2N OH

H H

-H+

KÈ

Me2N OH

ẠY

Me2N OH2

+H+

Me -H2O

Me H

Me O

-H+

Me H

C H

O NMe2

-H+

O NMe2

Maxwell, C. E. Org Synth., Coll. Vol.

1955, 305.

Mannich reactien. A: Protonation of formaldehyde followed by addition of Me 2NH to the carbonyl group. B: Proton transfer followed by elimination of water to form an iminium ion. C: Tautomerization of the carbonyl goroup to form an enol. D: Attack of the electron-rich enol to the iminium ion.

A MeO

-H+

+H+

Ac2O

H Me O O

-H+

MeO

-H2O

+H+ B

NH2OH

H H2O N OH

HO NHOH

-H+

MeO

H O NHOH

IC IA L

A014

MeO Buck, J. S,; Ide, W. S. Org. Synth., Coll Vol.

1943, 622

A: Addition of NH 2OH to the aldehyde. B: Proton transfer followed by elimination of water to form an

KÈ

oxime. C: Acetylation of the oxime. D: syn-Elimination of AcOH to form a nitrile.

ẠY

A015

N OH OMe

PCl4 Cl

H N O PCl4 A

OMe

CN OMe

-H+

OMe

Cl -POCl3

Cl N O PCl3

OMe

H2O

H OMe

OMe

O H

OH2

-MeOH R

-H+

Me OH

IC IA L

-H

OMe

Ohno, M.; Naruse, N.; Terasawa, I. Org. Synth., Coll. Vol.

1973, 266

Beckmann fragmentation. A: Attack of the oxime to PCI5. B: Elimination of POCl 3 is helped by the oxygen lone pair of the methoxy group, causing the cleavage of the C-C bond. C: Addition of chloride

ion. D: Elimination of chloride ion followed by addition of water. E: Proton transfer followed by

elimination of MeOH.

O MgBr aq H2SO4 EtO Me

EtO

Me MgBr

+H+

EtO

H2O

M KÈ ẠY D

H EtO HO

H EtO O H

EtO

OH2 Me

OH Me

EtO

O Me

EtO

A016

H Me

-H+

EtO HO

-H+

-EtOH

-H+

Woods, G. F.; Griswold, P. H., Jr.; Armbrecht, B. H.; Blumenthal, D. I.' Plapinger, R J. Am. Chem. Soc. 1949, 71, 2028 A: 1,2-Addition of MeMgBr to the carbonyl group. B: Protonation followed by elimination of water helped by the oxygen lone pair of the ethoxy group. C: Addition of water. D: Proton transfer followed by elimination of EtOH.

A017 Me

H H N NH2 O Me H OR Me

Me O Me

A Me

N H

-H2O

+H+ B

H OR

Me -N2

H N H N

D Me

N H N

N Me

H N NH2 OH Me

H OR

Me -H+

IC IA L

H2N NH2

Paquette, L. A.; Han, Y. K. J. Org. Chem. 1979, 44, 4014. Wolff-Kishner reduction

A: Addition of H 2NNH2 to the carbonyl group. B: Proton transfer followed by

of N2, an extremely good leavlng group.

elimination of hydroxide ion to form a hydrazone. C: Deprotonation of the hydrazone. D: Elimination

H N O H

-H+

N OH

+ Ph +H B

ẠY

N H

OEt

EtO2C

O EtO HO

EtO2C

-OH-

KÈ

N H

A018

Ph H CO2Et

H OH

-H+ +H+ E

EtO

H Ph CO2Et

EtO2C F

Ph CO2Et

Allen, C. F. H.: Spangler, F. W. Org. Synth., Coll. Vol.

1955, 37

Knoevenagel condensation

A: Addition of piperidine to the aldehyde. B: Proton transfer followed

byelimination of hydroxide ion to form an iminium ion. C: Deprotonation of a malonate to form an enolate ( pKa RO2CCH2CO2R = 13, H2O = 15.7). D: Addition of the enelate to the iminium ion. E: Profonation of the amine and deprotonation of the malonate. F: Elimination of piperidine.

O N H

O H O

N H

O O

HO OH O

KÈ

-H

OAc

ẠY

+H+ F

O O

OAc H

OAc

H2O

N Ph

-H

+H+

OAc O C Ph

O Me

OAc H

O Me -AcOH

OAc

N H

IC IA L

A019

N H

N Ph

OH OH

Ph O Me

H O C

N H

acetone reflux

O O

N H

OH O

Ph N OAc

Herbst, R. M.; Shemin, D. Org Synth., Coll, Vol.

1943, 1

A: formation of a mixed anhydride. B: Intramolecular attack of the amide oxygen to the mixed anhydride to form an azlactone.

C: Facile deprotonation of the azlactone (aromatization).

Addition the enolate to an aldehyde followed by acetylation. E: Deprotonation followed by elimination of an enolate anion. F: Hydrolysis of the azlactone

A020

H O C

H H

Ph H

O C Ph

H OH

IC IA L

1941, 78

Kohler, E. P.; Chadwell, H. M. Org. Synth., Coll Vol.

Aldol reaction. A: Deprotonation of the ketone to form an enolate. B: Attack of the enolate to an C: Protonation and deprotonation followed by elimination of a h ydroxy ion. D: Newman

aldhyde

projection.

CO2Et H

A021

O OEt

OEt O

OEt

ẠY

KÈ

O H CO2Et

OEt

CO2Et

OEt

O CO2Et

H3O+

O CO2Et

Schaefer, J. P.; Bloomfield, J. J. Org. React. 1967, 15 14

Dieckmann condensation. A: Deprotonation of the ester to form an enolate. B: Intramolecular

addition of the enolate to the other ester, C: Elimination of ethoxide ion. D: pKa RCOCH2CO2R = 18. EtOH = 16.

A022 H O N

O N

Ac2O

O H

H O

aq HCl Me

OAc

OH Me

-2H+

+H+

O Me

H N H O

H2O

+H+ B

HO N

-H+

IC IA L

N H

KÈ

O Me

-H+

O Me

Stork, G.; Brizzolara, A.; Landesman, H.; Szmuszkovicz, J.; Terrell, R. J. Am. Chem. Soc. 1963, 85, 207.

ẠY

Stork enamine reaction. A: Addition of p yrrolidine to the ketone. B: Proton transfer followed by elimination of hydroxide ion. C: Deprotonation to form an enamine. D: Attack of the enamine to

acetic anhydride. E: Deprotonation to form a vinylogous amide. F: Protonation of the vinylogous amide. G: Addition of water to the resulting iminium ion. H: Proton transfer followed by elimination of

pyrrolidine.

A023

EtO

OEt

EtO

OEt

EtO

n-C6H13

OH OEt

+H+ E

-H+

OH -CO2

aq KOH

+H+

work up O

R O

EtO

OH OEt

EtO

O OEt n-C7H15

On-Bu

EtO

IC IA L

HO n-C7H15

Reid, E. E.; Ruhoff, J. R. Org. Synth., Coll. Vol

1943, 474.

A: Deprotonation of the malonate to form an enolate ( pKa ROH = 16, RO2CCH2CO2R = 13). B: Attack of the enolate to an alkyl bromide. C: Hydrolysis of the esters. D: Decarboxylation through a

KÈ

A024

six-membered transition state. E: Tautomerization.

OH H -H

Br Br

ẠY

A Br

Br O Br

-HBr

B Br

Br Langley, W. D. Org. Synth., Coll. Vol.

A: Acid-catalyzed formation of an enol. B: Bromination of the electron-rich enol.

1941, 127

A025 Cl P

Cl PCl2 R

OPCl2

Cl O R

Cl OH

-HCl

H2O

HO Cl

-H+

+H+

Cl Cl

Br Br

H2O

-HBr

O P

IC IA L

Formattion of an electron-rich enol followed by bromination. C: Hydrolysis of the acid chloride.

24.

A: Formation of an acid chloride. B: pKa CH3COCl = 16, CH 3CO2R =

Hell-Volhard-Zelinsky reactlon

KÈ

ẠY

O Me

A026

NaOH

O OH I

EtOH-H2O

R I

HO O Me

1941, 115

Clarke, H. T.; Taylor, E. R. Org. Synth., Coll. Vol.

-CHI3

I I

workup O

+H+

H H

HO Bergmann, E. D.; Rabinovitz, M.; Levinson, Z. H. J. Am. Chem. Soc. 1959, 81, 1239. Idioform reaction. A Elimination of an iodoform anion.

-position of the ketone. B: Addition of hydroxide ion. C:

A027 EtOH

-H+

-B Me

H O

OEt

Br HOEt

OEt Br

O Me

-AcOH

-H+

O H

H O

+H+

IC IA L

Br Br

OEt

McElvain, S. M.; Kundiger, D, Org. Synth., Coll. Vol.

C: Proton transfer followed by

A: Bromination of the electron-rich enol ester. B: Addition of EtOH.

1955, 123

A028 H BH2 A

n-Bu

B R R

U O OH

aq H2O2

NaOH

KÈ

RO B OR RO

C6H13 B C6H13 C6H13

n-Bu

BH2

elimination of AcOH. D: Addition of EtOH.

R O OH -OH B R R C

RO B R R

aq NaOH Me

OH 1988, 919

Kono, H.;Hooz, J Org. Synth., Coll, Vol,

ẠY

A: H ydroboration through a four-membered transition state. B: Attack of a h ydroperoxide anion to the

borane to form an ate complex, C: Migration of an alkyl group. D: Hydrolysis of the borate.

A029 O O O

OAc

C10H21 A OBn

O B

O R

Me2S

O R

Me S Me O

Me2S

OAc

H +

C10H21

OHC

+ H

IC IA L

OBn

Ko, K.-Y.; Eliel, E. L. J Org. Chem. 1986, 51, 5353

A: 1,3-Dipolar cycIoaddition of ozone to the olefin. B: Heterolytic cleavage of the initial ozenide. C:

D: Reductive

Recombination of the resulting 1,3-dipole and the aldehyde to form an ozonide.

cleavage of the O-O bond of the ozonide with Me 2S.

A030

H Me

Me H

O O

O OH

O Me Me O

Me Me O

Me Me -H+

Me Me

Me O

McCloskey, A. L.; Fonken, G. S.; Kluiber, R. W.; Johnson, W. S. Org. Synth., Coll. Vol

1963, 261.

ẠY

KÈ

esterication.

A: Protonation of isobutylene to form a stable tertiary carbocation. B: Attack of a carboxylic acid to the

A031

OAc Hg OAc

H2O

Me Hg OAc

OH Me Hg OAc

OH Me

NaBH4

OH Me B

Hg OAc

OH Me

Hg H

HO Me

OH Me

-Hg

OH Me D

IC IA L

Jerkunica, J. M.; Traylor, T. G. Org. Synth., Coll. Vol.

1988, 766.

A :Oxymercuration of the olefin. B: Reduction with NaBH 4 to form a Hg-H bond. C: Cleavage of the

Hg-H bond followed by extrusion of Hg to form a secondary carbon radical. D: Abstraction of a

Hydrogen atom.

A032

OTf Hg OTf

HgOTf H2O

+H+ B

OTf

-Hg(OTf )2

KÈ D

ẠY

OTf

H +H+

O HgOTf

-H+ +H+

O Me

Nishizawa, M.; Skwarczynski, M.; Imagawa, H.; Sugihara, T. Chem. Lett. 2002, 12.

A: Oxymercuration of the alkyne.

Hg(OTf)2.

-H+

HgOTf

-H+

B: Tautomerization of the enol. C: Demercuration to regenerate

A033 MeO

MeO -H+

NH2

MeO

+H+

-H2O

MeO

CF3CO2H

MeO NH

MeO

+H+

MeO NH

MeO B

MeO

IC IA L

Whaley, W. M.; Go vindachari, T. R. Org, React. 1951, 6, 151.

Pictet-Spengler reaction. A: Formation of an imine. B: Addition of an electron-rich aromatic ring to

the iminium ion followed by aromatization.

A034 MeO Me

MeO

O Cl Cl Cl P O

MeO

Me Cl Cl O Cl P O

KÈ

ẠY

MeO

MeO N

MeO

Cl Me

MeO N

MeO

-H+

Cl Me Cl O Cl P O

MeO

MeO N H

MeO

Brossi, A: Dolan, L. A.; Teitel, S. Org. Synth., Coll Vol. Bischler-Napieralski reaction. A: Attack of the o xygen atom of the amide to POCl 3.

1988 1

B: Addition of

chloride ion followed by elimination of dichlorophosphate ion. C: Deprotonation. D: Elimination of chloride ion to form a nitrilium ion. E: Attack of an electron-rich aromatic ring to the nitrilium ion.

A035

Cl Cl Cl

Cl C Cl

C B

H OH O CCl2

CHCl2

OH O

workup +H+

Cl Cl

IC IA L

Cl Cl Cl

reaction.

A: Deprotonation

of CHCl 3

-elimination

form di-

Reimer-Tiemann

Wynberg, H.; Meijer, E. W. Org. React. 1982, 28, 1.

chlorocarbene ( pKa CHCl 3 = 13.6, H2O = 15.7). B: Formation of phenoxide ion ( pKa PhOH = 10).

C: Attack of the phenoxide ion to dichlorocarbene. D: Protonation. E: Aromatization. F: Elimination of chloride ion helped by the o xygen lone pair of the phenoxide ion. G: Conjugate addition of

hydroxide ion. H: Elimination of chloride ion.

H2C CH2

A036

MeO

O O MeO

MeO

H2C

O MeO

ẠY

KÈ

MeO

Cl AlCl3 -AlCl4-

H2C CH2 Cl AlCl3 -AlCl4-

MeO

O O MeO

MeO

H2C

O O D

MeO

O MeO

Sims, J. J.; Selman, L. H.; Cadogan, M. Org. Synth, Coll. Vol.

1988, 744

IC IA L

Intramolecular Friedel-Crafts acylation. A: Formation of an acylium ion. B: Addition of ethylene to

the aeylium ion. C: Attack of the aromatic ring to the resulting primary carbocatian. D: Attack of the aromatic ring at the para position of the methoxy group to the primary carbocation. E: 1,2-Alkyl shift.

NH2

HCl

H N

+H+ C

CO2H

OH -H+

+H+

CO2H

H N

D NMe2

CO2H

H2 N

CO2H

-H+

H2O

A H

OH2

CO2H NMe2 N

H CO2H

CO2H

NMe2

A037

E OH2

CO2H

Clarke, H. T.; Kimer, W. R. Org. Synth., Coll. Vol.

1941, 3. 4,

A: Formation of nitrous anhydride. B: Addition of the aniline to nitrous anhydride. C: Proton transfers fallowed by elimination of water to form a diazonium salt. D: Addition of electron-rich dimethylaniline

KÈ

to the diazonium salt. E: Aromatization.

A038

ẠY

Na/NH3

H OEt Me

A Me

H H Me

Me > C

IC IA L

H OEt

Paquette, L. A.; Barrett, J. H. Org. Synth., Coll. Vol.

1973, 467.

Birch reduction. A: Single electron transfer (SET) from Na to the aromatic ring to form a radical anion.

B: Protonation. C: More substituted olefins are formed because alkyl groups destabilize a carbanion.

OMe O

A039 OMe O H

OMe O

NH2

H NH2

U Q C7H15Br

ẠY

CO2H C7H15

H2O

CO2H C7H15

O CO2H C7H15

-H+

O O C7H15

H CO2 C7H15

OMe

C6H13 Br

OMe

H H

OMe CO2

KÈ

O B

OMe

CO2

OMe

OMe O

-H+ +H+ F

H HO O Me CO2H C7H15

H -H+ +H+ I

O C7H15

H3O+

C7H15

Taber, D. F.; Gunn, B. P.; Chiu, I.-C. Org. Synth., Coll Vol Birch reduction

1983, 249.

A: Single electron transfer (SET) to form a radical stabilized by the carboxylate. B:

Protonation of the radical anion, C: SET to form a dianion species. D: Alkylation of the dianionic species. E: Protonation of the electron-rich enol ether. F: Addition of water followed by proton transfer. G: Elimination of MeOH. H: Decarboxylation through a six-membered transition state.

IC IA L

I: Tautomerization.

A040 Na H

O O

OMe

MeO

O N

OMe

F MeO2C

O N

O B

O MeO2C

O N

CO2Me

Selvakumar, N.; Reddy, B. Y.; Azhagan, A. M.; Khera, M. K.; Babu, J. M.; Iqbal, J

Tetrahedron Lett. 2003, 44, 7065

A: Deprotonation of the malonate to form an enolate ( pKa RO2CCH2CO2R = 13, H2 = 35), B:

Nucleophilic addition of the enolate to the electron-deficient aromatic ring. C: Elimination of fluoride

ẠY

KÈ

ion.

A041

Br Me

H O

P Br

Me A

Me Br

H O

Me P Br

Br B

Noller, C. R.; Dinsmore, R. Org. Synth., Coll. Vol. A: Attack of the alcohol to PBr3.

B: SN2 reaction.

1943, 358

A042

O OH

OH Cr OH O

OH r C OH O

-H2O

+H+

H2O

O OH

O C

IC IA L

Cr O

1973, 310.

B:Attack of the alcohol to H2CrO4. C: Elimination of H2CrO3.

Jones oxidation. A: Hydration of CrO3.

Eisenbraun, E. J. Org. Synth., Coll. Vol

A043

N Y

O S

O Me

-CO2 -CO

Cl Cl S Me Me

Cl O S

KÈ

Cl Cl S Me Me R

ẠY

O H

H R

CH3 S Me O

Me Me S O Cl

-HCl R

-Me2S D

NEt3

LeopoLd, E. J. Org. Synth., Coll. Vol.

1990, 258.

Swern Oxidation. A: Attack of D MSO to (COCl)2 to form a chlorosulfonium ion with generation of CO and CO2.

B: Attack of an alcohol to the chlorosulfonium ion. C: Formation of a sulfur ylide. D:

-Elimination of Me 2S.

A044

H O

H O O O I O O R

HO R

O O HO I O HO O

-H+ +H+

Me Me Me Me

O O I O O

O A

B R

O H

-H2O

IC IA L

O O I O O

Me Me

Schmid, C. R.; Bryant, J. D. Org. Synth., Coll. Vol

1995, 450

A: Formation of a cyclic intermediate. B: Cleavage of the C-C bond to form two molecules of the

aldehyde,

A045 CO2Et N N

EtO2C

CO2Et O N N H Ph3P O

EtO2C

Ph3P

EtO2C CO2Et N NH Me Ph3P

ẠY

KÈ

O H

Ph3P

EtO2C CO2Et N NH Me

CO2Et

Ph3P

O Me O

O H

EtO2C CO2Et - HN NH

CO2Et

O - Ph3P O

CO2Et

Mitsunobu, O. Synthesis 1981 1 Mitsunobu reaction. A: Conjugate addition of Ph 3P to DEAD to form a zwitter ion. B: Deprotonation to the most acidic proton in the reaction system. C: Attack of the alcohol to the activated reagent followed by deprotonation. D: Attack of the carboxylate with inversion of configuration.

A046 Br

O H

Me Me

Me H Me O H

IC IA L

Me Me

Zhong, G.-F.; Schlosser, M. Synlett. 1994, 173

Wanger-Meerwein rearrangement. A: Protonation of the alcohol. B: Elimination of water assisted by

cleavage of the C-C bond to form a stable tertiary carbocation C: Deprotonation to form an olefin.

-H2O

A047

-H+

Walter, C. R., Jr. J. Am. Chem. Soc. 1952, 74, 5185.

pinacol rearangement. A: Protonation of the alcohol followed by elimination of water to form a tertiary

KÈ

center. B: 1,2-Alkyl shift helped by the oxygen lone pair of the hydroxy group.

ẠY

A048

Me A

Me B

O H

Me +

-H D

C Me

H OH

Me OH

Waring, A J.; Zaidi, J. H.; Pilkington, J. W. J. Chem. Soc., Perkin Trans.

1981, 1454.

Dienone-phenol rearrangement. A: Protonation of the ketone. B: 1,2-Alkyl shift to form a stable tertiary carbocation. C: 1,2-Alkyl shift to form a stable tertiary carbocation. D: Aromatization by

A049 Me

Me Me

A OH

Me Me

C Ph

-H+

Me Me

O N

N C Ph

OH N

Me Me

OH2

Me Me

IC IA L

deprotonation.

Tillmanns, E.-J.; Ritter, J. J. J. Org. Chem. 1957, 22, 839

Ritter reaction. A: Protonation of the tertiary alcohol followed by elimination of water to form a more stable tertiary carbocation.

B: Attack of PhCN to the carbocation to form a nitrilium ion.

Intramolecular addition of the hydroxy group to the nitrilium ion.

A050 Me

N N

KÈ

ẠY

-N2 A

Me H SnBu3

NC Me

B Bu3Sn

Bu3Sn H Hamon, D. P. G.; Richards, K. R. Aust. J. Chem. 1953, 36, 2243 A: Thermal decomposition of AIBN to gi ve the stable tertiary radicals. B: Abstraction of a hydrogen atom from Bu 3SnH. C: The resulting tin radical reacts with a halide to form a carbon radical. D: Abstraction of a hydrogen atom from Bu 3SnH to continue the radical chain reaction.

A051

S I CH3

Bu3Sn

S O

H Ph

Bu3SnH

MeS

N O

H Ph

N O

E N O

H Ph

Bu3Sn H

Bu3Sn

AIBN C

MeS

H Ph

MeS

H Ph

IC IA L

S C S

N O

Comins, D, L.; Abdullah, A. H. Tetrahedron Lett. 1985, 26, 43.

Barton-McCombie deoxygenation. A: Deprotonation of an alcohol. B: Addition of the alkoxide ion to

CS2 followed by methylation to form a xanthate. C: Generation of a tin radical. D: Attack of the radical to the sulfur atom of the xanthate to form a stable carbon radical. E: Cleavage of the C-O bond

to form a secondary carbon radical. F: Abstraction of a hydrogen from Bu 3SnH.

KÈ

A052

ẠY

N H

B Cl

O O H2N NH2

H2NNH2 N Ph O

O O +

-H

+H+ C

NH NH2 NH Ph

-H+ +H+ D

O NH NH NH2

NH NH

H2N

Ph Manske, R. H. F. Org. Synth., Coll. Vol.

1943, 83.

IC IA L

Gabriel synthesis. A: pKa RCONHCOR = 9.6,

HCO3-

= 10.3. B: Afkylation, C: Addition of H 2NNH2

to the imide to form a hydrazide. D: Intramolecular addition of the amino group of the hydrazide to the

amide carbonyl to release benzylamine.

A053

OH2

-H+

NH2

N Me

aq H2O2

-CO2 B

N Me D

O NMe2

O NMe2 E

OH H O NMe2

HO OH

HN Me

HN CH2

+H+ A

-H2O

KÈ

Cope, A, C.; Bumgardner, C. L.; Schweizer. E. E. J. Am. Chem. Soc. 1957, 79, 4729

Eschweiler-Clarke methylation (A-C)and Cope elimination (E). A: Addition of the amine to formaldehyde followed by dehydration to form an immium ion. B: Hydride transfer from a formate and

ẠY

to the iminium ion with generation of CO2.

C: Iteration of the same steps. D: Oxidation of the tertral

amine to form an N-oxide. E: syn-Elimination.

A054

O O -H+

O OH

O H O

O O

IC IA L

Krow, G. R. Org. React. 1993, 43, 251.

Baeyer-Villiger oxidation. A: Acti vation of the carbonyl group by protonation. B: Addition of mCPBA

to the carbonyl group. C: 1,2-Alkyl shift helped by the o xygen tone-pair with cleavage of the peroxide

to form a lactone.

OH2

A055

N B O

-H+

KÈ

-H+

H2O

+H+

Eck, J. C.; Marvel, C. S. Org. Synth., Coll. Vol.

1943, 76.

Beckmann rearrangement. A: Protonation of the oxime. B: Migration of the alkyl substituent with

ẠY

simultaneous cleavage of the N-O bond.

A056

O H

A O H

B O

O OH

H O OH O

O H

O D O

workup

+H+

Dakin. H. D. Org. Synth., Coll. Vol.

1941, 149.

IC IA L

Dakin reaction. A: Deprotonation of the phenol ( pKa PhOH = 10, H2O = 15.7). B: Addition of

hydroperoxide ion to the carbonyl group. C: Attack of the electron-rich aromatic ring to the peroxide oxygen with cleavage of the O-O bond to form an epoxide. D: Cleavage of the epoxide to restore the

aromaticity, E: Hydrolysis of the resulting formate.

A057 O

MeO

O H

Cl OH

HO H Ar

O OH

H OH -CO2 O

H N

MeO

NH2

N H

N Cl

H N

O C N

O C

N H

Cl OH

MeO

Buck. J. S.; Ide, W. S. Org. Synth., Coll. Vol.

1943, 44

Hofmann rearrangement. A: pKa RCONH 2 = 17, H2O = 15.7. B: Chlorination of the amide anion.

KÈ

C: Deprotonation. D: The anion on the nitrogen atom induces migration of the aromatic ring with cleavage of the N-Cl bond to form an isocyanate.

E: Addition of hydroxide ion to the isocyanate. F:

ẠY

Decarboxylation.

A058

O Ph

O O H

NEt3

Ph A

O OEt

O O

OEt Cl

N O N Ph

OEt

O O

OEt

O Ph

N N N

-N2

N N N

IC IA L

N N N

1988, 910.

Kaiser, C.; Weinstock, J. Org. Synth., Coll. Vol

Curtius rearrangement. A: Formation of a mixed anhydride. B: Addition of azide ion to the mixed anhydride occurs at the more electron-deficient carbonyl group to form an acyl a zide. C: Migration of

the carbon atom to the nitrogen proceeds with retention of configuration as N 2, an extremely good

leaving group, departs from the molecule.

Me O H

N N

Me O

A H

-H+ H H

-H+

O C H2O

CO2H

KÈ

+H C

-N2

A059

Wheeler, T. N.; Meinwald, J. Org. Synth., Coll. Vol

1988, 840.

Wolff rearrangement. A: Photo-induced generation of a carbene. B: Insertion of the carbene to the

ẠY

C-C bond results in a ring contraction to form a ketene. C: Addition of water to the ketene.

A060

O MeO

O Cl

OMe B

O OMe

OMe H

OMe D

Goheen, D. W.; Vaughan, W. R. Org. Synth., Coll. Vol

1963, 594.

Favorskii rearrangement. A: Deprotonation to form an enolate. B: Formation of a cyclopropanone.

IC IA L

C: Addition of methoxide ion to the carbonyl group. D: Cleavage of the cyclopropane ring with simultaneous protonation.

MeLi Me

Br Br

Ot-Bu

Br Br Br

A061

Skattebel, L,; Solomon, S. Org. Synth., Coll. Vol. A: Generation of a dibromocarben

-elimination of HBr,

1973, 306,

B: Insertion of the carbene to the olefin

toform a cyclopropane. C: Halogen-lithium exchange. D: Generation of a carbene. E: Insertion of

the carbene to the C-C bond to form an allene.

A062 H

O OMe

OMe A

ẠY

KÈ

OMe

O OMe A

OH - + OMe H +H+ B

Allen, C. F. H; Gates, J. W., Jr, Org. Synth., Coll. Vol. A: Allylation of the phenol. Aromatization.

OMe

1955, 418

B: [3,3] Sigmatropic rearrangement (Claisen rearrangement).

A063 H O

+H+

H O B

IC IA L

H -H+ O

1973.25

Howard, W. L.; Lorette, N. B. Org, Synth., CoIl Vol.

A: Protonation of an oxygen atom of the acetal. B: Elimination of allyl alcohol helped by the oxygen lone pair of the acetal. C: Deprotonation to form an enol ether. D: [3,3] Sigmatroplc rearrangement

(Claisen rearrangement).

A064 O

CO2Me

A CO2Me

B CO2Me

CO2Me

Ziegler, T,; Layh, M.; Effenberger, F. Chem. Ber. 1987, 120, 1347.

A: Diels-Alder reaction. B: Retro Diels-Alder reaction.

A065

KÈ

ẠY

NH OH

N O

N H OH

Ph Ph H

N O

-H+ +H+ B

N OH

Ph Ph

N O

-H2O

Ph C

Ph N O Ph

Brüning, I.; Grashey, R.; Hauck, H.; Huisgen, R.; Seidl, H, Org. Synth., Coll. Vol.

1973, 1124

A: Addition of a hydro xylamine to the aldehyde. B: Proton transfer followed by elimination of water to form a nitrone cycloaddition).

C: 1,3-Dipolar cycloaddition of the nitrone to stvrene (electronically, [4+2]

A066 Cl O H

O H

-HCl

or Cl

Cl OH

-HCl E

O H

IC IA L

Schiess, P.; Barve, P. V.; Dussy, F E.; Pfiffner, A. Org. Synth., Coll. Vol. A: Isoerization to form an o-quinodimethane.

B: Elimination of HCl to form a ketene.

N O

O H

A067

KÈ

A068

ẠY D

Rondestvedt, C. S., Jr. Org. Synth., Coll. Vol. /V 1963, 766

Ene reaction.

OH H Se O OH

C: 4e

Elimination of hydrogen chloride to form a ketone.

1998, 28.

H2O + O Se O

HCl OAc

HO Se O HO

-H2O

A HO

Se OH OH

R O

O Se

Me OAc

Se OH

O Ot-Bu H

H O Se

IC IA L

-Se O

O H

O Se O Ot-Bu

Umbreit, M. A.; Sharpless, K. B. J. Am. Chem. Soc. 1977, 99, 5526. B: [2,3] Sigmatropic rearrangement.

A: Ene reaction occurs on the least hindered olefin.

Elimination of the alcohol. D: Oxidation of SeO with TBHP to regenerate SeO2.

PPh3 CH2

O PPh3

O PPh3 - Ph P O 3

A069

CH2

Wittig, G.; Schoellkopf, U. Org. Synth., Coll. Vol

1973, 751.

Wittig reaction. A: Addition of the ylide to the carbonyl group to form a betaine. B: Attack of the

alkoxide to the phosphonium cation to form an oxaphosphetane. C: Irreversible elimination of Ph 3PO.

A070 O

Br Me

KÈ

OEt

O (EtO)2P

-EtBr OEt

O (EtO)2P

O OEt

P(OEt)3

van der Klei, A.; de Jong, R. L. P.; Lugtenburg, J.; Tielens, A. G. M. Eur. J. Org. Chem. 2002, 3015.

ẠY

Arbuzo v reaction. A: Attack of P(OEt) 3 to the reacti ve bromoacetate to release bromide ion (SN2 reaction). B: Attack of the resulting bromide ion to the ethyl group in an SN2 fashion to form a

phosphonate.

A071 O (EtO)2P

O (EtO)2P

OEt H

A H Na

O O P(OEt2)

OEt O Na

OEt C

B O

OEt O

Wadsworth, W. S., Jr.; Emmons, W. D. Org. Synth., Coll. Vol.

1973, 547.

Horner-Wadsworth-Emmons reaction. A: Deprotonation of the phosphonate. B: Addition of the phosphonate ion to the ketone. C: Attack of the alkoxide to the phosphonate followed by elimination of a phosphate ion to form an olefin.

IC IA L

A072 OH2 H

H2N H2N

H2N

NH CN

H2N

H OH N S

workup

H2N

S OH

NaOH

CN H

NH2

H2N

Gerber, R, E.; Hasbun, C.; Dubenko, L. G.; King, M. F.; Bierer, D. E. Org. Synth., Coll. Vol.

2002, 475

A: Attack of the more reactive sulfur atom of thiourea to the alkyl chloride to form an isothiourea (SN2

reaction). B: Hydrolysis of the isothiourea.

A073 O

KÈ

ẠY D

HO OH

O Me SePh

aq H2O2

PhSe Cl

O Me SePh

O Me

Na H

O Me SePh O H

Me SePh O

O D

HO Renga, J. M: Reich, H. J. Org. Synth., Coll. Vol.

-diketone ( pKa RCOCH 2COR = 9, H2 = 35). B

C: Oxidation of the selenide to form a selenoxide. D

-Elimination.

1988.23 -position.

A074 BrMgO

O MgBr

SiMe3

OH SiMe3

workup +H+

H2C SiMe3

NaH

H SiMe3

SiMe3

IC IA L

-Me3SiO-

Ager, D. J. Org. React. 1990, 38, 1.

Peterson olefination. A: Addition of Me3SiCH2MgBr to the ketone. B: Exchange of the counter cation from Mg to Na. C: Elimination of a silanol ion via a four-membered transition state.

CO2Me

Me Br

Me CO2Me

Pd(0)Ln

ẠY

KÈ

PdLn

-Elimination. C: Reductive

N Me Br

Pd(0)Ln

Reduction of Pd(OAc) 2 to Pd(0) using Et3N. A: Ligand exchange. B elimination of AcOH.

-AcOH

AcO Pd H

Et3N

NEt2

Me H AcO Pd NEt2

AcO Pd OAc

A075

PdLn Br

Me Me

F CO2Me

G HBr

Br H PdLn Me

Patel, B. A.; Ziegler, C. B.; Cortese, N. A.; Plevyak, J. E.; Zebovitz, T. C. Terpko, M.; Heck, R. F. J. Org. Chem. 1977, 42, 3903. Heck reaction. D: Oxidative addition. E: Carbopalladation. F

-Elimination to form the product. G:

Reductive elimination of HBr.

Pd(OAc)2 + 2Ph3P

AcO

OAc

AcO

Pd Ph3P

IC IA L

A076 OAc

AcO

Pd PPh3

Ph3P

PPh3

Ph3P

Reduction of Pd(OAc)2 to Pd(0) using Ph 3P.

(HO)3B

(HO)2B

Activation of boronic acid,

OHC

O PPh3 Ph3P Pd(0) + Ac2O

Ph3P

O O Pd PPh3

AcO

PPh3

Me OAc AcO Pd PPh3 Ph3P

OAc

ẠY

KÈ

Pd(0)Ln

OHC

C OHC

Br PdLn

(HO)3B

PdLn

BrB(OH)3 Huff, B. E.; Koenig, T. M.; Mitchell, D.; Staszak, M. A. Org. Synth., CoIl Vol.

2002, 122

Suzuki-Mi yaura coupling. A: Oxidative addition. B: Transmetallation. C: Reductive elimination.

A077 O

2HCl + 1/2O2 H2O

PdCl2

2CuCl2 D

IC IA L

2CuCl

Pd(0)

Cl H

Pd Cl

Tsuji, J.; Shimizu, I.; Yamamoto, K. Tetrahedron Lett. 1976, 34, 2975.

Wacker oxidation, A: Olefin complexation. B: Oxypalladation. C: Hydride shift. D: Oxidation of Pd(0) with CuCl 2 to regenerate PdCl 2.

E: Oxidation of CuCl with O2 to regenerate CuCl 2.

A078

Boc N

ẠY

KÈ

LnRu

RuLn

Boc N

- H C RuLn 2

R B

Boc N RuLn

Boc N

C RuLn

Ferguson, M. L.; O'Leary, D. J.; Grubbs, R. H. Org. Synth. 2002, 80, 85. Ring closing metathesis (RCM). A: C ycloaddition of a ruthenium carbene complex to the olefin to from a metallacyclobutane.

B: Retro cycloaddition.

C: Intramolecular cycloaddition of the ruthenium

carbene complex. D: Retro cycloaddition to regenerate a ruthenium carbene complex.

ẠY M

KÈ Y

Q H

N Ơ N

IC IA L

B001 OH -H+

NHMe

NH2 +H+ Me

-H+ +H+ A

CHO

OH2

+H+ N Me

N Me

IC IA L

HO2C OH CO2H +

-H

MeN

+H+ B

N Me

O CO2H +H+

MeN

OH C CO2H

O H O

MeN

OH CO2H

H MeN

MeN

-CO2

+H+

O H CO2H

CO2H

-H+

O H -CO 2 O D

-H+

MeN

-H+

-H2O

CO2H

H2O

-H2O

CO2H

HO2C

-H+

MeN

+H+

Cope, A. C: Dryden, H. L.: Howell, C. F Org. Synth., Coll. Vol. A: Formation of a cyclic hemiaminal.

B: Mannich

reaction

Robinson-Schöpf reaction.

1963, 816

KÈ

Intramolecular Mannich reaction. D: Decarboxylation through the six-membered transition state.

i-PrO Oi-Pr Al O O Ph Me H Me

Al(Oi-Pr)3

O A

ẠY

B002

Al(Oi-Pr)2 H

O Me

Me B

OH aq HCl

Wilds, A. L. Org. React. 1944, 2. Meerwein-Ponndorf-Verley reduction. A: Formation of an ate complex. B: H ydride transfer via a six

membered transition state with formation of acetone.

B003 H

NH2NH2

+H+

-H+

-H2O

H2N

N H

O H

H -N2 B

+H+

H2N

H2O NHNH2

-H+

H HO NHNH2

IC IA L

Wharton rearrangement.

Wharton, P. S.: Bohlen, D. H. J. Org. Chem. 1961, 26, 3615. A: Cleavage of the epoxide helped by the nitrogen lone pair of the

hydrazone. B: Elimination of N 2 (an extremely good leaving group).

KÈ

HOO

B004

ẠY

-OHO

A O

ArSO2NHNH2

aq K2CO3

-H2O

N NH SO2Ar

-N2 -ArSO2-

E N N O

S Ar O

O O

B H N N SO2Ar

Reese, C. B.; Sanders, H. P. Synthesis 1981, 276. Eschenmoser fragmentation. A: Michael addition. B: Formation of an epoxide (the O-O bond is activated). C: Formation of a hydrazone. D: pKa HCO3- = 10.3, ArSO 2NH2 = 8.5. E: Fragmentation involving a loss of N2 and a sulfinate ion.

H CN

IC IA L

B005

CN A N

O CN

-CNCN

C N

N 1988, 866

Stetter, H.; Kuhlmann, H.; Lorenz, G. Org. Synth., Coll Vol.

A: Formation of the less favored cyanohydrin carbanion. B: Michael addition. C: Regeneration of the

cyanide ion (cyanohydrin is unstable under basic conditions).

Bn H

M KÈ

ẠY

Me Bn

O H

Me Me Bn

O Bn

N S

NEt3

Me HO

B006

N O

+ Me

Me O

Me Stetter, H.; Kuhlmann, H.; Haese, W. Org. Synth., Coll. Vol Stetter reaction. A: pKa thiazolinium ion = 10, (

HNEt3+

1993. 52

= 10.7. B: Generation of a stabilized carbanion

ref B005). C: Michael addition. D: Regeneration of the thiazolinium ion.

B007

O Me

OAc

H2O

-AcOH

aq HCl

AcO

O Me

O O Me

OAc O

O O

IC IA L

1955, 425.

Rajagopalan, S.; Raman, P. V. A. Org. Synth., Coll. Vol.

Perkin reaction. A: pKa (CH 3CO)2O = 13.5, AcOH = 4.8 (a small amount of the acetic anhydride anion can be formed).

B: Intramolecular acyl transfer.

C: Formation of a mixed anhydride.

Base-catalyzed elimination of acetic acid.

B008

KÈ ẠY

O Me

Me O

B Me

O Me

N H benzene reflux

O Me

MeO H

-H+ N H

+H+

O Me HO N

O Me C

O Me

HCl

O Me

HO N

+H+

-H+

O Me

H2O

O Me

-H+

aq HCl

O Me

IC IA L

1973, 486

Ramachandran, S.; Newman, M. S. Org. Synth., Coll. Vol.

Robinson annulation. A: pKa RCOCH 2COR = 9, H2 O = 15.7. B: Michael addition. C: Formation of

KÈ

B009

an enamine followed by an intramolecular addition to the ketone.

MeO2C

OMe A

ẠY

MeO2C

OMe

Ph Ph H

OMe OMe

O OMe O

OMe

Ph H

OMe

O O

Ph OMe O O

H CO2Me

O OMe O

Ph C

workup +H+

OMe

CO2H

OMe Johnson, W. S.; Daub, G. H. Org. React. 1951. 6

IC IA L

Stobbe condensation. A: pKa CH3CO2R = 24, MeOH = 15.5. B: Formation of a five-membered lactone. C: Elimination of the carboxylate occurs by avoiding the steric repulsion between the phenyl

B010 Me

O OMe

H3C N N

-N2

H2C N N

and the methoxycarbonyl groups.

Black, T. H. Aldrichimica Acta 1983, 16, 3

A: pKa CH3CO2H = 4.8, CH 3N2 = 10.2. B: The SN2 reaction occurs in a solvent cage.

B011

KÈ

OTs

ẠY D

Li/NH3

OTs

workup O

+H+

O H

Stork, G.; Tsuji, J. J. Am. Chem. Soc. 1961, 83, 2783. Two successive SET reactions followed by cyclopropane formation.

B012 CN Cl

CN A

CN B

Cl NH2

IC IA L

NH2

H NH2

Skorcz, J. A.; Kaminski, F. E. Org. Synth., Coll. Vol.

1973.263

A: pKa CH 3CN = 25, NH3 = 35. B: Formation of benzyne followed by an intramolecular nucleophilic

addition.

B013

NH2

N N

CuCl

NaNO2 HCl

CuCl2 B -CuCl D

Cl CuCl

Ropp, G. A.; Coyner, E. C. Org. Synth. Coll, Vol

1963. 27

Meerwein arylation. A: Formation of a diazonium salt ( ref A037). B: SET induces a loss of N 2 to form

KÈ

a phenyl radical. C: Addition of the phenyl radical to butadiene to form a stabilized radical. D:

ẠY

Recycle of CuCl to continue the radical chain reaction.

B014

Cy N C N Cy A

H O N C N Cy S Cy Me Me

CyHN CyN

Me O S Me Me H

Me Me

CyHN

-H+

O +

+H B

CyHN

S Me

-Me2S

Me H

Me Me

O H

IC IA L

or Me Me

S CH2 H

-Me2S

Tidwell, T. T. Org. React. 1990, 39, 297. Pfitzner-Moffatt o xidation. A: Activation of DCC by protonation. B: Nucleophilic substitution at the -Elimination of dimethyl sulfide might proceed either by 1) direct deprotonation with a

sulfur atom. C

base or 2) formation and collapse of a sulfur ylide.

B015 H2O

H HO

-H2O Br

Ferreri, C.; Ambrosone, M. Syn. Commun. 1995, 25, 3351.

KÈ

A: Generation of a carbocation stabilized by a cyclopropyl group. B: Cleavage of the cyclopropane ring occurs by avoiding the steric repulsion to form the trans -product.

ẠY

B016

OTs

OTs H O

Ot-Bu Wharton, P. S.; Hiegel, G. A. J. Org. Chem. 1965, 30, 3254. Grob fragmentation. This Grob fragmentation can occur when the orbitals of the breaking C-C o-bond and C-

-bond overlap on the same plane (antiperiplanar interaction).

B017 Me Me Me n-Bu3Sn

Me Me

IC IA L

AIBN

n-Bu3SnH

C H

n-Bu3Sn H H Me Me Me H

H Me

Me Me

-n-Bu3Sn

Weinges, K.; Reichert, H.; Huber-Patz, U.; Irngartinger, H. Lieb igs Ann. Chem. 1993, 403. A: Generation of a tin radical ( ref A050). B: Attack on the iodide to initiate the radical chain reaction. 5-exo-dig Radical cyclization.

C: 5-exo-trig Radical cyclization. D:

B018 O

H CCl3

KÈ

O O

CCl3

CCl3 -CCl3

C Cl3C H Dowbenko, R. Org. Synth., Coll Vol.

1973, 93.

A: Homolytic cleavage of dibenzoyl peroxide. B: Generation of a trichloromethyl radical which then

ẠY

adds to 1,5-cyclooctadiene. C: Transannular radical cyclization.

B019

Ph N Cl

A Me

O O

-PhCH2Cl B

O O

-Cl-

MeOH N O

N H

OMe

+H+

HOMe

-CO2

NH HCl

IC IA L

reflux

-H+

Yang, B. V.; O'Rourke, D.; Li, J. Synlett. 1993, 195.

A: Acylation of a tertiary amine. B: Attack of chloride ion on the benzylic position. C: E1 elimination

ofthe chloride followed by addition of methanol, D: Elimination of the carbamic acid helped by the oxygen lone pair of the methoxy group. E: Decarboxylation.

B020

Me CO2Me

C5H11

-MeI

CO2Me

C5H11

Me Me Si O O

Me I Si Me Me O

-Me3SiOMe CO2Me

C5H11

Me Me Si O O e MeOH M OH N C5H11 CO2Me C Me

Me Me Si O O

KÈ

CO2Me

ẠY

C5H11

-CO2

H N

C5H11

CO2Me

Laurent, P.; Braekman, J.-C.; Daloze, D. Eur. J. Org. Chem. 2000, 2057.

A: Sil ylation of the electron-rich oxygen of the carbamate. B: Demethylation by SN2 reaction. C: Methanolysis of the silyl carbamate.

B021 O

EtO2C N

PdLn O

EtO2C N

PdLn

NHEt2

EtO2C N

O Pd Ln

-PdLn -CO2

EtO2C N

Et N Et

LnPd

EtO2C +

NEt2

IC IA L

Genet, J. P.; Blart, E.; Savignac, M.; Lemeune, S.; Lemaire-Audoire, S.; Bernard, J. M. Synlett 1993, 680.

-allylpalladium complex. B: Attack of Et2

-allylcomplex.

B022 Ph

O O O O N S N S Ph

- PhS

O O O O N S N

O2N

MeO

PhS H

PhS

MeO

O S

H SPh

KÈ

MeO

O S

O H

-SO2

MeO

ẠY

Kurosawa, W.; Kan, T.; Fukuyama, T. Org. Synth., Coll. Vol.

2004, 482.

A: Addition of a thiolate ion to the electron deficient aromatic ring to form a Meisenheimer complex. B:

Elimination of an amidosulfurous acid anion which, upon protonation and extrusion of SO2 , gi ves an amine.

B023 O

O BF3-Et2O

Me Me

O Me

Me Me

O BF3 Me

BF3 O

O A

O B

Me Me

CHO Me

Me Me

Ryerson, G. D.; Wasson, R. L.; House, H. O. Org. Synth., CoIl Vol

1963, 957.

IC IA L

A: Cleavage of the epoxide to form the more stable tertiary carbecation (formation of a carbocation next

to a carbonyl group is unusually difficult). B: Wagner-Meerwein-type rearrangement.

B024

H2C N N

Me N N OH

O Me S N A O N O H OH OH

OH H H2C N N

O H2C N N

-N2

N N

de Boer, T. J.; Backer, H. J. Org. Synth., Coll Vol

1963, 225.

A: H ydrolysis of N-methyl-N-nitrososulfonamide. B: Formation of diazomethane. pKa CH3N2 = 10.2,

H 2O = 15.7. C: Addition of diazomethane to a ketone followed by ring expansion (cf. Tiffeneau-

KÈ

Demjanov rearrangement).

B025

ẠY

Me CN

Me Me

NC H CN

Kametani, T.; Kondoh, H.; Tsubuki, M.; Honda, T. J. Chem. Soc., Perkin Trans.

Me M H e 1990, 5.

A: 4e Conrotatory electrocyclic reaction to form an o-quinodimethane. B: Intramolecular Diels-Alder

reaction.

B026 FeCl3 O

FeCl3

A SiMe3

SiMe3

O FeCl3

O FeCl3 B

SiMe3

workup

SiMe3

O FeCl3

IC IA L

SiMe3

Jones, T. K.; Denmark, S. E. Helv. Chim. Acta 1983, 66, 2397.

Silicon-directed Nazarov reaction. A: Acti vation of the carbonyl group with FeCl 3, a Lewis acid. B: 4e

Conrotatory electrocyclic reaction. C: Desilylation to form the olefin regioselectively.

B034

hv 1O 2

KÈ

3O 2

O O

ẠY D

O O

1O 2

Et3N

O O

OH +H+

H Et3N

C O

O Balci, M. Chem. Rev. 1981, 81, 91.

A: Generation of singlet oxygen. endoperoxide.

B: Diels-Alder reaction.

C: Base-induced cleavage of the

B035 hv

O O

1O 2

O O

1O 2

O O

Ph3P

- Ph3P O

C PPh3

IC IA L

3O 2

Balci, M. Chem. Rev. 1981, 81, 91

A: Generation of singlet oxygen. B: Diels-Alder reaction. C: Reductive cleavage of the endoperoxide D: Formation of an epoxide via SN2' reaction with elimination of

with triphenylphosphine.

triphenylphosphine oxide.

CrCl2

KÈ ẠY D

H OCrCl2

Me H

O CrCl2

CrCl2

B041

Ph Me

O CrCl2 OH

workup +H+

Ph Me

Okude, Y.; Hirano, S.; Hi yama, T.; Nozaki, H. J. Am. Chem. Soc. 1977, 99, 3179.

A: Since CrCl2 is a single electron reductant, two molecules of CrCl 2 are needed to convert an alkyl bromide to the corresponding organochromium species. B: Addition to an aldehyde via a chair-like six-membered transition state.

B042 O n-Bu HRh(CO)L2

E O H L2 Rh H CO

H L2 Rh CO

n-Bu B

IC IA L

n-Bu

L2 Rh CO O

CO L2 Rh CO

n-Bu L2 Rh CO

n-Bu

Hallman, P. S.; McGarvey, B. R.; Wilkinson, G. J. Chem. Soc. (A) 1968, 3143.

Hydroformylation. A: Complexation of the catalyst with an olefin. B: Hydrometallation. C: Insertion

B045

N C

H Ph

S B

H Ph

SCN

N C O

KÈ

Ph S C

O C N

S Ph H

Guss, C. O.; Chamberlain, D. L., Jr. J. Am. Chem. Soc. 1952, 74, 1342.

ẠY

A: Cleavage of the epoxide by SN2 reaction at the less hindered position. B: Migration of the cyano

group. C: Intramolecular SN2 reaction with inversion of configuration.

B046 O

-H+ Me

MeO

HO NMe2

OMe

HN Me

MeO

OMe

Me HO

H MeO

Me Me

OMe

Me -MeO-

-H+ Me

Me Me

B OMe

-MeO

MeO

Me Me

HO NHMe2

OH2 - + H

-MeO

-H

Me2N

NMe2

MeO

Me HN Me

IC IA L

MeO

Kozmin, S. A.' He, S.; Rawal, V. H. Org. Synth., Coll. Vol.

2004, 301.

A: Formation of an enamine to eliminate methoxide ion. B: Conjugate addition of dimethylamine to the

-unsaturated iminium ion.

-MeO-

OMe

H N

-H+

OMe

+H+

H OMe

MeO

H Me N

B047

OBn

OBn H

N O

OBn H

ẠY

KÈ

N O

OMe NO2

OBn N

Raney Ni NH2NH2

MeO H OBn N

D NO2

NH2

NO2

OBn H -

-MeO

-MeO-

-H+

OBn

OMe

OBn

OBn +

-H

+H+

F NH2

N H H

N H

H N

OBn

N H

OBn H

-H

G N H

N H Batcho, A. D.; Leimgruber, W. Org. Synth., Coll. Vol

1990

IC IA L

Leimgruber-Batcho indole synthesis. A: Generation of an iminium ion under thermal conditions. B:

Replacement of dimethylamine with pyrrolidine. C: Generation of a benzylic carbanion stabilized by o-nitro group. D: Formation of an enamine. E: Reduction of the nitro group. F: Protonation of the

enamine to form the reactive iminium ion. G: Elimination of pyrrolidine helped by the nitrogen lone

pair.

B048 ArO2S

ArO2S

H A

Q OEt

SO2Ar H OEt

N Ar

SO2Ar C

S O O

-ArSO2-

Oldenziel, O. H.; Wildeman, J; van Leusen, A. M. Org. Synth., Coll. Vol

ẠY

OEt

KÈ O

SO2Ar

OEt

N H SO2Ar

H OEt O

SO2Ar

t-BuO K

C N

1988, 41.

TosMIC (p-toluenesulfonylmethyl isocyanide). A: Deprotonation of an active methylene compound.

B: Intramolecular addition to the isocyanide to form an oxazoline anion. C: Loss of the activated formyl

group with a concomitant elimination of a toluenesulfinate ion ( pKa PhSO2H = 1.5).

B049 Ph3P Br

O Br Br

Br Br C Br

O Br Br

n-C7H15

Br Li

PPh3 B

FF n-C7H15

n-C7H15

workup

n-C7H15

+H+

n-Bu

n-C7H15

-LiBr

n-C7H15

H n-C7H15

n-C7H15

Ph3P

n-Bu

BuLi

n-C7H15

IC IA L

Ph3P

Br Br C Br Br

Corey, E. J.; Fuchs, P. L. Tetrahedron Lett. 1972, 13, 3769

Corey-Fuchs reaction. A: Generation of a stable carbanion (cf. pKa CHCl 3 = 13.6). B: E2 elimination

(triphenylphosphine oxide is an extremely good leaving group). C: Halogen-lithium exchange follow by -

-elimination to generate an alkylidene carbene. D: C-H insertion of the carbene. E: pKa n-Bu = 50,

B050 Me Me

ArSO2NHNH2

KÈ

ẠY

Me Me

-H2O A

N H

SO2Ar BuLi

Me Me

Me Me O O N S N Ar

Me Me

SO2Ar

-SO2Ar

N H

SO2Ar

n-Bu Li

Me Me

B H Me Me n- u B Li

-N2

Me Me

C Me Me

Me Me

O Ph

Me Me

Me Me Ph Ph

Me Me

workup +H+

Me Me

Ph Ph

Me Me

Rupert, K. C.; Liu, C. C.; Nguyen, T. T.; Whitener, M. A.; Sowa, J. R.. J, Organometallics 2002, 21,144 Shapiro reaction. A: Formation of a hydrazone. B

-position of the hydrazone

anion. C: Elimination of a sulfinate ion ( pKa RSO2H = 1.5). D: Loss of N 2 to form an alkenyl anion.

+H+

-H+

CO2Me

+H+

NH2

CO2Me H2O

CO2Me H

CO2Me

HO HO

NH Ar

-H+

-CO2 -H+

H O O

IC IA L

B051

Konda, M.; Shioiri, T.; Yamada, S. Chem. Pharm. Bull. 1975, 23, 1025

A: Generation of a stabilized benzyl cation.

B: Decarboxylation to form an enol, an aldehyde

equivalent. C: Pictet-Spengler reaction ( ref A033).

OMe

KÈ

H H

B052

ẠY

MeO H

O O

H H

-HCO2Me O

C O

+H+ O

OH OH

MeO Shimada, K.; Kaburagi, Y.; Fuku yama, T. J. Am. Chem. Soc. 2003, 125, 4048.

A: pKa MeOH = 15.5, CH 3CHO = 16.7. (Cannizzaro-type reaction).

B: Aldol reaction.

C: Intramolecular hydride transfer

B053 O O

OMe

OMe Me

A N

O B

N N

OH O -H+

OH O Me

OMe

+H+

OMe

IC IA L

O Me

OMe

N N

1993, 420.

Brown, J. M.; Evans, P. L.; James, A. P. Org. Synth., Coll. Vol.

Morita-Baylis-Hillman reaction. A: Michael addition of DABCO. B: Aldol reaction. C: Elimination of

DABCO.

B054

CO2Me

N O

N H

-H2O A

OMe

ẠY

CO2Me C

KÈ

CO2Me

N CO2Me aq HCl

+ CO2Me -H

CO2Me

OH2

+H+

NH OH CO2Me

N H -H+

O CO2Me

H2 Pd/Al2O3 MeOH

O CO2Me

Burpitt, R. D.; Thweatt, J. G. Org. Synth., Coll. Vol.

1973, 277.

A: Formation of an enamine. B: A stepwise formation of the four-membered ring by means of Michael addition. C: Cleavage of the cyclobutene to release the ring strain.

B055

OEt

-TsHN-

OEt

OEt N N N Ts H

OEt N N N Ts

O Ph

N N N Ts

NEt3

N N

OEt

N N

IC IA L

Lall, M. S.; Ramtohul, Y. K.; James, M. N. G.; Vederas, J. C. J. Org. Chem. 2002, 67, 1536.

Regiz Diazo transfer reaction. A: pKa RCOCH 2CO2R = 11, HNEt3+ = 10.7. B: Attack on the less

hindered, electrophilic nitrogen. C: pKa PhSO2NH2 = 8.5:

t-BuO

B056

OEt

KÈ

H OEt

ẠY

-H+

OEt aq HCl S

H2N

H3N

OH2

OEt H2N

+H+ B

H EtO OH

-H+

H3N

O H3N

+H+ S

Dijkstra, D.; Rodenhuis, N.; Vermeulen, E. S.; Pugsley, T. A.; Wise, L. D.; Wikstrm, H. V. J. Med. Chem. 2002, 45, 3022. Neber rearrangement. A: Generation of a nitrene to form the azirine, which then undergoes addition of ethanol. B: Acidic hydrolysis of the ethoxyaziridine.

B057 Me

OEt H

NaOEt Br

O Br

Br Br

Br Me

OEt

CO2Et

IC IA L

A: Favorskii rearrangement ( ref

A069).

Marx, J. N.; Norman, L. R. J. Org. Chem. 1975, 40, 1602. B: Cleavage of the strained cyclopropanone with a

B058 O

KÈ

ẠY D

O O

I A

O OMe

Me O OH H

I B

O O

OH O

O H3C I

OH H

I O H2O

HCl

OMe

CO2Me

concurrent elimination of the bromide (formation of the thermodynamically more stable trans -ester).

O O

OMe

Shoji, M.; Yamaguchi, J.; Kakeya, H.; Osada, H.; Hayashi, Y. Angew. Chem. Int. Ed. 2002, 41,319; A: Iodolactonization. B: Hydrolysis of the lactone followed by formation of the epoxide.

B059 O MeO2C

O MeO2C

N H

H2C N N

MeO2C

HBr

ClCH3 + N2

H3C N N

IC IA L

H2C N N

MeO2C

-N2

O Br

MeO2C

Nair, V.; Jahnke, T. S. Tetrahedron 1987, 43 4257.

Excess diazomethane is needed to scavenge HCI.

B060

KÈ

OH N Me

ẠY

N Me H

O O

N Me H

O Me

Me H O

Me N Me H

O O

-AcOH

Me N O e M H

OAc

D N Me

Rueppel, M. L.; Rapoport, H. J. Am. Chem. Soc. 1978, 92, 5781. A: Formation of a mixed anhydride. B: pKa (CH 3CO)2O = 13.5. C acylation is faster than intermolecular one.

-Elimination. D: Intramolecular

B061

O 11

O EtO P EtO CN

NEt3 H

CN O P(OEt)2 OH O O

R A

OH O

-HCN

CO2t-Bu

H2N

H N

OH O

IC IA L

OH O

CO2t-Bu

Shioiri, T.; Terao, Y.; Irako, N.; Aoyama, T. Tetrahedron 1998, 54, 15701.

A: Formation of a mixed anhydride. B: Formation of the reactive acyl cyanide.

B062 O

N O

Cl4P Cl

Cl PCl4

N O

NH2

-HCl

Cl H

PCl3 Cl

Cl4P Cl

-HCl -POCl3

NH2

N O

NH2

Cl PCl3

-HCl -POCl3

CN N

Cl 1963, 166.

Taylor, E. C., Jr.; Crovetti, A. J. Org. Synth., Coll. Vol.

KÈ

A: Activation of the N-oxide with PCl 5. B: Dehydration of the amide.

B063

ẠY

O Me

O OMe

A Cl O NC

Me Cl O CN

OMe

O -H+

O OMe

-H+

B OMe Crimmins, M. T.; Siliphaivanh, P. Org. Lett. 2003, 5, 4641. A: Transfer of two electrons from the starting material to DDQ by forming a charge-transfer complex.

IC IA L

B: Deprotonation to form a p-quinonemethide-type intermediate.

N O S Cl O

OMe

O H

H N O S Cl O O

OMe DMF

OMe B

OMe

Me O N O Me O S N O

Me O N O Me O S N O -SO3 OMe -DMF

Me O N O Me O S HN O

N Me

A OMe

O Cl S N C O O

B064

OMe

-H+

OMe

Lohaus, G. Chem. Ber. 1967, 100, 2719.

OMe

A: Electrophilic substitution of an electron-rich aromatic compound. B: Attack on the oxygen of DMF.

KÈ

C: Cyclization followed by fragmentation to form the nitrile.

ẠY

B065

CO2H NH2

t-BuO N O

CO2H A N N O H

-H

+H+

N N OH

O N N OH2

O C N

C N

N N

IC IA L

H OH

-H+

N H

+H+

D Br

Rigby, J. H.; Laurent, S. J. Org. Chem. 1998, 63, 6742. A: Formation of a diazonium salt ( ref A037). B: Formation of a benzvne with a loss of CO2 and N2.

C: Nucleophilic addition of the isocyanide. D: Addition of water to the nitrilium ion.

B066 OAc I Ph OH

AcO

-AcOH

OAc I Ph O

OH NHCbz

ẠY

KÈ

OH NHCbz

CbzHN

-AcOH

NaHCO3

-PhI A

MeOH O CbzHN O

H -H+

+H+

OH OMe

CbzN

N H Cbz

CO2Me

MeO Wipf, P.; Li, W. J. Org. Chem. 1999, 64, 4576.

A: Oxidative lactonization of N-Cbz tyrosine. conjugated dienone.

B: Intramolecular Michael addition to the cross-

B067 O

N C CCl3 O

CCl3

CO2Me

-H+

CCl3

+H+

Me + NH2

TfOH CCl3

CO2Me

Me H

IC IA L

CCl3

White, J. D.; Reddy, G. N.; Spessard, G. O. J. Am. Chem. Soc. 1988, 110, 1624. A: Addition of benzyl alcohol to electron-deficient Cl 3CCN with a help of catalytic amount of base. B:

B068 H OH

+H+

ẠY

KÈ

Me H

-H+

OH2

O H

-H2O

O H

Me H

-H2O

M H

Me Me

Ftherification of alcohols under acidic conditions.

Me Me

-H+ B

O C

OH2 C O

OH D O

Koch, H.; Haaf, W. Org. Synth., Coll. Vol.

1973, 20.

A: Formation of a stable t-butyl cation. B: Generation of CO by dehydration of formic acid. C: Hydride abstraction from the bridgehead of adamantane. D: Addition of CO to form an acylium ion.

B069 t-BuO

-H+

IC IA L

Hauser, C. R.; Kantor, S. W. J. Am. Chem. Soc. 1951, 73, 1437.

[1,2] Wittig rearrangement. A: pKa PhCH 3 = 41, n-BuH = 50. B: Homolytic cleavage to form a radical

anion. C: A facile radical recombination in a solvent cage.

B070 Ph

H H

OMe -PhCN Ph B

CO2Me

O N

O C H

OMe

+H+

CO2Me O

workup

Gómez, V.; Perez-Medrano, A.; Muchowski, J. M. J. Org. Chem. 1994, 59, 1219

n-Bu3SnH

n-Bu3Sn

n-Bu3SnS

AIBN

ẠY

KÈ

B071

A: Michael addition of an oxime anion. B: Intramolecular deprotonation to cause fragmentation.

O O

n-Bu

n-Bu Me

O n-Bu

H Me

n-Bu3Sn H

- n-Bu3Sn

D OH

Rawal, V. H.; Newton, R. C.; Krishnamurthy, V. J. Org. Chem. 1990, 55, 5181. A: Barton-McCombie deoxygenation ( ref A051).

B: Cleavage of the strained epoxide ring. C:

IC IA L

Intramolecular abstraction of a hydrogen via a six-membered transition state. D: 5-exo-trig Radical cyclization.

B072

Br SO2CH2Br

t-BuOK

-SO2CH2Br

SO2CH2Br

O r B S O

SO2CH2Br

-SO2

Ot-Bu

Ot-Bu H CH2 S O O

SO2CH2Br

KÈ

S O O Block, E.; Aslam, M. Org. Synth., Coll. Vol.

1993, 212.

A: Photo-induced homolytic cleavage to form a sulfinyl radical. B: Addition to the olefin to form a

ẠY

stable tertiary radical. C: Attack on the bromide of the reagent (radical chain reaction). D: Elimination

of HBr followed by vinylogous Ramberg-Bäcklund reaction.

B073 Me

Me KNH2

Br +

hv A

Br +

IC IA L

Me D

Rossi, R. A.; Bunnett, J. F. J. Org. Chem. 1973, 38, 3020.

SRN1 reaction. A: SET to bromobenzene to form a radical anion. B: Fragmentation of the radical

anion to form a phenyl radical. C: Addition to enolate to form a radical anion. D: SET to continue the

B074

KÈ

radical chain reaction.

ẠY

Bu N F3B

O O

-CO2

Bu F3B

O N

F3B Bu N CH2

CH2

N F3B Bu O N N

F3B Bu

F3B Bu N

S F

N S

workup

Bu N

N S

Newcomb, M. Ha, C. Tetrahedron Lett. 1991, 32, 6493. A: Photo-induced homolytic cleavage. B: Decarboxylation to form an aminyl radical. C: Acti vation of the aminyl radical by Lewis acid. D: Kinetically fa vored 5-exo-trig radical cyclization.

E: Group

transfer reaction.

H CBr3

t-BuO

-Br-

CBr2 Br

CBr2

Me C

Br Br

Me Me

-Br-

Me Me

MeLi

Br Br

CBr2

IC IA L

B075

Me E

1990, 200.

-Elimination to form dibromocarbene. C: Cyclopropanation of the more

A: pKa CHCl 3 = 13.6.

Taylor, R. T.; Paquette, L. A. Org. Synth., Coll. Vol

electron-rich, tetrasubstituted olefin. D: Halogen-

-elimination to

form a carbene. E: C-H insertion of the carbene (the corresponding allene cannot be formed due to

the excessive ring strain. ref A061).

B076

KÈ

Cl Cl

OEt

ẠY

Cl Cl

O OEt

OMe

OMe Cl

Cl Cl

-Cl-

Cl D Cl

Jefford, C. W.; Gunsher, J.; Hill, D. T.; Brun, P.; Gras, J. L.; Waegelt, B. Org. Synth., Coll Vol.

1988, 142.

A: pKa CHCl 3 = 13.6. B: Generation of dichlorocarbene. C: Cyclopropanation from the sterically less hindered exo-side. D: 2e Disrotatory electrocyclic reaction to form an allyl cation.

B077 O -CO2

Cl Cl

H Cl

OAc

Cl Cl

OAc

Ac2O Cl

Cl Cl

MeLi

OMe

CCl3

IC IA L

Cl Cl

workup

+H+

Wang, Z.; Campagna, S.; Xu, G.; Pierce, M. E.; Fortunak, J. M.; Confalone, P. N. Tetrahedron Lett. 2000, 41, 4007.

A: pKa CHCI3 = 13.6. B: Reduction with Zn to form a gem-dichloroolefin. C: Corey-Fuchs-type

B078 H

-H+

H2O

KÈ

alkynylation ( ref B049).

H N

SiMe3 H N

ẠY

H2N Bn

Me3Si

OH2 H NHBn

OH2

-H2O NBn

NHBn

SiMe3

OH2

-H+ +H+

-H+

NBn

C H

NBn H

Larsen, S. D.; Grieco, P. A.; Fobare, W. E J. Am. Chem. Soc. 1986, 108, 3512. A

-carbocation). B:

Desilylation to form an olefin. C: Olefin-iminium ion cyclization to form a stable tertiary carbocation.

B079 O O S N NH2 NO2 H CO2Et N N EtO2C PPh3

O O S N NH2 NO2 O PPh3

- Ph3P O

CO2Et HN N EtO2C

O PPh3

O S N O NH2

N N

-N2 D H

Myers, A. G.; Zheng, B. Tetrahedron Lett. 1996, 37, 4841.

-ArSO2H

O2N

IC IA L

CO2Et N N EtO2C Ph3P

CO2Et HN N EtO2C PPh3

A: Mitsunobu reaction ( ref A045). B: Deprotonation of the more acidic proton. C: Elimination of a

KÈ

B080

sutfinate ion. D: Elimination of N2 via a concerted mechanism.

PPh3

CO2Et NO2

NO2

CO2Et NO2

PPh3 CO2Et

CO2Et

ẠY

NO2

CO2Et

P(OEt)3 N O

B P(OEt)3

CO2Et

N O O P(OEt)3

CO2Et C N

P(OEt)3

N H

CO2Et

CO2Et A

H CO2Et

N H

CO2Et

IC IA L

CO2Et

Mali, R. S.; Yadav, V. J. Synthesis 1984, 862.

A: Wittig reaction. B: [4+2] Cheletropic reaction and elimination of a phosphate to form a nitroso intermediate. C: Deoxygenation of the nitroso compound to form a nitrene. D: Formation of the

indole could be interpreted as a result of either 1) a direct C-H insertion or 2) formation of the azirine

followed by homolytic cleavage and recombination of the resulting diradical.

OH2

-H

ẠY D

-H2O

O N

+H+

H2N

N N

KÈ

O N

B081

H Me

O N

CO2H H Me

-H

+H+

N HN

-N2

A Cl

H O

-H+

CO2H H Me

+H+

OH2 CO2H H Me

O Me

Cl B

CO2H H Me

Koppenhoefer, B.; Schurig, V. Org. Synth., Coll. Vol A

N N

-lactone via a diazonium salt. B

1993. 119 -lactone with

-position is retained as a result of the double inversion.

B082 O CO2Et

Me MeO

NaNO2

HCl A

NH2

KOH

N N

IC IA L

MeO

O MeO

CO2Et

MeO

OH Me O

Et N N

HO H MeO

N N H

aq HCl

MeO

CO2Et

Q M

KÈ ẠY

-H+ +2H+

CO2Et N H NH3

-NH3

MeO

-H

N H

CO2Et

Zhao, S.; Liao, X.; Wang, T.; Flippen-Anderson, J.; Cook, J. M.

N H

CO2Et

MeO

+2H+

Me H

-H

NH NH2 2

MeO

-H+

Y U CO2Et

CO2Et

NH NH

N N H H

MeO

N N H H

CO2Et EtOH 65oC

MeO

Et OEt

N N

Japp-Klingemann reaction and Fischer indole synthesis.

Addition of the enolate to the diazonium salt. C D: Fischer indole synthesis ( ref B031).

J. Org. Chem. 2003, 68, 6279. A: Formation of a diazonium salt.

-ketoester to form a hydrazone.

B083 O N

N Ph

A C6H13

C6H13

B(C6H13)2

O Ph B(C6H13)2

Ph C6H13

-N2 B

B(C6H13)2

(C6H13)2B

workup

C6H13

IC IA L

C6H13

+H+

Kono, H.; Hooz, J. Org. Synth., Coll. Vol.

B: Elimination of N2 with a

A: Attack of a diazoketone to B(n-hexyl)3 to form an ate complex.

1988, 919.

simultaneous migration of n-hexyl group. C: Formation of a boron enolate.

H2O OMe

-H

+H+

i-Bu

-H+ H

i-Bu MeOH

HOMe

OMe

B084

MeO OMe Me

U Q

OMe

ẠY

KÈ

i-Bu

MeO

OMe

A i-Bu

i-Bu

HOMe

HOMe OMe C

i-Bu

MeO OMe I AgNO3

I -H+

OMe

i-Bu

-MeOH

i-Bu

OMe

-H+

OMe MeO OMe

i-Bu OH2

H2O +H+ D

OMe i-Bu

MeO OMe H

OMe i-Bu

OMe

-H+ +H+

OMe

HO OMe H

i-Bu

Oppolzer, W.; Rosset, S.; Brabander, J. D. Tetrahedron Lett. 1997, 38, 1539. A: Iodination of the enol ether with concomitant formation of a dimethyl acetal. B: Activation of the iodide with a silver ion to form a phenonium ion. C: Restoration of the aromaticity causes a cleavage

IC IA L

of the electron-rich cyclopropane ring. D: The orthoester thus formed undergoes a facile hydrolysis to give the ester.

O S O O

O -AcOH AcO S OH A O

O HO S OH O

O AcO

B085

-H+

OH O S OH O

O SO3H

OH SO3H

KÈ

Bartlett, P. D.; Knox, L. H. Org. Synth., Coll Vol

1973, 194.

A: Generation of SO3. B: Wagner-Meerwein-type rearrangement. C: Sulfonation of the olefin to form

ẠY

a stable tertiary carbocation.

B086

OMs Me

OMs Me A

H2B

OMs Me

NaOH H2O

H2B

(HO)3B

H Me

H (HO)3B

OMs H

H Marshall, J. A.; Bundy, G. L. J. Am. Chem. Soc. 1966, 88, 4291.

B087 Br Br

Me Br

A Me

t-BuOK

O C

B Me

O Br

t-BuO

IC IA L

A: Hydroboration from the less hindered side. B: Grob fragmentation ( ref B016).

t-BuO

Paquette, L. A.; Barrett, J. H. Org. Synth., Coll. Vol

1973, 467.

A: Bromination of the olefin. B: Dehydrobromination to form a diene. C: 6e Disrotatory electrocyclic

reaction (valence isomerism).

KÈ

B088

-H+

N H

H N

+H+

N N N

ẠY D N

N N

-H+

A N

-N2 B N

C N

Golka, A.; Keyte, P. J.; Paddon-Row, M. N. Tetrahedron 1992, 48, 7663. A: Inverse electron demand Diels-Alder reaction. B: Retro Diels-Alder reaction. C: Aromatization.

B089 N

NEt3

O H H

H OH

N O

N Cl

NEt3

Cl OH

O H

IC IA L

Cl O

Lee, G. A. Synthesis 1982, 508.

A: Chlorination of an oxime. B: Elimination of chloride ion is facilitated by the formation of an oxime

anion. C: Generation of a nitrile oxide. D: 1,3-Dipolar cycloaddition.

O A

O N

B090

N Ph

Y U

KÈ

AcO

ẠY

O N

N H

O C

AcO

O Me

N Me

+H+ O

or Me

N Ph

O C NPh

Et3N

O N

-CO2

Ph N C O Ph NH2

-H+ +H+

O Ph

N H

Mukaiyama, T.; Hoshino, T. J. Am. Chem. Soc. 1960, 82, 5339. A: pKa CH 3NO2 = 10.2,

+ HNEt3

= 10.7. B: Addition of the nitronate to PhNCO. C: Formation of the

nitrile oxide might proceed either by 1) syn-elimination of the carbamate ion or 2) elimination of the carbamate ion followed by deprotonation. D: 1,3-Dipolar cycloaddition.

B091 Me

EtO EtO H

+H+

H3C OEt

CH3

O H

H EtO

EtO

EtO R

EtO

O C

-H+

-EtOH

Me EtO

OEt

-H+

OEt -EtOH H3C OEt OEt H

+H+

IC IA L

OEt H3C OEt OEt

Johnson, W. S.; Werthemann, L.; Bartlett, W. R.; Brocksom, T. J,; Li, T.-t. J. Am. Chem. Soc. 1970, 92, 741.

Claisen-Johnson rearrangement. A: Acid-catalyzed ether exchange of the orthoester. B: Formation of the mixed ketene acetal is effected by removal of ethanol from the reaction system by distillation. C:

[3,3] Sigmatropic rearrangement via a chair-like transition state to form an (E)-olefin.

B092 H

-H+

HN n-Pr Me OMe

+H+

KÈ

OMe Me

OH2

N n-Pr Me OMe

ẠY D

N n-Pr

-H+ OH2

+H+

N n-Pr

H O H MeO Me

MeO

OMe Me A

O -H+ -MeOH

Me Ph

N n-Pr

Overman, L. E.; Kakimoto, M.; Okazaki, M. E.; Meier, G. P. J. Am. Chem. Soc. 1983, 105, 6622.

A: Aza-Cope rearrangement. B: Intramolecular Mannich reaction.

B093 t-Bu

OTf Si Me Me

Me Me Si t-Bu O

Et3N H

OTBS

OMe

OMe OMe H B

TBSO

OMe H

OMe

Me HO t-Bu Si Me O H2O

OMe

HO2C

H3O

OSBT

OMe

TBSO

IC IA L

Nakatsuka, M.; Ragan, J. A.; Sammakia, T.; Smith, D. B.; Uehling, D. E.; Schreiber, S. L. J. Am. Chem. Soc. 1990, 112, 5583.

Claisen-lreland rearrangement. A: Formation of a ketene silyl acetal. B: [3,3] Sigmatropic

rearrangement via a boat-like transition state.

B094 Me

KÈ

H Me

ẠY

workup

O S

+H+ O

O S

Me Ph

A O

150oC

Me B

O S

CHO

O Saito, M.; Kawamura, M.; Ogasawara, K. Tetrahedron Lett. 1995, 36, 9003. A: Conjugate addition to the vinyl sulfoxide. B: syn-Elimination. C: Claisen rearrangement.

B095 Br S

n-BuLi

HgCl2

S S

H2O C

CHO

S Hg Cl

H2O

S Hg Cl

HgCl S

-H

Cl Hg Cl

IC IA L

n-Bu

Hunt, E.; Lythgoe, B. J. Chem. Soc., Chem. Commun. 1972, 13, 757. A: Formation of a sulfonium ion. B: Deprotonation to form a sulfur ylide, which undergoes [2,3]

sigmatropic rearrangement. C: Hydrolysis of the thioacetal.

B096 H

KÈ

Me O

ẠY

H N

CO2Et

CHO Br

CHO

H N

CO2Et

CO2Et Me -H+

+H+

CO2Et Me

CO2Et

A O

N H

B O

Bashiardes, G.; Safir, I.; Mohamed, A. S.; Barbot, E; Laduranty, J. Org. Lett. 2003, 5, 4915. A: Formation of an azomethine ylide. B: Intramolecular 1,3-dipolar cycloaddition.

B097

AcO

H Me O

OAc

O C

-H

+H+ E

H Me OH

AcO

OAc

H Me OH

AcO

NOH

AcO

OAc

N O

AcO AcO Me

O N

H Me O

O N

AcO

OAc

N O

AcO AcO Me

AcO Me

AcO

H Me O H Cl

AcO

IC IA L

AcO

Murai, A.; Nishizakura, K.; Katsui, N.; Masamune, T. Tetrahedron Lett. 1975, 16, 4399.

Barton reaction. A: Formation of a nitrite. B: Homolytic cleavage. C: Abstraction of a hydrogen atom via a six-membered transition state. D: Recombination of ,NO with the resulting radical.

Tautomerization.

O C

O O

ẠY

O Ph

KÈ

B098

O N O

OH -H+ +H+ D

Barltrop, J. A.; Plant, P. J.; Schofield, P. Chem. Commun. 1996, 822. Photo-cleavable protecting group for acids.

A: Photo-activated formation of a diradical.

Intramolecular abstraction of a hydrogen atom. C: Recombination of the diradical. D: Elimination of benzoic acid.

B099

A O P(OEt)2

O O

O O P(OEt)2

IC IA L

O P OEt)2 H2C (

P(OEt)2 O

O P(OEt)2

Altenbach, H.-J.; Holzapfel, W.; Smerat, G.; Finkler, S. H. Tetrahedron Lett. 1985, 26, 6329.

A: Addition to the reactive enol lactone. B: Intramolecular Horner-Wadsworth-Emmons reaction ( ref

A071 ).

B100

CHO

O N

PPh3 Br

CHO N H

O PPh3

PPh3

Schweizer, E. E.; Light, K. K. J. Org. Chem. 1966, 31, 870.

A: pKa of the parent indole NH = 17, H 2 = 35. B: Addition to the vinylphosphonium salt to form an ylide.

KÈ

C: Intramolecular Wittig reaction.

B101

ẠY

N N N

-N2

H Ph

H Ph Ph3P O

NH2 H Ph

PPh3 N

HO Ph

H Ph

Ph3 P H OR NH O Ph

PPh3 Ph

-H+ +H C

N N N PPh3

PPh3

-Ph3P=O D

H Ph

H N

H Ph

Pöchlauer, P.; MüIler, E. P.; Peringer, P. Helv. Chim. Acta 1984, 67, 1238. Staudinger reaction (A-B).

A: Cheletropic reaction.

B: Formation of an iminophosphorane. C:

Migration of the phosphorus group. D: Intramolecular SN2 reaction.

B102

H Ph

+ H +H Ph

H Ph

Ph3P HO Se

IC IA L

H Ph

Se PPh3

SeH

H Ph

Ph3P O

Se H -Se Ph D

H Ph

-H+ -Ph3P=O

+H+ B

PPh3 O SeH

-H+

Ph3P Se

Clive, D. L. J.; Denyer, C. V. J. Chem. Soc., Chem. Commun. 1973, 253. B: Migration of the

A: Acid-catalyzed cleavage of the epoxide with inversion of configuration.

phosphorus group. C: Intramotecular SN2 reaction with inversion of configuration to form a cis-

episelenide. D: Spontaneous extrusion of selenium.

OH N

+H+

N HO

-H+

S N

B103

KÈ

-H+

ẠY

+H+

S O

P(OMe)3

A Ph

S P(OMe)3 O Ph

O Ph

O B

O Ph

-CO2 C

O Ph

P(OMe)3

S O

P(OMe)3 O

P(OMe)3

O C

-CO2 -P(OMe)3

Corey, E. J.; Winter, R. A. E. J. Am. Chem. Soc. 1963, 85, 2677.

IC IA L

Corey-Winter olefination. A: Formation of a thionocarbonate. B: Reductive desulfurization of the thionocarbonate to generate a carbene.

C: The resulting carbene might undergo a direct

fragmentation to form the cis-olefin. Alternatively, it would react with a phosphite to form an ylide,

which then collapses to give the product.

B104 SiMe3 O A

H C8H17

C8H17

H C8H17

C8H17

H C8H17 I

SiMe3 H Me3Si O

C8H17

Me3Si

Me3Si O

O C8H17

I SiMe3

C8H17

Denis, J. N.; Magnane, R.; Eenoo, M. V.; Krief, A. Nouv. J. Chim. 1979, 3, 705.

A: Silylation of the epoxide. B: SN2 reaction with inversion of configuration. C: Silylation of the silyl

ether. D: E2 elimination.

B105

KÈ

OMOM

C6H13

PdLn A

ẠY

Si Me Me

-PdLn C

Me Ln Si O Pd H

C6H13

Si Me Me

Ln MOMO Pd H C6H13

OMOM H Ln

MOMO H C6H13 O

Si Me Me

B C6H13

H OMOM

OMOM

H2O2 KOH C6H13 O

OOH Si Me Me

OMOM

C6H13

OMOM

C6H13 O

Si O OH Me Me

workup O

O Si Me Me

C6H13 OH OH

+H+

Tamao, K.; Nakagawa, Y.; Arai, H.; Higuchi, N.; Ito, Y. J. Am. Chem. Soc. 1988, 110, 3712.

IC IA L

Tamao oxidation (D-E). A: Oxidative addition to the Si-H bond. B: Intramolecular diastereoselective

silametallation to the olefin. C: Reductive elimination. D: Formation of a silicate ion. E: Migration of the Si-C bond.

NEt3

Me Me SPh

B Me

SPh O

Me Me

Me O

Me Me

Me O

Me O H Me

PhS Cl

Me Me

B106

Okamura, W. H.; Peter, R.; Reischl, W. J. Am. Chem. Soc. 1985, 107, 1034.

A: [2,3] Sigmatropic rearrangement of the propargyl sulfenate. B: 6e Disrotatory electrocyclic reaction.

B107

KÈ

MeO Me

ẠY

I2Sm

OMe

SmI2

O MeO Me

O Me

I2Sm

SmI2

O Me

MeO Me

I O

SmI2

O O Me

I2Sm

SmI2

I2Sm

SmI2 HO

workup

+H+

Molander, G. A.; Harris, C. R. J. Org. Chem. 1997, 62, 2944

IC IA L

A: Since Sml 2 is a single electron reductant, two molecules of Sml 2 are needed to convert an alkyl

iodide to the corresponding organosamarium species. B: SET to the ketone followed by radical

cyclization.

OMe

MeO Me

TfO Hg TfO

TfOHg

OMe

TfO Hg

KÈ

TfO TfO Hg

MeO Me

OMe

TfO Hg

MeO Me

OMe

H Me MeO Me

OMe

D H Me

H Me

H Imagawa, H.; lyenaga, T.; Nishizawa, M. Org. Lett. 2005, 7, 451.

ẠY

OMe

MeO Me

B108

A: Coordination of Hg(OTf)2 to the alkyne.

B: 6-endo-dig cation cyclization to form a stable

tertiarycarbocation. C: Attack of the electron-rich aromatic ring to the carbocation.

of the C-Hg bond to regenerate the catalyst.

D: Protonolysis

B109

MeO2C

RuLn

MeO2C

MeO2C LnRu

- Ph

LnRu

O H

RuLn R

MeO2C

LnRu

IC IA L

MeO2C

Kinoshita, A.; Mori, M. J. Org. Chem. 1996, 61, 8356.

Intramolecular enyne metathesis ( ref A078). A: Intermolecular alkene metathesis. B: Intra-

molecular alkyne metathesis.

B110 CHO

N H

O CHO

SMe2

KÈ

Na3N

ẠY

SMe2 N3

+H+

N O

N3 N

Wang, Y.; Zhang, W.; Colandrea, V. J.; Jimenez, L. S. Tetrahedron 1999, 55, 10659. A: pKa indole NH = 17, H 2 = 35.

B: Addition of the vin ylsulfonium salt to form an ylide.

Intramolecular addition to the aldehyde (reversible). D: Intramolecular SN2 reaction to form an epoxide. E: Cleavage of the epoxide helped by the indole nitrogen lone pair.

B111 n=1

OH A

-N2

O Me

N HN

O Me

-N2

+H+ C

H N

n=3

IC IA L

NH Me

NHPh

Wrobleski, A.; Aube, J. J. Org. Chem. 2001, 66, 886.

Intramolecular Schmidt reaction. A: Acti vation of the carbonyt group by protonation followed by

intramolecular addition of the azide (six-membered ring is easy to form). B: Ring contraction. C: The D:

formation of a phenonium ion is preferred over the formation of the eight-membered ring.

Intramolecular Mannich reaction.

O Tol S S O

ẠY

KÈ

B112

STs

S H

STs

S O S O Tol

NEt3

Et3N H

S S

aq HCl H S

H2O S

S S

H2O

-H

N H S

+H+

N H

-H+

Woodward, R. B.; Pachter, I. J.; Scheinbaum, M. L. Org. Synth., Coll. Vol.

1988, 1014.

IC IA L

A: pKa PhSO2H = 1.5. B: Formation of an easy to form six-membered ring. C: Hydrolysis of the enamine.

NAc

t-BuO H

NAc

Me N

N U

Ph O

M KÈ

Ph H Ot-Bu O NAc

H O

OAc

NAc

AcO

NAc

Ph H N

NAc

AcO

NAc

Ph Me O

O H

AcN

O Me

Ot-Bu

B113

NAc

Gallina, C.; Liberatori, A. Tetrahedron Lett. 1973, 1135.

-position of an imide (more acidic than amides). B: Aldol reaction followed by

an intramolecular acyl transfer via a five-membered ring transition state. C: Elimination of the acetoxy

ẠY

group.

B114

O Me

N Me

Me A

O C

N Me

R Me

H C

Me2N

O R

-H+ +H+

Me N Me O

R O

C H

O Me N Me

Me N Me

OH Me

toluene

Me N Me

OH Me

CSA

IC IA L

Me N Me

Gais, H. J. Tetrahedron Lett. 1984, 25, 273. A: Protonation of the carbonyl group followed by addition of the carboxylate to the iminium ion. B:

Intramolecular acyl transfer to form a vinylogous anhydride. C: Acti vation of the vin ylogous anhydride

by protonation resulted in the formation of the macrocyclic lactone.

B115 OEt

OEt

ẠY D

O SiMe3

e O

EtO

OEt

KÈ

OEt

O O

OEt

O O

OEt

Me3Si Cl

C O

O SiMe3

Me3Si Cl

Bloomfield, J. J.; Nelke, J. M. Org. Synth., CoIl Vol. Acyloin condensation.

OSiMe3 OSiMe3 1988, 167.

A: Single electron transfer (SET) to the carbonyl group followed by

lactonization. B: SET followed by a ring contraction. C: SET followed by silylation. D: SET to form an enolate followed by silylation.

B116 O

O HO

MeOH H O

TsOH H

OMe

O O

MeOH OMe

OMe

+H+ F

Me2S E

OMe

NaHCO3

OMe

-MeOH

-H+

OMe

OMe Me2S

-H+

+H+

OMe MeOH

-H+

+H+ C

IC IA L

O O

-H+

OMe

Claus, R. E.; Schreiber, S. L. Org. Synth., CoIl Vol.

1990, 168.

A: 1,3-Dipolar cycloaddition of ozone to the olefin. B: Heterolytic cleavage of the initial ozonide. C: Trapping the dipole with methanol. D: Formation of a dimethyl acetal from the aldehyde (protonation

of the less electron-dense hydroperoxy group is more difficult). E: Neutralization to kill TsOH. F:

Reduction of the hydroperoxide with dimethyt sulfide.

B117 O

O O

KÈ ẠY

D O OMe

O O

R O

OMe

NEt3 Me

Et3N

+H+ C

NEt3

Ac2O OH

OMe

O O

MeOH

-H+

OMe

O O

O Me

O OMe

OMe

NEt3

H O

O O

OMe

H R MeO

O O

IC IA L

or O

OMe

1990, 168

Claus, R. E.; Schreiber, S. L. Org. Synth., CoIl VoL

A: 1,3-Dipolar cycloaddition of ozone to the olefin. B: Heterolytic cleavage of the initial ozonide. C: Trapping the dipole with methanol. D: Acetylation. E: Elimination of acetic acid might proceed either

by 1) deprotonation with triethylamine, 2) Baeyer-Villiger-type 1,2-hydride shift, or 3) thermal eliminatior

via a six-membered transition state.

B118 A

AIBN

H X=Cl or I

n-Bu3SnH

n-Bu3Sn X

OEt

KÈ

OEt

O -t-Bu

ẠY

O B

OEt

Snn-Bu3 -n-Bu3SnI

n-Bu3Sn

H C N

C N

Me Me Me

t-Bu

Stork, G.; Sher, P. M. J. Am. Chem. Soc. 1986, 108, 303.

A: Reduction of Bu 3SnX with NaBH3CN to form a low concentration of Bu 3SnH to avoid the premature reduction of the radical intermediates. B: 5-exo-trig Radical cyclization. C: Addition to the isocyanide followed by elimination of a stable t-butyl radical.

B119

N N N

F3B O

N N OBF3

-N2

OBF3

IC IA L

N O

BF3

Lang, S.; Kennedy, A. R.; Murphy, J. A.; Payne, A. H. Org. Lett. 2003, 5, 3655.

A: Generation of a stable benzylic carbocation. B: Intramolecular attack of the azide. C: formation

ofan aziridine. D: Restoration of the aromaticity. E: 1,2-Alkyl shift.

B120

N O H

O Me N

N O

NEt3

O Ph

ẠY

O Me

KÈ

N O

D O

Quadrelli, P., Mella, M.; Invernizzi, A. G.; Caramella, P. Tetrahedron 1999, 55, 10497.

A: Elimination of chloride ion is facilitated by the formation of an oxime anion. B: Addition of NMO to

the nitrile oxide. C: Generation of an acylnitroso compound. D: Hetero-Diels-Alder reaction.

B121 H O

-H+ +H+ A

O B

H O

-H+

+H+ A

Drouin, J.; Leyendecker, F.; Conia, J., M. Tetrahedron. 1980, 36, 1203.

IC IA L

A: Tautomerization. B: Oxy-ene reaction.

B122 Me

N N

Cl Me

SO2

N N

NEt3 Me

O S O CH2 O

-N2

95oC

-SO2

SO2

SO2 1973, 877.

B: 1,3-Dipolar cycloaddition of diazomethane to the sulfene.

A: Generation of a sulfene.

Fischer, N.; Opitz, G. Org. Synth., Coll. Vol.

ẠY

KÈ

B123

Extrusion of N 2 to form an episulfone. D: Ramberg-Bäcklund reaction.

PPh3Br A

H t-BuO K

PPh3

O PPh3

PPh3 C

Ph + PPh3

IC IA L

Dauben, W. G.; Ipaktschi, J. J. Am. Chem. Soc. 1973, 95, 5088. A: Generation of an ylide.

B: Michael addition.

C: Regeneration of a phosphorus ylide.

Intramolecular Wittig reaction (irreversible). E: The unstable diene was trapped as the Diels-Alder

product.

B124 OTBS

Cl SePh

Me O

OTBS

PhSe

O Sit-BuMe2

KÈ

H Ph O Se Me

aq H2O2

O H

Ph O Se Me

H H

PhSe

HO OH

Me O

PhSeCl

-PhSeOH

C H

ẠY

Curran, D. P.; Rakiewicz, D. M. Tetrahedron 1985, 41, 3943,

A: Claisen-lreland rearrangement. B: Selenolactonization. C: syn-Elimination of the selenoxide.

B125

Ph Ph

S H B

O hv

Cl O

H Ph

HO B

S S

Vedejs, E.; Eberlein, T. H.; Ma zur, D. J.; McClure, C. K.; Perry, D. A.; Ruggeri, R.; Schwartz, E.; Stults, J. S.; Varie, D. L.; Wilde, R. G.; Wittenberger, S. J. Org. Chem. 1986, 51, 1556. A: n-

B: Intramolecular abstraction of a hydrogen atom

IC IA L

Norrish type II reaction.

followed by fragmentation to form a highly reactive thioaldehyde. C: Hetero-Diels-Alder reaction.

B126 Me

AcO

RuLn

N N

AcO

Me O

1991, 2565.

B: C yclopropanation of the aromatic ring. C: 6e

Disrotatory electrocyclic reaction.

AcO

Kennedy, M.; McKerve y, M. A. J. Chem. Soc., Perkin Trans. A: Formation of a rhodium carbene complex.

-N2

AcO

-RuLn

Me RuLn N N

B127

-CO

OMePh

KÈ

OMe

ẠY

(CO)4Cr

OMe Ph

OMe

OMe Ph

B (OC)3

Ph C O

OMe

Ph Cr(CO)3 Ph

(CO)4Cr

Cr(CO)5

(OC)3

Ph O

OMe

Ph Cr(CO)3 Ph

D H

C Cr

Ph Cr(CO)3 Ph OH

Dötz, K. H. Angew. Chem. Int. Ed. Engl. 1975, 14, 644. Dötz reaction. A: Alkyne metathesis of Fischer carbene complex. B: Insertion of CO. C: Reductive elimination to form a ketene. D: 6e Electrocyclic reaction.

B128 Et MgBr Et

H Ti(Oi-Pr)2

-EtH C

Ti(Oi-Pr)2

MeO

O D

Ti(Oi-Pr)2

MeO OMe Ti(Oi-Pr)2

Ti(Oi-Pr)2 O 2EtMgBr

Ti(Oi-Pr)2

OMe Ti(Oi-Pr)2

OMgBr workup Me

Et MgBr OMe

Ti(Oi-Pr)2

IC IA L

i-PrO Ti Oi-Pr)2 i-PrO (

+H+

Et Ti(Oi-Pr)2 Et

A: Substitution of the isopropoxide with EtMgBr.

Kulinkovich reaction.

Kulinkovich, O. G.; Sviridov, S. V.; Vasilevski, D. A. Synthesis 1991, 234.

a titanium

Reductive elimination to form

-Elimination.

ethylene complex (or a titanocyclopropane).

ẠY

KÈ

Carbotitanation. E.: Formation of a cyclopropane. F: Regeneration of the active reagent.

ẠY M

KÈ Y

Q H

N Ơ N

IC IA L

C001 H OMe O

MeO O

OMe OMs

Me H

H OMs

t-Bu

Me H

IC IA L

t-Bu

O MeO

t-Bu MeO

OMe

MeO OMe OH

Me H

t-Bu

Me H

Yamauchi, T.; Hattori, K.; Nakao, K.; Tamaki, K. Bull. Chem. Soc. Jpn. 1987, 60, 4015.

A: Formation of an epoxide by intramolecular SN2 reaction of a hemiacetal. B: E1-like cleavage of the

reactive epoxide.

C002

NO2

NEt3

NO2

O2N

KÈ N H

N H

OMe

NO2 O

O2S

Cl O2S

N H

O2S

O2N

N O O2S

NO2 O

O A N

N O OO S N Ar O H

ẠY

NEt3

O2N

-SO2

O O2N O

N S

OMe

O2N

O Huber, V. J.; Bartsch, R. A. Tetrahedron 1998, 54, 9281.

Smiles rearrangement. A: Addition-elimination process via a Meisenheimer complex.

C003

Et Me

O TiCl 4

Cl4TiO

workup

Me Et

Me O TiCl4

Me O

IC IA L

O TiCl4 Me

Bender, J. A.; Arif, A. M.; West, E G. J. Am. Chem. Soc. 1999, 121, 7443.

Cation-olefin cyclization initiated by Nazarov reaction ( ref B026).

BrMg

O A

OMgBr

OMgBr +H+

O workup

BrMg

C004

Kato, T.; Kondo, H. ; Nishino, M.; Tanaka, M.; Hata, G.; Miyake, A.

Bull. Chem. Soc. Jpn. 1980, 53, 2958.

-substituent. B: 1,2-Alkenyl

KÈ

shift. C: Anion-accelerated oxy-Cope rearrangement via a chair-like transition state.

ẠY

C005

EtO

TfO

Ph Ph Si

EtO A

Ph Ph Si OTf

EtO

prydine

Ph Ph Si H

O Me

Ph Ph Si OTf

EtO O

-H+

EtO2C Me

120oC SiPh2 O

SiPh2 O

EtO2C Ph Ph H Me Si H O

TBAF H2O2 C

SiPh2 F OH

CO2Et F O SiPh2F

OOH

CO2Et O OH SiPh2

+H+

CO2Et OH

CO2Et

+H+

EtO2C Ph Ph Me Si O

IC IA L

EtO2C

Sieburth, S. M.; Lang, J. J. Org. Chem. 1999, 64, 1780.

A: Protodesilylation to form a silyl triflate. B: Intramolecular Diels-Alder reaction. C: Tamao-Fleming

oxidation.

C006

NHTs

NHTs TsNHNH2

ẠY

NTs

N Ts

NTs

-ArSO2

B N

NHTs

KÈ

NaH

TsN H

N N S

N H Ts

N Ts

O O

-N2 H

N N

N Ts

OH N Ts

N Ts

Kim, S. H.; Fuchs, P. L. Tetrahedron Lett. 1996, 37, 2545.

IC IA L

A: Cleavage of the epoxide helped by the hydra zone anion. B: Conjugate addition of the sulfonamide

anion.

C007 O H

-H

N H

+H+

NH2

-H2O

Y Me

KÈ -H+

ẠY

+H+ B

Me Me

O O

H N t-Bu

t-Bu H N O

N H

t-Bu N C

OH Me

O Me

H N

N Ph

t-Bu

O Me

Semple, J. E.; Wang, P. C.; Lysenko, Z.; Joullie, M. M. J. Am. Chem. Soc. 1980, 102, 7505.

Ugi reaction (four-component condensation, 4CC). A: Most likely, addition of the isocyanide to the iminium ion and addition of the benzoate ion to the ensuing nitrilium ion takes place simultaneously. B:

Intramolecular acyl transfer reaction (the benzoyl group is activated).

C008 OMe OMe

OBn OMe OMe

OBn OMe OMe OMe

HO O

OMe

OMe B

OH O O

BnO

OMe H

OMe

O O

OMe

-2H+

OMe

+H+ Me C

O O

OMe

OH O O

BnO

Me OMe

BnO

IC IA L

OBn

Takemura, I.; Imura, K.; Matsumoto, T.; Suzuki, K. Org. Lett. 2004, 6, 2503.

A: 4e Electrocyclic reaction. B: 6e Electrocyclic reaction. C: Aromatization.

KÈ

H O

C009

ẠY

CF3 N

-H+ +H+

F3C

F3C F

CF3 N

Me O

+H+

O HO2C CF3 Ph NH

C Ph

OH Burger, K.; Gaa, K.; Geith, K.; Schierlinger, C. Synthesis 1989, 850.

A: ipso-Substitution of the electron-deficient oxazole. B: Claisen rearrangement. C: H ydrolysis of the azlactone.

C010 Ph Pd I

A Ph

I H Pd

H Ph

Pd I

LnPd

-HI

Pd H I

IC IA L

Pd(0)

I Pd

Larock, R. C.; Tian, Q. J. Org. Chem. 2001, 66, 7372.

A: Oxidative addition followed by carbopalladation to an alkyne. B: Oxidative addition to the aromatic C-H bond. C: Reductive elimination. D: Oxidative addition to another aromatic C-H bond.

Reductive elimination to form the C-C bond.

MeO2C

C011

CO2Me

ẠY

KÈ

MeO2C

H MeO2C C

Grissom, J. W.; Calkins, T. L.; Egan, M. J. Am. Chem. Soc. 1993, 115, 11744. Masamune-Bergman cyclization. A: Radical cyclization of an endiyne. B: Kinetically favored 5-exotrig radical cyclization. C: Abstraction of a hydrogen atom from 1,4-cyclohexadiene.

C012 N

N H

-AcOH O

Et Me O

IC IA L

N H

OAc

N H OAc

O N

B O

N H

Harley-Mason, J.; Atta-ur-Rahman Tetrahedron 1980, 36, 1057. A: Formation of a mixed anhydride. B: Acylation of the tertiary amine followed by cleavage of the C-N

bond assisted by the nitrogen lone pair of the indole.

C013 O

OH O

OMEM

t-BuOOH VO(acac)2

R OH

Me Me

O -H+

-H+

KÈ

+H+ C

OMEM

ẠY

O Me Me

MEMO

O Me Me

HO H

H H

OHC

-H+

MEMO

O Me Me

+H+

MEMO

OH H MeMe

Richter, E; Maichle-Mossmer, C.; Maier, M E. Synlett. 2002, 1097. Achmatowicz reaction (A-C).

A: Epoxidation directed by the h ydroxy group.

B: Cleavage of

theepoxide followed by the ring opening to form a cis-enal. C: C yclization to form a lactol. D: Intramolecular Diels-Alder reaction.

C014

N O

N O n-Bu O

O O

n-Bu B

n-Bu H

OH N O

n-Bu

pyridine

n-Bu E

N HO

workup

n-Bu

N TsO

+H+ D

n-Bu

TsCl

-H+

N O

IC IA L

n-Bu

-HCl

n-Bu

OH2

Corey, E. J.; Arnett, J. E; Widiger, G. N. J. Am. Chem. Soc. 1975, 97, 430.

Barton reaction (A-D, ref 097). A: Photo-induced homolytic cleavage of the nitrite. B: Abstraction of a hydrogen atom via a six-membered transition state. C: Recombination of .NO with the resulting

radical. D: Tautomerization to form an oxime. E: Beckmann rearrangement ( ref A055).

C015

O N

Me H

O H

RhLn

O O

Me H

SmI2

O O

H I2Sm

Me H

O D

RhLn

O RhLn

ẠY

RhLn

KÈ

RhLn

-N2

O O H SmI2 H

SmI2 O H O

SmI2 H O

O E

+H+

F O SmI2

workup

O SmI2

IC IA L

Padwa, A.; Sandanayaka, V. P.; Curtis, E. A. J. Am. Chem. Soc. 1994, 116, 2667. A: Formation of a rhodium carbene complex.

B: Formation of a carbonyl ylide.

C: 1,3-Dipolar

cycloaddition. D: SET to form a ketyl radical. E: Homolytic cleavage of the C-O bond. F: SET.

N2 H

n-Bu

Me O

-N2

Me O

H O

KÈ

silica gel

ẠY

+H+

Me O

Me HO

Me O Me

H Me OH

Me O

N N C

Me3Si N2 O

Me3Si

C016

-H O

Walker, L. F.; Connolly, S.; Wills, M. Tetrahedron Lett., 1998, 39, 5273.

A: Peterson olefination ( ref A074) followed by elimination of N 2 to form an alkylidene carbene. B: C-H insertion.

C017 Cl3C C N

MgBr

workup

N Tr

-H+ A

N Tr

CCl3

N Tr

CCl3

DBU Cl3CCN

H OR

CCl3

N Tr

CCl3

N B

N Tr

+H+

NH2

N Tr

CCl3

-H+

+H+

HO CCl3 O

N Tr

aq HCl

N Tr

CCl3

H2O

N Tr

CCl3

Ca(OCl)2 H2O

N Tr

IC IA L

N Tr

NH2

N Tr

NH2 Cl

Commercon, A.; Ponsinet, G. Tetrahedron Lett. 1990, 31, 3871.

KÈ

A: Formation of a trichloroacetimidate followed by aza-Claisen rearrangement. B: While formation of five-membered rings is kinetically favored, acti vation by the imidazole ring directed the cycli zation to

ẠY

form a six-membered ring.

C018

MeO

H O

Et MeO

O benzene

Me OMe OH Me

R OMe OH

reflux

MeO

OMe OH

OH R

OMe

MeO

MeO OH MeO

MeO

IC IA L

MeO

OMe

B R OMe

OMe

Tatsuta, K.; Tamura, T.; Mase, T. Tetrahedron Lett. 1999, 40, 1925.

A: Restoration of the aromaticity. B: Hetero-Diels-Alder reaction.

H2N Ts +

-H

+H+

KÈ

OMe

ẠY D

Ts N

Ph OMe

Ph3P

CO2Me

Ts N

NTs

PPh3

H Ts F3B O NH

F3B

C019

PPh3

Ts N

-H+

Ts N

B Ph3P

+H HCO2Me C

Ph3P

H CO2Me

CO2Me

Xu, Z.; Lu, X. J. Org. Chem. 1998, 63, 5031. A: Conjugate addition of Ph3P to the allenyl ester to form an enolate. B: 5-endo-trig Cyclization to form an ylide. C: Proton transfer followed by elimination of Ph 3P.

C020 Me i-PrO i-PrO

+2i-PrMgCl

Ti(Oi-Pr)2

-2Oi-Pr-

H Ti(Oi-Pr)2

Me A

OEt

Ti(Oi-Pr)2 B

+H+

FeCl2

TBSO

MeOH

OAc

KÈ

TBSO

NaOAc

U Q

O FeCl2

TBSO

Ti(OR)3 FeCl3

TBSO

Ơ H

workup

Ti(Oi-Pr)2

TBSO

OTi(OR)3

TBSO

OEt Ti(Oi-Pr)2

TBSO

Ti(Oi-Pr)2

TBSO

OEt O

TBSO

Ti(Oi-Pr)2

Me CO2Et

IC IA L

Me -

TBSO

ẠY

Hanazawa, T.; Okamoto, S.; Sato, F. Tetrahedron Lett. 2001, 42, 5455.

A: Formation of a titanium-propylene complex or a titanacyclopropane derivative ( ref B128). B:

Olefin exchange. C: Intramolecular insertion of the carbonyl group to the titanium complex.

Formation of a cyclopropane. E: Oxidative cleavage of the cyclopropane ring.

C021 B

H Cl

Cl A

Ph O

IC IA L

n-Bu Ph

workup O

Danheiser, R. L.; Martinez-Davila, C.; Morin, J. M., Jr. J. Org. Chem. 1980, 45, 1340. -Elimination to form a carbene. B: Cyclopropanation. C

anion.

-Elimination to form a cyclopropanol

D: Anion-accelerated vinylcyclopropane rearrangement (homolytic cleavage followed by

recombination of the diradical).

C022

-H2O A

U O P(OPh)2

M KÈ

O N N P(OPh)2 N N

-N2

O N P(OPh)2 N

KOH

ẠY

N N N

O P(OPh)2

O N P(OPh)2 N N N

N H

Hamada, Y.; Shioiri, T. Org. Synth., Coll. Vol.

CO2H

1990, 207

A: Formation of an enamine. B: 1,3-Dipolar cycloaddition. C: Cleavage of the N-N bond.

Tiffeneau-Demjanov-type ring contraction.

C023 TMS

TMS I O

H O

TMS Me

O B

TMS

IC IA L

Me Ac2O

TMS

workup

CH3 O

Li O

TMS

O Me

O H

-CO2 Me

Q H OAc E

KÈ

AcO O

TMS

H SiMe 3 N

O N

Nayyar, N. K.; Hutchison, D. R.; Martinelli, M. J. J. Org. Chem. 1997, 62, 982.

ẠY

A: Demethylation via an SN2 process. B: Cycli zation of the mixed anhydride followed by formation of a E: Protodesilylation.

1,3-dipole. C: Intramolecular 1,3-dipolar cycloaddition. D: Decarboxylation.

C024 Me

Me O

OH PhSe Br

-H+ O

PhSe

Me O

O PhSe

NaIO4 Me O

toluene

reflux C

O H

O Petrzilka, M. Heir. Chim. Acta 1978, 61, 3075.

A: Selenation of the electron-rich enol ether. B: Intramolecular acetal formation. C

IC IA L

the selenoxide. D: Claisen rearrangement.

OMe

OMe OBn

O AcO

HgCl

ClHg AcO

BnO

OMe OBn O

AcO

+H+ B

BnO

OBn

OH OBn

Chida, N.; Ohtsuka, M.; Nakazawa, K.; Ogawa, S. J. Chem. Soc., Chem. Commun. 1989, 436.

OBn

+H+

HgCl

OBn

-H+

BnO

AcO

BnO

HgCl

AcO

H2O

C025 Cl Hg Cl

-Elimination of

Ferrier rearrangement. A: Oxymercuration of enol ether. B: Intramolecular aldol reaction of the

mercury enolate with the aldehyde.

KÈ

C026

ẠY

O Me

Oi-Pr

O Me Ph

i-Pr O H i-Pr

OLi O A

O Li O

i-Pr

Ph Me

O i-Pr Me

OH O

workup +H+

Ph Me

i-Pr Me Me

O i-Pr Me

OH O

NaOH Ph

MeOH

OH OH Me

OH OH

workup +H+

Ph Me

Mascarenhas, C. M.; Duffe y, M. O.; Liu, S.-Y.; Morken, J. P. Org. Lett. 1999, 1, 1427. A: Intramolecular hydride transfer (Cannizzaro-type reaction) through a

IC IA L

Tishchenko reaction.

chair-like transition state.

C027

F3B

-H O

H OH

KÈ

-H2O

ẠY

H2O

HO OH OH Me

OH2

B Me

-H+

+H+

-H

F3B H O H

-H+

F3B H

+H+

F3B

BF3

O Me

Nagumo, S.; Suemune, H.; Sakai, K. J. Chem. Soc., Chem. Commun. 1990, 1778. A: Intramolecular acid-catalyzed aldol reaction. B: Grob-type fragmentation.

C028 O hv

Me3Sn SnMe3

Me3Sn

OH O

IC IA L

N Et HO

Et HO

N Et HO

Et HO

R I

O N

-HI

Et HO

Curran, D. P.; Ko, S.-B.; Josien, H. Angew. Chem. Int. Ed. 1995, 34, 2683.

KÈ

A: Radical addition of an isocyanide to form an imidoyl radical. B: Atom transfer reaction.

ẠY

C029

Me Me O

MeO

O Ar

A NMe

N Me

Me Me

O Ar

O B

N Me

Me Me O

Me Me Me

N Me

NMe

AlCl2 Me

B Me

Me AlCl2 O

H O -H+

NMe

workup

MeO

NMe

t-BuOK

MeO

OMs Et3N MsCl

MeO

NaBH4

MeO

NMe

OMs NMe

Me H

N Y MeO

O Me

NMe Me

MeO

NMe

t-BuO

OMs

MeO

IC IA L

AlCl2Me

AlCl2 O

KÈ

Fuchs, J. R.; Funk, R. L. Org. Lett., 2001, 3, 3923.

A: Acylation of the imine to form an enamide. B

-amidoacrolein. C:

ẠY

Intramolecular conjugate addition of the electron-rich aromatic ring to the amidoacrolein.

C030

H H BH Me

CH3CHO

H B

A Me

B O H

H Me

Me -

B OEt

B OEt H Cl O Me

Cl OMe

IC IA L

Cl Cl OMe

B H OEt Cl O Me

OEt -MeOH H B Cl -EtOH MeO H

O B OH

H Cl

OOH

OOH OH

O OH H B Cl HO OH

OH H Cl B HO

NaOAc aq H2O2

OMe

B H EtO

Cl Cl t-BuO

Brown, H. C.; Mahindroo, V. K.; Dhokte, U. P. J. Org. Chem. 1996, 61, 1906. B: H ydride transfer via a six-membered

A: Sequential hydroboration to form a trialkylborane.

transition state. See Meerwein-Ponndorf-Verley reduction ( ref B002).

Me Me Me

C031

N C N H O

KÈ

HN Me

N Ph Me

HN O

Me Ph

O N

O H Ph

O Ph

ẠY

O Ph

O Ph C

Ph D

E Ph

Sponholtz III, W. R.; Trujillo, H. A.; Gribble, G. W. Tetrahedron Lett. 2000, 41, 1687. A: Acti vation of the carboxyl group as an O-acylisourea. B: Generation of a 1,3-dipole. C: 1,3-Dipolar cycloaddition. D: Decarboxylation to form a 1,3-dipole. E: Intramolecular 1,3-dipolar cycloaddition.

C032 O

-H+

+H+

Me H O

OH Me

IC IA L

Fukuyama, T.; Li, T.; Peng, G. Tetrahedron Lett. 1994, 35, 2145. Abnormal Claisen rearrangement.

A: Claisen rearrangement followed by tautomerization.

Intramolecular oxy-ene reaction to form a cyclopropane. C: Retro oxy-ene reaction.

H n-Bu

n-BuLi RCHO

O S

PhS Cl

O S

KÈ

O S

ẠY D

S Ph

O S

Ph H R

aq NH4Cl

O S

C033

O R S Ph

OH R Schreiber, S. L.; Satake, K. J. Am. Chem. Soc. 1984, 106, 4186.

A: Formation of a sulfenate. B: [2,3] Sigmatropic rearrangement. C: Deprotonation followed by addition to the aldehyde (pKa D MSO = 35).

D: [2,3] Sigmatropic rearrangement of the sulfoxide. E:

[2,3] sigmatropic rearrangement of the sulfenate.

C034 OTBS

OTBS

RuLn

OTBS RuLn

RuLn

R Me

OTBS

RuLn

OTBS

RuLn

OTBS

LnRu

OTBS

LnRu

RuLn

Ru Ln

IC IA L

OTBS

C Me

KÈ

Ru Ln

RuLn

OTBS

Zuercher, W. J.; Scholl, M.; Grubbs, R. H. J. Org. Chem. 1998, 63, 4291.

Domino intramolecular enyne metathesis. A: Alkene metathesis at the terminal olefin. B: Sequential intramolecular alkyne metathesis to form a kinetically favored, six-membered intermediates.

ẠY

Intramolecular alkene metathesis.

C035

OBoc

OBoc O

O Ph

Ot-Bu

A Ph

O O

Ot-Bu

OBoc

B Ph

C Ph

OEt

Jones, R. M.; Selenski, C.; Pettus, T. R. R. J. Org. Chem. 2002, 67, 6911

IC IA L

A: Intramolecular acyl transfer (pKa PhOH = 10, t-BuOH = 19). B: Generation of o-quinonemethide C: Hetero-Diels-Alder reaction to form an endo-adduct.

C036 N Br

OBn O

HO Me

OBn

-H+

BnO BnO

OBn

BnO BnO

OBn

BnO BnO

OBn

BnO BnO

OBn

BnO BnO

OMe

Fraser-Reid, B.; Konradsson, P.; Mootoo, D. R.; Udodong, U.

J. Chem. Soc., Chem. Commun. 1988, 823.

A: Bromination of the olefin causes the formation of a five-membered oxonium ion.

C037

ẠY

Me Me

SMe Me

Me Me

Cl Hg Me Cl

Me Me ClHg

OH2

Me Me

Me HS OH Me

-H+

+H+

Me Me HgCl

Me Me Me HgCl

C Me Me

-H+

Me Me

S Me

HgCl2

KÈ

Me Cl Me

Me Me

Michelot, D.; Linstrumelle, G.; Julia, S. J. Chem. Soc., Chem. Commun. 1974, 3, 10. A: Generation of an alkylidene carbene. B: Formation of a sulfur ylide (carbene is electrophilic). C:

C038 O OMe

CO2Me

OMe

OH -H2O

CO2Me

CO2Me N

MeO

-N2

CO2Me

CO2Me N3

H OMe

IC IA L

[2,3] Sigmatropic rearrangement.

NH2

N H

CO2Me

ẠY

KÈ

N H

CO2Me

CO2Me Knittel, D. Synthesis 1985, 186.

A: Claisen-Schmidt reaction. B: Formation of an azirine. C: Cleavage of the azirine ring to form

either 1) a nitrene which undergoes C-H insertion or 2) a diradical that recombines to form, upon aromatization.an indole.

C039 OLi OLi

OLi workup Me

+H+

OH2

-H+

Me +H+

OMe

Me Me H

OMe

Me OMe H

-H+

A Me Me

H3O+

Me Me

Me H

OMe

-H+

Me MeOH

MeOH OH2

OH H SO 2 4

IC IA L

Hiyama, T.; Shinoda, M.; Nozaki, H. J. Am. Chem. Soc. 1979, 101, 1599.

A: Nazarov reaction ( ref B026).

Ph I O OCOCF3 OMe

OCOCF3 I Ph OCOCF3

C040

OMe

KÈ

ẠY

-H

OMe

OMe O

Me Me

Me Me O

mesitylene 200oC

Me Me

OMe O

O C

Me Me

OMe O

Me Me H O e OM O

Hsiu, P.-Y.; Liao, C.-C. J. Chem. Soc., Chem. Commun. 1997, 1085. A: Oxidation of the phenol to form a mixed o-quinone monoacetal. B: Intramolecular Diels-Alder

reaction. C: Cope rearrangement.

C041 MeO N

MeO

MeO N

MeO

IC IA L

MeO

H OMe

MeO N

MeO

O H

MeO

O H

MeO

Naito, T.; Tada, Y.; Nishiguchi, Y.; Ninomiya, I. Heterocycles 1981, 16, 1137.

A: 6e Electrocyclic reaction. B: Reduction of the acyliminium ion from the convex face.

C042 O

Y U

TBS

R A R TMS

KÈ

R C TMS

TBSO

ẠY

TMS

O u e t B M 2Si

TBSO

workup

R TMS

O TBSO

TBSO

+H+

D TMS

TMS

Takeda, K.; Takeda, M.; Nakajima, A.; Yoshii, E. J. Am. Chem. Soc. 1995, 117, 6400. A: 1,2-Addition of the enolate to the acylsilane. B: Brook rearrangement. C: Cyclopropanation. D: Anion-accelerated divinylcyctopropane rearrangement.

C043

Me H

SmI2

I2SmO Me

SmI2

I2SmO Me

C O

I2SmO Me

HO Me

workup

+H+

D H

SmI2

IC IA L

SmI2 O

Chem. Commun. 1998, 1875.

B: 5-exo-trig Radical cyclization to form a radical at a cyclopropylcarbinyl position which

A: SET.

Boffey, R. J.; Santagostino, M.; Whittingham, W. G.; Kilburn, J. D.

induces cleavage of the cyclopropane ring (cf. radical clock). C: 5-exo-dig Radical cyclization. D:

SET.

C044

Me O

OMe

KÈ

H2N

Me O

NH2

+H+

OTs H

ẠY

MeO

Me Me H

NH2

Me NH

-H+ O

Me Me

+H+ B

NH2

O NH2

Me Me

H2O

Me Me O

IC IA L

Me OH

-H

H O

+H+

-H+

H -CO2

O C

MeO

Tietze, L. F.; WöIfling, J.; Schneider, G. Chem. Ber. 1991, 124, 591. A: Grob-type fragmentation. B: Knoevenagel reaction ( ref A018). C: Intramolecular hetero-Diels-

Alder reaction. D: Retro Diels-Alder reaction to generate a highly reactive acylketene.

C045

OEt

Br Br

O O

OEt

t-Bu

Me CO2Et

t-Bu

Me O

CO2Et

Me O

KÈ

ẠY

OEt

Me O

-CO2

Me Me

workup

+H+ O

O Me O

EtO Me

Shindo, M.; Sato, Y.; Shishido, K. J. Org. Chem. 2001, 66, 7818. A: Formation of an ynolate. B: Addition of the ynolate to the ketone leads to the formation of a strained -lactone enolate. C: Claisen condensation followed by aromatization with decarboxylation.

C046

CO2Me

OMe

O N N

CO2Me

-N2

O -

O MeO

H B

OMe

C O

OMe

MeO2C

MeO

OMe

IC IA L

Spino, C.; Rezaei, H.; Dupont-Gaudet, K.; Belanger, F. J. Am. Chem. Soc. 2004, 126, 9926.

A: Fragmentation to form a dialkoxycarbene. B: Cyclopropanation. C: Cleavage of the cyclopropane

ring.

C047

MeO

O MeO

KÈ

N H

MeO

Ph N

Me Br

ẠY

MeO

MeO mCPBA

LiAlH4 AlCl3

O N

N Ph

MeO

MeO +

-H

Ph MeO

-H

+H+

Me OH

N Ph

MeO N

Me OH

KCN

O H

IC IA L

MeO +

MeO

+H+

Makisumi, Y.; Takada, S. Chem. Pharm. Bull. 1976, 24, 770.

A: [2,3] Sigmatropic rearrangement of the N-oxide. B: [3,3] Sigmatropic rearrangement.

C048 O S N CO2Me

ẠY

KÈ

CO2Me workup S O Ph

PhMgBr

CO2Me

S O

Ph NHCO2Me

HMPT EtOH 80oC

H N

NHCO2Me D O SPh

S O

Ph S O

CO2Me

Ph S O

NHCO2Me

H NH

OMe

P(NMe2)3 Anderson, G. T.; Chase, C. E.; Koh, Y-H.; Seien, D.; Weinreb, S. M. J. Org. Chem. 1998, 63, 7594.

A: Hetero-Diels-Alder reaction. B: Cleavage of the S-N bond by SN2 attack of Ph MgBr.

C: [2,3]

Sigmatropic rearrangement (reversible process). D: Irreversible cleavage of the S-O bond by attack of a thiophile (P(NMe2)3) generates an alkoxide ion which then cyclizes to give an oxazolidinone.

C049 Me t-Bu Si Cl Me

Me B

Me O

O O OTBS Me

B Me

O O

Me Me OH

H Me Me

H2 Pd/C

O O

O O OTBS

OTBS

Me Me OH

IC IA L

Casey, M.; Culshaw, A. J. Synlett

A: Formation of a silyl enol ether. B: 1,3-Dipolar cycloaddition of O3 followed by cleavage of the ozonide to form a 1,3-dipole (carbonyl oxide). C: 1,3-Dipolar cycloaddition. D: Reductive cleavage of

the O-O bond.

C050

KÈ

Ar Et

CN O

ẠY Ar

O N R

N C N H R

PPh3

NHEt

PPh3 H

CN NHEt

O3 O

PPh3 CN

Ph3 P O NC O O

Br Br

OMe

O O H2N

N H

IC IA L

OMe

Wasserman, H. H.; Wang, J. J. Org. Chem. 1998, 63, 5581. A: Acti vation of the carboxylic acid as an O-acylisourea. B: Acylation of the stabilized ylide. C: 1,3-

Dipolar cycloaddition of O3 to the ylide. D: Fragmentation to generate an acyl cyanide.

C051 Me

-H+

OH O

CO2Et

ẠY D

-H+

CO2Et

Ơ OH

O NH O CO2Et

+H+

CO2Et

OH2

CO2Et

TMSCH2MgCl CeCl3

OEt

C O

OEt

Cl2Ce CH2SiMe3

OEt

N Pr

KÈ

EtOH B

HOEt

-AcOH

NaBH4 H2SO4

NH O CO2Et

+H+

NH2

SiMe3

Cl2Ce CH2SiMe3

OEt

SiMe3 O

Pr SiMe3

OEt SiMe3

aq HCl O N + +H Pr C

H OEt

O SiMe3

N SiMe3

D Pr

Chalard, E; Remuson, R.; Gelas-Mialhe Y.; Gramain J.-C.; Canet I. Tetrahedron Lett. 1999, 40, 1661.

IC IA L

A: Formation of a succinimide via a mixed anhydride. B: Partial reduction of the imide. C: Peterson

olefination ( ref A074) to form an allylsilane. D: Intramolecular addition of the allylsilane to the

acyliminium ion.

C052 CO2H (COCl)2

O Cl

Et3N

Me OH

Me O

MeLi

Cu(OAc)2 Mn(OAc)3

Mn(OAc)2

Cu(OAc)2

Me O

CuOAc O

KÈ

ẠY

Snider, B. B.; Vo, N. H.; Foxman, B. M. J. Org. Chem. 1993, 58, 7228.

A: Formation of a ketene. B: Intramolecular [2+2] cycloaddition. C: Generation of an oxygen radical.

D: Cleavage of the cyclobutane ring to form a stable tertiary carbon radical. E: 5-e xo-trig Radical cyclization followed by oxidation with Cu(OAc)2.

C053 Me3Si Me3Si OTf

H O SiMe3

H -H+

O Ph

+H+

O Ph SiMe3

IC IA L

Ph SiMe3

Si Me Me Me

Roush, W. R.; Dilley, G. J. Synlett. 2001, 955

Intramolecular Hosomi-Sakurai-type reaction.

O O

KÈ N2

ẠY

Li Br n-Bu

i-Pr3SiCl

H Br

n-Bu

C054

i-Pr3SiO OSii-Pr3

hv O

O O

O C

i-Pr3SiO

O O

O i-Pr3SiO

D OSiPr3

OSii-Pr3 C

OSii-Pr3

-H+ OSii-Pr3

+H+ E

OSii-Pr3

Danheiser, R. L.; Trova, M. P. Synlett. 1995, 573.

-elimination followed by insertion of the carbene into the C-

C bond (Kowalski reaction).

B: Wolff rearrangement.

C: [2+2] Ketene cycloaddition.

D: 4e

Electrocyclic reaction. E: 6e Electrocyclic reaction followed by aromatization.

C055

Ts N

OTf Ts Me

I Ph

Ts N

Ph Ts Me N

Ts N

IC IA L

H N

n-Bu

Feldman, K. S.; Mareska, D. A. J. Org. Chem. 1999, 64, 5650. A: Addition of a sulfonamide ion to the electron-deficient acetylene to form an alkylidene carbene. B:

Cyclopropanation. C: Homolytic cleavage of the strained cyclopropylidene ring.

C056 H

NH3

KÈ

OBn

ẠY

OHC

OBn H

H OH

OBn

N OH

OBn H

-H2O N

OBn

OBn NH4OAc AcOH 75oC

OBn

H H A

H B

-H+

IC IA L

Heathcock, C. H.; Stafford, J. A. J. Org. Chem. 1992, 57, 2566. A: Aza-Diels-Alder reaction. B: Cation-olefin cyclization.

H2 Lindlar catalyst A HO

C057

H H OH

Nicolaou, K. C.; Petasis, N. A.; Zipkin, R. E.; Uenishi, J.

J. Am. Chem. Soc. 1982, 104, 5555.

A: Partial reduction of the alkynes to form a tetraene. B: 8e Conrotatory electrocyclic reaction. C: 6e

Disrotatory electrocyclic reaction.

KÈ

C058

ẠY

Cl Cl

O A Cl O

Cl O

Tol

N(Boc)2

Cl H Cl R

O o S T l O

Cl H Cl B R

O o S T l O

Cl O

Me C

O STol N(Boc)2

Marino, J. P.; Rubio, M. B.; Cao, G.; de Dios, A. J. Am. Chem. Soc. 2002, 124, 13398. A: Generation of dichloroketene.

B: [3,3] Sigmatropic rearrangement.

C: Cyclization of the

carboxylate to the sulfenium ion.

C059

IC IA L

O Me

Cl3Al Cl

O S Me Me

MeO

MeO A

N R

MeO

Me Me

N R

MeO

Cl3Al Cl S

Chung, J. Y. L.; Reamer, R. A.; Reider, P. J. Tetrahedron Lett. 1992, 33, 4717.

A: FriedeI-Crafts acylation at the indole 3-position. B: Cleavage of the strained four-membered ring by

chloride ion. C: Intramolecular electrophilic substitution by the resulting sulfenyl chloride.

KÈ

C060

A C

PdLn

OMe H

PdLn

ẠY

O Me C PdLn

Me OH

O OMe

-H+ +H+ B

O OMe

O Me

C PdLn

OMe PdLn

-Pd(0)Ln

OMe

Minami, I.; Yuhara, M.; Tsuji, J. Tetrahedron Lett. 1987, 28, 629.

IC IA L

A: Formation of an allenylpalladium species. B: Addition of the acetoacetate anion to generate a -allylpalladium complex. C

-allylpalladium complex.

C061 Me

Br LnPd

Br PdLn B

Br O

Br LnPd Me

Pd(0)Ln

PdLn Br C

H PdLn Br

BrMe LnPd

Me yer, R E.; Parsons, P. J.; de Meijere, A. J. Org. Chem. 1991, 56, 6487.

A: Oxidative addition. B: Sequential intramolecular carbopalladation. C

KÈ

C062 O

H O

ẠY

+H+

-H+ SiMe3

O Me3Si

OH2 O

+H+

SiMe3

-Elimination.

Me3Si

decalin 170oC A

H O Me3Si

Me3Si

Me3Si EtAlCl2

Me3Si O

O Cl2EtAl

Me3 Si Cl - e M 3SiCl

O B

workup

+H+ H OAlEtCl

H OAlEtCl

IC IA L

AlEtCl2

H OH

Paquette, L. A.; Ladouceur, G. J. Org. Chem. 1989, 54, 4278.

A: Claisen rearrangement via a boat-like transition state. B: Intramolecular Hosomi-Sakurai reaction.

O H

O Me

U B

Ph Br

OMe OH

KÈ

BrZn Zn

ẠY D

-H

BzO Me

Br N

OMe OH

O Me O Br

OMe OH

O Me

O C

OMe OH

ZnX O

O OH

BzO Me

OZnX O

OMe OH

O Me

ZnX2

BzO Me

O Me

N Br

OMe OH

C063

BzO Me

OH workup +

BzO Me

Holt, D. J.; Barker, W. D.; Jenkins, P. R. J. Org. Chem. 2000, 65, 482. A: Radical bromination of the benzylic position. B: Formation of a stable carbocation. C: SN2 reaction. D: 1,2-Alkyl shift.

C064

A N NTs H

N N Ts

N N

IC IA L

n-Bu

C H

Bian, N.; Jones, M., Jr. Tetrahedron Lett., 1993, 25, 3967. A: Formation of a diazoalka

-elimination. B: Elimination of N 2 to form a carbene. C: Insertion

of the carbene to the C-C bond. D: Retro Diels-Alder reaction.

C065 NH2 Ns N H

SiMe3

TBSO

CO2Et N N EtO2C PPh3

SiMe3 -H+

PPh3

CO2Et N NH EtO2C

KÈ

ẠY D

Ph3P

SiMe3

HN H

SiMe3 TBSO

O S O O2N

SiMe3

-N2 C

TBSO

+H+

TBSO

Ns N NH2

TBSO

H Myers, A. G.; Zheng, B. J. Am. Chem. Soc. 1996, 118, 4492.

A: Mitsunobu reaction ( ref A045). B: Elimination of a sulfinic acid. C: Sigmatropic elimination of N2 (stereospecific delivery of a hydride via a concerted mechanism).

C066 BrMg O A Me

MgBr

N O

BrMg H

H O N MgBr

OMgBr

O N MgBr

IC IA L

N O

BrMg H

workup +H+

N MgBr

N Me

N H

Bosco, M.; Dalpozzo, R.; Bartoli, G.; Palmieri, G.; Petrini, M. J. Chem. Soc., Perkin Trans. 2 1991, 657.

Bartoli indole synthesis. A: Reduction of the nitro group by means of addition of CH 2=CHMgBr and elimination of an enolate to form a nitroso compound. B: Addition of CH2=CHMgBr to the nitroso

group. C: [3,3] Sigmatropic rearrangement.

KÈ

Cl4Ti

C067

ẠY

Cl4Ti

O O C

Me N

TiCl4 B

TiCl4

O Me

N O

TiCl4 N

O N

O Me

Yoon, T. P.; Dong, V. M.; MacMillan, D. W. C. J. Am. Chem. Soc. 1999, 121, 9726. A: Formation of a ketene. B: Aza-Claisen rearrangement through a chair-like transition state.

C068 S

S TBSO

Cl O A

S HO

IC IA L O

O HO

+H+ B

-H+

O H

workup

-H+

+H+

H t-Bu O Si O e e M M F

CSA

Cl Cl

AcOH

TBSO

Vedejs, E.; Buchanan, R. A. J. Org. Chem. 1984, 49, 1840.

A: [3,3] Sigmatropic rearrangement. B: Intramolecular acyl transfer reaction.

(OC)4Cr

N Bn

O A (CO)4Cr OMe

ẠY

KÈ

(OC)4Cr C O

OMe

C069

N Bn O

I2 N Bn O

OMe

N Bn O

H Me OMe

H I

N C Ph

Me OMe

N Bn O

H Me OMe

Me OMe

H I

N O

Me OMe

I eur, C. J.; Miller, M. W.; Hegedus, L. S. J. Org. Chem. 1996, 61, 2871. A: Photo-induced insertion of CO to form a ketene. B: Aza-Claisen rearrangement. C: Intramolecular

iodoamidation followed by debenzylation in an SN2 fashion.

C070 OH OH R Me Me

O O

-H

OH Me Me

O Me

+H+ B

IC IA L

O O

O OH

-H

OH +H+ Me Me C

H OMe

NaOMe

O Me

OH e O MeM

Me Me

Schreiber, S. L.; Sammakia, T.; Uehling, D. E. J. Org. Chem., 1989, 54, 15.

A: Activation by cyclization. B: Formation of an orthoester followed by cleavage of the five-membered

lactone. C: Intramolecular interception of the stable carbocation by the secondary alcohol.

Cleavage of the resulting orthoester. E: SN2 reaction at the less hindered carbon with chloride ion.

KÈ

C071

F3B

N H

-H

NHBn N H

ẠY

N H

CO2Me

NBn

BF3

R CO2Me

NBn -H+ H

A N H

R CO2Me

N H

R CO2Me

NBn

NBn H

R CO2Me

N H NBn

NBn

-H+

R CO2Me

N H

CO2Me

N H

R CO2Me

N H

IC IA L

R CO2Me

N H

Parsons R. L.; Berk J. D.; Kuehne M. E. J. Org. Chem. 1993, 58, 7482.

A: Mannich reaction followed by [3,3] sigmatropic rearrangement. B: Mannich reaction.

C072

N OH

O O

mCPBA

MeOH

N OH

O H

N O

O Me

H2, Pd/C

KÈ

NaH

N H

N Me O'Neil, I. A.; Cleator, E.; Ramos, V. E.; Chorlton, A. P.; Tapolczay, D. J.

ẠY

Tetrahedron Lett. 2004, 45, 3655.

A: Cope elimination. B: Retro Cope elimination.

C073 O

TMS

TMS H OR

O H

TMS

O A

O TMS B H

F H

workup

+H+

OTMS

O SiMe3

TBAF

IC IA L

H SiMe3

Ovaska, T. V.; Roses, J. B. Org. Lett. 2000, 2, 2361. A: 5-exo-dig Cyclization of the alkoxide ion. B: Claisen rearrangement. C: Migration of the silyl group

to form a silyl enol ether.

N H

C074

Q M

Rh2(OAc)4

RhLn S

ẠY

RhLn N

O RhLn

D D

RhLn N N

N B

H OH

KÈ

SH O

O N

Raney Ni E

O N

Fang, F. G.; Prato, M.; Kim, G.; Danishefsky, S. J. Tetrahedron Lett. 1989, 30, 3625. A: Conjugate addition of a thiolactam anion. B: Formation of a rhodium carbene complex. C: Attack of the sulfur atom to the rhodium carbene complex followed by formation of a thiirane. D: Cleavage of

the thiirane assisted by the nitrogen lone pair. E: Desulfurization.

C075 O O

OMe N N

RhLn

O Me

OH O Me

MeO

OMe

F3B

Me O

MeO

Me O Me OH

BF3

Me H HO

O Me O

MeO

Me O

F2B

BF3-Et2O

O Me OH

HO Me

-H+

OMe

MeO

RhLn

OMe

OMe N RhLn N

+H+ OMe

Me LnRh

IC IA L

Drutu, I.; Krygowski, E. S.; Wood, J. L. J. Org. Chem. 2001, 66, 7025.

A: Formation of a rhodium carbene complex. B: Addition of an alcohol to the carbene complex. C: Formation of an (Z)-enol. D: [3,3] Sigmatropic rearrangement via a chair-like transition state. E: 1,2-

KÈ

Migration through a synperiplanar transition state.

ẠY

C076

F3B O O

F3B O

Me O

SnMe3 SnMe3

SnMe3

workup +H+

AcO Me

H O

Pb(OAc)4

OAc Pb O AcO O

OAc O

SnMe3

AcO

-H

+H+ B

SnMe3

-H+

AcO

OAc Pb

(Ph3P)3RhCl

O Me

SnMe3

IC IA L

H O

Posner, G. H.; Wang, Q.; Halford, B. A.; Elias, J. S.; Maxwell, J. P. Tetrahedron Lett. 2000, 41, 9655.

A: Attack to the epoxide takes place from the less hindered side to form the trans-product. B:

Formation of a hemiacetal. C: Oxidative fragmentation induced by Pb(OAc)4.

n-Bu

O A

C077

Me H

workup

KÈ

+H+ Me

Sayo, N.; Kimura, Y.; Nakai, T. Tetrahedron Lett. 1982, 23, 3931.

A: [2,3] Wittig rearrangement. B: Oxy-Cope rearrangement.

ẠY

C078

CHO

-H2O

C6H11 N R

O Me

A O Me

Et3N AcCl

C6H11 N AcO H

O O Me

C6H11 N

-H+

C6H11 N

OAc R

NaOAc OHC OAc aq AcOH R

O Me

IC IA L

Vosburg, D. A.; Weiler, S.; Sorensen, E. J. Angew. Chem. Int. Ed. 1999, 38, 971. A: Formation of a nitrone. B: Acetylation followed by [3,3] sigmatropic rearrangement.

OTBS Me

B SMe2

O O OTBS Me

AcO

H O

DBU

O OTBS

U Q

OTBS Me

OTBS O

AcO

+H+ D

O O O SMe2

Ac2O Et3N

-H+

-DMSO

OTBS

O O O

HO O

C079

toluene 100oC

OTBS Me

E OTBS

KÈ

OTBS

ẠY

TBSO H O

OTBS O

Bauta, W. E.; Booth, J.; Bos, M. E.; DeLuca, M.; Diorazio, L.; Donohoe, T. J.; Frost, C.; Magnus, N.; Magnus, P.; Mendoza, J.; Pye, E; Tarrant, J. G.; Thom, S.; Ujjainwalla, F. Tetahedron. 1996, 52, 14081.

Achmatowicz reaction (A-D). A: Diels-Alder reaction of singlet oxygen.

B: Reductive cleavage of the

endoperoxide with Me 2S. C: Elimination of DMSO to form cis-enal. D: C yclization to form a lactol. E: Generation of a pyrylium ion (or a carbonyl ylide). F: 1,3-Dipolar cycloaddition.

C080 H

O hv

Cl A O

C O

O -CO D O

O -CO

E O

IC IA L

Et3N

1973, 297

Turro, N. J.; Leermakers, P. A. Vesley, G. E Org. Synth., Coll. Vol

A: Formation of a ketene. B: [2+2] Head-to-tail dimerization of a hindered ketene. C: Norrish type I

cleavage of the ketone followed by decarbonylation to form a diradical. D: Recombination of the

diradical.

C081 TiCl4 Me

KÈ ẠY D

Me SiMe3 C

TiCl4

Me Me

SiMe3 Me

Danheiser, R. L.; Fink, D. M.; Tsai, Y.-M. Org. Synth., Coll. Vol.

1993, 347.

Danheiser annulation. A: Conjugate addition of the allenylsilane to form a carbocation stabilized by the silicon atom.

C082

Et O

Et O H Ph

Ph2P Cl

n-Bu

Et O PPh2 Ph

Me O

Me O Ph2P Et O

Ph2P Et O

O Me

Me O

O O PPh2

O Et Ph

O Ph

H O

IC IA L

Mukaiyama, T.; Shintou, T.; Fukumoto, K. J. Am. Chem. Soc. 2003, 125, 10538.

A: Formation of a phosphinite ester. B: Addition of the phosphinite to the electron-deficient quinone.

C: SN2 reaction with inversion of configuration.

C083

OMe

KÈ

MeO

ẠY

BnO

OMe MeO

Cl H

A TMS N TMS

BnO

OMe

MeO

MeO B H

BnO

Ph3P C

OMe

MeO

TsOH

Me MeO

-H2O D

BnO

IC IA L

Taber, D. E; Neubert, T. D. J. Org. Chem. 2001, 66, 143.

-Elimination to form an alkylidene carbene. B: C-H insertion at the kinetically favored position. C:

C084

N Ns Bn N C

N Ns

H N

Ozonolysis. D: Intramolecular aldol reaction.

N Ns

ẠY

N Ns

N Bn

N Bn O

NHBn

-H+

-H

N Bn

+H+

NHBn

-H+ N Bn

NsHN

+H+

N Bn NsHN

O Paulvannan, K. J. Org. Chem. 2004, 69, 1207

A: Ugi reaction ( ref C007). B: Intramolecular Dielsrelease the ring strain.

NHNs

NHBn N Bn

KÈ

O Ns H N

+H+

N Ns N Bn

-H+

BnHN

Bn NH O

-elimination to

C085 Me Me

Me Me

workup

Me Me HO

+H+

Me Me HO Cl S O Cl

Me Me

Me A

O S Cl O

Me 60 C

Me Me Me

O Me

MeH

OHC

MgCl

Me workup

OMgCl

+H+

MgCl

MgCl Me

Mg B

SOCl2

IC IA L

MeH

Oppolzer, W.; Bättig, K. Tetrahedron Lett. 1982, 23, 4669.

A: Formation of an allyl chloride via SN2' reaction.

B: Formation of a Grignard reagent.

Magnesium-ene reaction through a chair-like conformation.

ẠY

Ph Ph

Ph Ph Ph

Ot-Bu

Ph H

KÈ

C086

OEt

Ph Ph

O OEt

Ph P B

Ph Ph

EtO C

Ph P Ph

OEt O EtO Ph

Ph P Ph EtO

O P Ph Ph Ph

Fujimoto, T.; Kodama, Y.; Yamamoto, I.; Kakehi, A. J. Org. Chem. 1997, 62, 6627.

A: Conjugate addition of an ylide.

B: Intramolecular proton transfer to generate an ylide.

Intramolecular Wittig reaction.

I PdLn

I B

NTs

PdLnI

NTs

O PdLnI B

NTs

O A

O C PdLnI

N Ts

Pd(0)

IC IA L

C087

O CO

PdLnI

NTs

PdLnI O

NTs

LnPd

KÈ

-Pd(0) E

N Ts

von Seebach, M.; Grigg, R.; de Meijere, A. Eur. J. Org. Chem. 2002, 3268.

A: Pd-mediated carbonylation to form an acylpalladium species. B: Carbopalladation to a strained -Carbon elimination. D: Intramolecular carbopalladation to the resulting strained olefin. E:

ẠY

olefin. C

Reductive elimination of the palladacycle.

C088 O

O Me SPh

Me SPh

workup +H+

Me SPh

HBF4 +H+

H H O

Me SPh

H2O

SPh

-H+ +H+

A SPh

LiBH(s-Bu)3 MeLi, KOEt

B O

H Bs-Bu3

Me workup

+H+ O

OH S Ph H

IC IA L

Danheiser, R. L.; Martinez-Davila, C.; Sard, H. Tetrahedron. 1981, 37, 3943.

A: Pinacol-type rearrangement. B: Reduction of the ketone. C: Anion-accelerated vinylcyclobutane-

cyclohexene rearrangement.

C089 Boc N

S C S

KÈ

Boc N

Boc N S H3C I

O S

SMe

SMe S

SnBu3

Boc N

Boc N O

SnBu3

Boc N NBoc

D H SnBu3

SMe

Boc N

workup

Boc N

ẠY

Bu3SnH AIBN

Boc N

Hodgson, D. M.; Maxwell, C. R.; Wisedale, R.; Matthews, I. R.; Carpenter, K. J,; Dickenson, A. H.; Wonnacott, S. J. Chem. Soc., Perkin Trans. 1 . 2001, 3150. A

-Elimination of the epoxide to form a carbene.

B: C-H insertion.

C: Barton-McCombie

deoxygenation of a xanthate ( ref A051). D: Formation of a radical at a cyclopropylcarbinyl position

IC IA L

induces cleavage of the cyclopropane ring (cf. radical clock).

C090 Me -H+

N OH2

+H+ HO

HO R

Angle, S. R.; Fevig, J. M.; Knight, S. D.; Marquis, R. W., Jr.; Overman, L. E

J. Am. Chem. Soc. 1993, 115, 3966

KÈ

A: Aza-Cope rearrangement. B: Mannich reaction.

C091

ẠY

Cl3Sn Cl

Cl3SnO

O RO A

Me Ph

Cl3SnO

O NaHCO3

Me Ph

workup

benzene reflux

OR A

N O O Me

NiCl2 NaBH4

H Ph

H2N Me

-ROH

O H

O workup

H H2N Me

H2N Me

+H+

IC IA L

H2N Me

Denmark, S. E.; Dixon, J. A. J. Org. Chem. 1998, 63, 6178. A: In verse electron demand hetero-Diels-Alder reaction. B: 1,3-Dipolar cycloaddition. C: Reductive

cleavage of the N-O bonds.

BnO

Et3N

S N

BF3-Et2O

H2O

KÈ

S N

OH2

-SO2

BnO

C092

S O BF3

Me BnO

Baudin, J.-B.; Julia, S. A. Tetrahedron Lett. 1988, 29, 3251.

ẠY

A: Formation of a morpholinesulfenate. B: [2,3] Sigmatropic rearrangement. C: Extrusion of SO2 through a six-membered transition state.

C093 HO

Tf 2O pyridine

OTf

O EtO2C Me

Mo(CO)5

CO2Et

Mo O (CO)5 Me

Mo(CO)5 Me

CO2Et

H H

H Mo O (CO)5 Me

CO2Et

IC IA L

Mo(CO)5

E O

Me CO2Et

CO2Et

Harvey, D. E; Brown, M. F. J. Org. Chem. 1992, 57, 5559.

A: Formation of a Fischer carbene complex. B: Intramolecular alkyne metathesis. C: Intramolecutar D: Reductive elimination to form a cyclopropane.

rearrangement ( ref A042) via a boat-like transition state.

Ot-Bu

C094

Me Me

Me Me Me

MeOH

O A

Me O O

ẠY

O Me

-H

KÈ

O O O

MeO +

O HO

E: Divinylcyclopropane

alkene metathesis.

Et3N Ac2O

MeO O

MeO

OMe O

Et3N

MeO

Me CO2Me

MeO B

AcO

Me Me

IC IA L

Srikrishna, A.; Anebouselvy, K.; Reddy, T. J. Tetrahedron Lett. 2000, 41, 6643.

A: Ozonolysis of the less hindered olefin in MeOH to form a hydroperoxide ( ref Bl16, Bl17). B:

Grob-type fragmentation.

C095 H

Me O

Me H

OSiMe3

Me H

OSiMe3

SiMe3

Me3Si OTf

Fujita, T.; Ohtsuka, T.; Shirahama, H.; Matsumoto, T. Tetrahedron Lett. 1982, 23, 4091

Wagner-Meerwein rearrangements.

KÈ

C096

MeO

H3O+

MeO

ẠY

OMe

H OH Me

OH2 OH Me

H MeO OH OH Me

O OH Me

TsOH H2O

OH2

-H2O

O -H+

OH2 Me

Dechoux, L.; Agami, C.; Doris, E.; Mioskowski, C. Eur. J. Org. Chem. 2001, 4107. A

-Elimination of the epoxide to form a carbene. B: Cyclopropanation. C: Cleavage of the electron-

IC IA L

rich cyclopropane ring. D: Cleavage of the cyclopropane ring.

C097 Me3Si

Me3Si

CO2Me

OMe

MeOH

O O S Me CF3

KÈ

S O

Me O CO2Me

CO2Me

TFAA DMSO C

CO2Me

ẠY

CO2Me

CO2Me B

O CH3 Br

CO2Me

AgNO3 A g MeOH

Me3Si CO2Me

CO2Me

Me3Si Br

CO2Me

Br Br

CO2Me

Fleming, I.; Michael, J. P. J. Chem. Soc., Perkin Trans 1 .1981, 159. B: Wagner-Meerwein rearrangement followed by desilylation.

C: Swern

A: Bromolactonization.

oxidation.

C098 HO

NH2OH CN

-H2O

H O

160oC

CN O

N O

IC IA L

Stockman, R.A. Tetrahedron Lett. 2000, 41, 9163.

B: Intramolecular 1,3-dipolar cycloaddition.

C099

TBS

Ph2S

HBF4

Ph2S

TBS

TBS O

-unsaturated nitrile.

TBS

H O

KÈ

ẠY

MeO

TBS O

PhSSPh NaOMe

-H

OH H

PhS SPh

TBS

OH H

TBS O

PhS

OH H

TBS

O PhS PhS

TBS O

PhS PhS

H O

TBS workup

MeO

+H C

PhS PhS

O H H

IC IA L

Kwon, O.; Su, D.-S.; Meng, D.; Deng, W.; D'Amico, D. C.; Danishefsky, S. J. Angew. Chem. Int. Ed. 1998, 37, 1880.

A: 1,2-Addition of the sulfur ylide followed by formation of an epoxide in an SN2 fashion. B: Cleavage

of the epoxide induces 1,2-migration to form a cyclobutanone via a stable tertiary carbocation. C: Ring

opening of the cyclobutanone by the proximal alkoxide is facilitated by formation of the sulfur-stabilized carbanion.

C100 CO2Me

S Cl

H Y KOMe

SmI2

CO2t-Bu N oc B Cl

-SO2

OTs

CO2t-Bu N Boc

M ẠY

Me H

SO2 OTs

KÈ O2 S

CHO2Me

SO2

CO2t-Bu N Boc

CO2t-Bu N oc B

CO2Me

O2 S

Me H

O H

CO2t-Bu N Boc

SmI2

Cl Me H

CO2t-Bu N oc B

D N Boc

CO2t-Bu

workup +H+

O2 S

m O S I2 H

CO2t-Bu N oc B

m O S I2

Me H

OTs

SO2

mCPBA

CO2t-Bu N oc B

CO2Me

CO2t-Bu N oc B

CO2Me

OTs

CO2Me

Cl S

CO2Me CO2t-Bu N Boc

Bachi, M. D.; Melman, A. J. Org. Chem. 1997, 62, 1896. A: Formation of an episulfonium salt followed by attack of chloride ion at the less hindered carbon. B: Cyclization proceeds by an SN2 mechanism. C: SET. D

-Cleavage followed by extrusion of SO2

and elimination of a chloride radical.

MeO

A S

MeO

IC IA L

C101

OMe

hv D S

OMe

Wu, J.-Y.; Ho, J.-H.; Shih, S.-M.; Hsieh, T.-L.; Ho, T.-I. Org. Lett. 1999, 1, 1039. B: Thermally allowed suprafacial

A: Photo-induced 6e conrotatory etectrocyclic reaction.

1,9-hydrogen shift. C: 6e Electrocyclic reaction. D: Photoisomerization of the (Z)-olefin.

C102

Me3SiO

BF3 EtO OEt

Me3SiO

OEt

ẠY

KÈ

Me3SiO EtO

Me3SiO

Me3SiO EtO

CF3CO2H

A Me3SiO Et O H O

+H+

X e M 3Si O

X O SiMe3

B Nakamura, E.; Kuwajima, I. Org. Synth., Coll. Vol.

A: Mukaiyama aldol reaction. rearrangement).

1987, 17.

B: Preferential migration of the carbonyl carbon (Pinacol

C103

HCHO

F S O O

MeOSO2F

Me N

-H2O A

HN H

NaBH3CN

-H2O

NH2OH

IC IA L

LiAlH4

Me H N

B: 1,3-Dipolar cycloaddition.

C104 CO2Et

AcO

CO2Et

O Me

OAc

MeO

A: Formation of a nitrone. ref A065.

Oppolzer, W.; Petrzilka, M. J. Am. Chem. Soc. 1976, 98, 6722.

KÈ

OAc

ẠY D

CO2Et

OAc

AcO

CO2Et Ar

AcO

CO2Et

MeO

OAc

MeO

OAc

O H AcO

OEt OAc

C Ar

CO2Et

Ar H

AcO

Ar C O

AcO

AcO Ar

MeO

OAc

MeO

OAc

CO2Et

AcO

CO2Et

H AcO AcO Ar

CO2Et

AcO H AcO AcO Ar

CO2Et

AcO

OAc AcO

IC IA L

AcO

Serra, S.; Fuganti, C. Synlett. 2002, 1661.

A: Generation of a ketene via a mixed anhydride. B: Benzannulation. C: Michael addition. D:

Formation of a ketene. E: 6e Electrocyclic reaction. F: Michael addition.

Me Me O

KÈ

H2 Pd/C B

ẠY

Me Me O

C105

Me Me O O

H H

H Me Me O

H H

H Me Me O

O Singh, V.; Prathap, S.; Porinchu, M. J. Org. Chem. 1998, 63, 4011.

Oxa-di- -methane rearrangement. A: nring.

B: Reductive cleavage of the cyclopropane

C106 Ph

Ph O

N N

-N2 A

N N

O O

IC IA L

H H

Ph H

Lee, H.-Y; Kim, Y. J. Am. Chem. Soc. 2003, 125, 10157.

A: Thermal decomposition of an a ziridinylimine to form a diazoalkane. B: Cleavage of the epoxide followed by elimination of N 2 to form an alkylidene carbene. C: C yclopropanation. D: Homolytic

cleavage of the strained cyclopropylidene ring to form a trimethylenemethane diradical. E: Radical

addition.

Cl Cl

C107

KÈ S

-H+

-S B

ẠY

Parham, W. E.; Koncos, R. J. Org. Chem. 1961, 83, 4034.

A: 2e Electrocyclic reaction. B: 6e Disrotatory electrocyclic reaction. C: Spontaneous loss of S.

C108 O H

NH CN

N H

O N

H H

H ClCO2Me

H OMe

OMe

KOH

O O

OMe

Cl OMe

IC IA L

H OMe

Earley, W. G.; Jacobsen, E. J.; Meier, G. P.; Oh, T.; Overman, L. E. Tetrahedron Lett. 1988, 29, 3781.

A: Anion-accelerated aza-Cope rearrangement.

C109

mCPBA

ẠY

TBSO

-H+

BrMg

TBSO

Cl Pd

Cl PdCl

TBSO

OH PdCl2

workup

O H

TBSO

O OH

O HBF4

TBSO

KÈ

TBSO

TBSO D

Me O

H PdCl Me O

TBSO

Cl H Pd Me O

Me O

Me TBSO

TBSO

-HCl -Pd(0)

IC IA L

ClPd

Nemoto, H.; Miyata, J,; Yoshida, M.; Raku, N.; Fukumoto, K. J. Org. Chem. 1997, 62, 7850.

A: Epo xidation of the strained olefin. B: Cleavage of the epoxide to form a stable benzylic cation. C:

of the olefin with PdCl 2.

1,2-Migration to form a cyclobutanone ( ref A099). D: Ring expansion reaction initiated by o xidation E: Intramolecular carbopalladation.

-Elimination.

ẠY

KÈ

hydropalladation and 6-elimination process to give the more stable endocyclic olefin.

G: Reversible

IC IA L FF O N Ơ N

NaOEt)

OEt

H3C OEt

ẠY

KÈ

Br CH3

Brønsted

H+

O O

O R'

O C

H R

O C

H R

IC IA L

O C

B 2.0

C 2.5

N 3.0

Na 0.9

Mg 1.2

Al 1.5

Si 1.8

P 2.1

K 0.8

Ca 1.0

O 3.5

F 4.0

Be 1.5

S 2.5

Cl 3.0

Br 2.8 I 2.5

Li 1.0

H 2.1

A-

+ H2O A

+ H3O+

KÈ

ẠY

PKa

p Ka

log Ka

A-

H3O + HA

PK B (HA)

HB PKa

B-

HB Keq

pKa

+ B-

pKeq

A-

log

HA B

+ HB

pKa HA

pKa HB

PKa pKa = 13)

(NaOEt,

EtO

O +

OEt

EtO

EtOH 0) pKa = 16)

IC IA L

EtO2CCH2CO2Et;

EtO

OEt

EtOH

pKa EtOH =13 16=-3

Keq=103

pKeq=pKa malonate

Keq

50 LDA

(LDA

npKa = 36

PKa

. n-

LDA

pKa = 24

PKa

pKa = 17

ẠY

KÈ

pKa = 4.8 f

i-Pr

PKa

n-BuLi

i-Pr

N H i-Pr

N Li i-Pr

(LDA)

PKa=

LDA; PhCHO;

O EtO

OH Ph

EtO

AcOH

i-Pr2NH

IC IA L

n-Bu

CH3

O n-BuH

i-PrN

EtO

CH3 24

i-Pr2NH

EtO

O H

CH2

EtO

AcOH 4.8

OH AcO

EtO

pKa pKa

pKa

pKa = -6

0) pKa

(pKa = 15.7

ẠY

KÈ

MeSO2Cl Et3N CH2Cl2

O Me S O O

NuR

O Me S O O

pKa ([H2O]

pKa 55.5 pKa

pKa

O HO S O O

O Cl

O e M S OH O

KÈ

H r A O R

Y OH

O ClH2C

PhOH

H3O

H2O

HO OH

NH2

EtOH

O C O HO PhO HO O

Me NOH

EtOH2

NH2

ClH2C O

R O R

O S

O HO P O OH

Ar O R

O HO P OH OH

HO C O HO

H R O R

F3C

O O S O O

NH2

O HO S O O

O S

O e M S O O

ArOH

O r A S O O

ArOH2

ẠY

O r A S OH O

F3C

OH R

NH2

O N O O O

O N OH O

IC IA L

O HO S OH O

NO Me

aminonitrile

A011

abnormal Claisen rearrangement C032 acetal A008, A009, A010, A063, B084, B 116 Achmatowicz reaction C013, C079 acid chloride A003, A025

Arbuzov reaction ate complex

acyl azide A058 acyl cyanide B061, C050 acyl transfer B007, Bl13, Bl14, C007, C035, C068 acylation B060, C012, C029, C050

azirine azlactone

acyliminium ion acylium ion acylnitroso compound acyloin condensation acylpalladium species

Bartoli indole synthesis Barton reaction

B033, B038, C028 B101, Bl19 C 106

IC IA L

atom transfer reaction aziridine aziridinylimine

B056, B080, C038 A019, C009

A054

C066 B097, C014

B Baeyer-Villiger oxidation

Barton-McCombie deoxygenation A051, B071, C089 Beckmann fragmentation A015

C041, C051 A003, A036, B068 B120 Bl15 C087

A070 A028, B002

Beckmann rearrangement benzannulation

A008, A010, A021, A049, A052, B008, B012 to carbonyl group A001, A002, A003, A004 to electron-deficient aromatic ring A040, B022

bromination A010, A024, A025, A027, B087, C036, C063

addition-elimination C002 aldol reaction A020, B052, B053, Bl13 aldol reaction intramolecular C025, C027, C083 1, 2-alkyl shift

Cannizzaro-type reaction B052, C026 carbamate-type protective group for amines

KÈ

ẠY D

A036, A047, A048, A054, B119, C004, C063 allene A061, B028 allenylpalladium species C060 allenylsilane C081 rc-allylpalladium complex allylsilane

B021, B040, C060 B078, C051

A055, C014 C 104

benzyne B012, B065 Birch reduction A038, A039, B011 Bischler-Napieralski reaction A034

Brook rearrangement

addition 1,2A016, C042, C099 conjugate B046, B094, C006, C019, C086, C029 intramolecular

C042 C

B019, B020, B021 carbanion B006, B047, B049, C099 carbene A059, A061, B075, B103, C021, C064, C089, C096 alkylidene B036, B049, C016, C037, C054, C055, C083, C106 dialkoxyC046 dibromodichlorocarbocation

A061, B075 A035, B076

A030, A036, A046, A047, A048, A049, B015, B023, B051, B068, B078, B085, B108, Bl19, C063, C070, C081, C099, C109

of S--N bond of S-O bond of thiirane

C048 C048 C074

carbon monoxide carbonyl oxide carbonylation carbopalladation carbotitanation

of c~-lactone oxidative

B081 A044

IC IA L B092, C090, C108 C004, C077

Corey-Fuchs reaction B049, B077 Corey-Winter olefination B103 CSI (chlorosulfonyl isocyanate) B064

Curtius rearrangement cyanohydrin cyclization 5-endo-trig 5-exo-dig

[2 + 2] cycloaddition cyclobutane

C052, C054, C080 A066

azaC017, C067, C069 Claisen-Ireland rearrangement B093, B124 Claisen-Johnson rearrangement B091 Claisen-Schmidt reaction C038 cleavage B004, B070, B103, C046, C076

A029, B 116, B 117 B018, B038, B039, B069, B080, B097, C055, C106 C038 C012

heterolytic homolytic

KÈ

of azirine ring of C-N bond

ẠY

of C-S bond B044 of cyclobutane ring C052 of cyclobutene B054 of cyclopropane ring A060, B015,B084, C020, C043, C046, C089, C096

of cyclopropanone B057 of endoperoxide B034 of epoxide B003, B023, B051, B071, B102, Bl10, C001, C006, C013, C099, Ct06, C109 of four-membered ring of N-N bond

C059 C022

A058 B005 C019 C073

cheletropic reaction B030, B080, B101 chlorination B089 Claisen condensation C045 Claisen rearrangement A062, A063, B094, C009, C024, C062, C073

azaoxy-

cation cyclization B108 cation-olefin cyclization C003, C056 C-H insertion B036, B049, B075, B080, C016, C038, C083, C089 charge-transfer complex B063

reductive A029, B035, C079, C091, C105 Cope elimination A053, C072 Cope rearrangement C040

B042, B068, B127, C069 C049 C087 A075, C010, C087 B128

cyclobutanone C099, C109 cyclopropanation C106, B075, B076, B126, C021, C042, C046, C055, C096 cyclopropane cyclopropanone

A061, B128, C020, C093 A060 D

Dttz reaction

B127

Dakin reaction A056 Danheiser annulation C081 DCC (N,N'-dicyclohexylcarbodiimide) A007, B014 decarboxylation A023, A039, A057, B001, B019, B051, C023 dehydration deprotonation desulfurizatio diazo coupling diazo transfer reaction diazoalkane

B062 A002, A019 B103, C074 A037 B055 C064, C106

B083 B010, B024, B059, B122 A037, B013, B065, B081, B082 A021 A064, B027 C056

Dieckmann condensation Diels-Alder reaction aza hetero

A014, A053, B037, B090, B094, B124 A061, B049, B075, C021, C064, C089, C096 A073, A075, B060, B128, C021, C024, C061, C084, C109 C087 C029

-carbon enamide

IC IA L

diazoketone diazomethane diazonium salt

B120, B125, C018, C035, C044, C048, C091 intramolecular B025, B027, B028, C005, C013, C040, C044, C084 inverse electron demand B088, C091

enamine A022, B008, B046, B047, B054, B112, C022

retro A064, B027, B088, C044, C064 dienone-phenol rearrangement A048 1, 3-dipolar cycloaddition C022, C031, C079, C091 intramolecular

oxyenol

B034, B035, C079 A067, A068 C085

endoperoxide ene reaction Magnesium-

B121, C032 A013, A024, A025, A032

enol lactone enolate

B099

B029, B096, C023, C098 of azomethine ylide B096 of carbonyl ylide C015 of diazomethane B122 of nitrile oxide B089, B090

A027

A010, A039, A063, C024, C025

enol ester enol ether

A018, A019, A020, A021, A023, A060, C019 episelenide B102 episulfide B044

episulfone episulfonium salt

double inversion E1 elimination E2 elimination electrocyclic reaction 2e

B104, C076, C089, C096 Eschenmoser fragmentation B004

ẠY

KÈ

of nitrone A065, B029, C098, C103 of ozone A029, Bl16, Bll7, C049, C050 diradical C021, C038, C080 divinylcyclopropane rearrangement C042, C093

4e 6e

B081 B019 B044, B049, B104 B076, C107

B122 C100

epoxidation C013, C109 epoxide A056, B003, B004, B023, B040, B045, B058,

Eschweiler-Clarke methylation A053 ester A001, A002, A007 esterification A002, A007

A066, B025, B026, C008. C054 B087, B106, B126, B127, C008, C041, C054, C057, C101, C104, C107 C057

elimination syn-

F~H Favorskii rearrangement Ferrier rearrangement Fischer carbene complex Fischer indole synthesis fragmentation

A060, B057 C025 B127, C069, C093 B031, B082

B004, B070, B 103, C046, C076 Friedel-Crafls acylation A036, C059 Gabriel synthesis A052

hypobromite

Gilbert reagent Grignard reagent

B036 A004, A005, A006, A016, A074,C066, C085 Grob fragmentation B016, B086, C027, C044, C094

imide iminium ion

group transfer reaction B074 Heck reaction A075 Hell-Volhard-Zelinsky reaction A025 hemiacetal C001, C076 hemiaminal A005, A011, B001

insertion of carben

Hofmann rearrangement A057 Hofmann-Lrffler-Freytag reaction B033 Horner-Wadsworth-Emmons reaction A071, B036, B099 Hosomi-Sakurai-type reaction C053, C062

intramolecular carbopalladation C061, C087, C 109

B038 I~K B113 A005,A011, A012, A013, A018,

A059, A061, C054. C064

of carbon monoxide

C101 B043 A025 A019, C009

ẠY

1,9hydrogenation hydrolysis of acid chloride of azlactone

of borate A028 of ester A001, A023 of N-methyl-N-nitrosulfonamide B024 of nitrile A011 hydrometallation B042, B043 hydropalladatio hydroperoxide

C109 C094

A045, B040. B109 A026. B084 A026

inversion iodination iodoform reaction

KÈ

A053, B002, B052, C026, C030 hydroboration A028, B086, C030 hydroformylation B042 hydrogen shift 1, 5B027, B030

B042, B127. C069 C026

of carbonyl group

ipso-substitution isocyanate isocyanide Jones oxidation ketene

hydrazone A017, B003, B004, B031, B050, B082, C006 hydride abstraction B068 hydride shift A077 hydride transfer

IC IA L

A033. A053, B046, B047, B078, B114, C007 iminophosphorane B100 indole B031, B047, C038. C066

C009 A057, A058 B048, B065. B118,. C007 A068 A059, A066, C052, C067 L~N

lactam lactol lactone macrocyclic lactonization bromoiodo-

A055 C013, C079 A054. B058 B111 B114 C045 B066, B115 C097 B058

selenoB124 leaving group A002, A017, A058 Leimgruber-Batcho indole synthesis B047 lone pair A001, A002 malonate A018, A023, A040 Mannich reaction

A013, B001, B092, B111, C071, C091 Masamune-Bergman cyclization C011 Meerwein arylation B013

oxazoline oxidation of alcohol

Meerwein-Ponndorf-Verley reduction B002, C031 Meisenheimer complex B022. C002 mercury(II) triflate A032. B108 metathesis

of palladium (0) oxidative addition

IC IA L

B089, B120, C014, C098 A002, C036

oxymercuration oxypalladation ozonide

A031, A032, C025 A077 A029

oxonium ion

ozonolysis A029, B116, B117, C049, C083, C094 P

palladacycle

C087

migration A028, A055, A057, C075, C099, C102, C109 Mitsunobu reaction A045, B079, C065 mixed anhydride

A077

A076, B042, B043, C061, A075, B105, C010 oxime A014, A015, A055, B070,

B066, B070, B123, C098, C104

A042, A043, B014

alkene A078, B 109, C034, C093 alkyne B109, B127, C034, C093 enyne B109, C034 Michael addition B004, B005, B006, B008, B053, B054,

B048

palladium-mediated reaction A075, A076, A077, C010,

Neber rearrangement B056 nitrene B080, C038 nitrile A005, A014, A015, B062, B064 nitrile oxide B089, B090, B120 nitrilium ion A011, A034, A049, B065

peroxide Peterson olefination

nitrite B097, C014 nitrone A065, B029, C078, C098, C103 Norrish type I reaction C080 Norrish type II reaction B125 N-oxide A053, B062

phosphonate A070, A071 photo-cleavable protecting group B098

ẠY

KÈ

A003, A019, A058, B007, B060, B061, C012, C023., C051, C104 Morita-Baylis-Hillman reaction B053 Mukaiyama aldol reaction C102 Nazarov reaction B026, C003, C039

O organochromium species organosamarium species orthoester

B041 B107 B084, B091, C070

orthoformate oxa-di- -methane rearrangement

A009 C105

partial reduction Perkin reaction

C060, C061, C087, C109 C051, C057 B007

Pfitzner-Moffatt oxidation phenonium ion phosphinite ester

A054, A056, B018 A074, C016, C051 B014 B084, B111 C082

photo-induced homolytic cleavage B072, B074, C014 photoreaction B032, B033, B097, B125, C014, C041, C080, C105 Pictet-Spengler reaction A033, B051 pinacol rearrangement A047, C088 protodesilylation proton transfer

C005, C023

A008, A009, A011, A012, A013, A014

protonation A001, A002, A005, A006, A008, A009, A011, A054, A063 Pummerer rearrangement pyrylium ion

Robinson annulation Robinson-Schöpf reaction ruthenium carbene complex

B037 C079

B008 B001

A078, B109, C034

Q~R

samarium(II) iodide A066, B025

B111 A068

selenoxide A073, B124, C024 Shapiro reaction B050 [2, 3] sigmatropic rearrangement

A068, B095, B106, C033, C037, C047, C048, C092

[3, 3] sigmatropic rearrangement A062, A063, B031, B091, B093, C047, C058, C066, C068, C071, C075, C078

radical A031, A050, A051, B013, B017, B018, B032, B033, B038, B039, B071, B072, B073, B097, B107, Bl18, C011, C028, C043, C052, C063 radical addition C028, C106

Schmidt reaction selenimn dioxide

B030 C082 C040 C035 B063

azaquinone o-quinone monoacetal o-quinonemethide p-quinonemethide

B107, C015, C043, C100

o-quinodimethane

IC IA L

silametallation silicate ion

B105 B105

silyl enol ether single electron reduction single electron transfer

C049 B041

radical anion A038, A039, B069, B073 radical chain reaction A050, A051, B013, B017, B018, B032, B033, B038, B071, B072, B073, B074, B 118, C028, C(163

KÈ

radical cyclization B107, C011 5-exo-dig B017, C043 5-exo-trig B017, B071, B074, BllS, C011, C043, C052 transannular B018

ẠY

Ramberg-Bäcklund reaction B072, B122 RCM (ring closing metathesis) A078 reductive elimination A075, A076, B042, B043, B105, B127, B128, C010, C087, C093 Reimer-Tiemann reaction retro-Cope elimination rhodium carbene complex B126, C015, C074, C075 ring contraction ring expansion Ritter reaction

A035 C072

B111, B 115 B024, B054, C109 A049

A038, A039, B011, B013, B073, B107, Bl15, C015, C043 singlet oxygen B034, B035, C079 Smiles rearrangement C002 SN 2 reaction A041, A052, A070, A072, B010, B019, B020, B059, B104, C023, C063, C082, C100 intramolecular B045, B101, B102, Bl10, C001 SN 2' reaction SRM reaction

B035, C085 B073

Staudinger reaction Stetter reaction Stobbe condensation

B101 B006 B009

Stork enamine reaction Strecker amino acid synthesis

A022 A011

sulfenate

C033

B122 B048, B050, B079 C065

sulfonation sulfoxide Suzuki-Miyaura coupling Swern oxidation

B085 B037, C033 A076 A043, C097

Wittig reaction A069, B080 intramolecular B100, B123, C086 [1, 2] Wittig rearrangement B069 [2, 31 Wittig rearrangement Wolff rearrangement

C077 A059, C054

Wolff-Kishner reduction xanthate ylide

A017 A051, C089 B103, C050

T~Y

azonmthine carbonyl

Tamao oxidation B105 Tamao-Fleming oxidation C005 tautomerization A011, A013, A023, A032, A066

A043, B014, B095, B 110, C037, C099 ynolate C045, C054

B006 B095 B125 B103 C048

thiourea A072 Tiffeneau-Demjanov-type rearrangement B024, C022 Tishchenko reaction C026 titanacyclopropane B128, C020

KÈ

TosMIC (p-toluensulfonylmethyl isocyanide) B018 transmetallation A076 trimethylenemethane diradical Cl06 Ugi reaction C007, C084

ẠY

Vilsmeier reaction A012 vinylcyclobutane-cyclohexene rearrangement C088 vinylcyclopropane rearrangement C021 vinylogous amide A022 vinylphosphonium salt B100 vinylsulfonium salt B110 Wacker oxidation A077 Wagner-Meerwein rearrangement A046, B023, B085, C095, C097 Wharton rearrangement Wilkinson complex

B003 B043, C076

B096 C015, C079

phosphorus A069, B100, B123, C019, C086 sulfur

thiazolinium ion thioacetal thioaldehyde thionocarbonate thiophile

IC IA L

sulfene sulfinate ion sulfinic acid

BÀI TẬP CƠ CHẾ PHẢN ỨNG HÓA HỌC HỮU CƠ NÂNG CAO CÓ ĐÁP ÁN 演習で学ぶ 有機反応機構 by 福山 透

BÀI TẬP CƠ CHẾ PHẢN ỨNG HÓA HỌC HỮU CƠ NÂNG CAO CÓ ĐÁP ÁN 演習で学ぶ有機反応機構 by 福山透