BÀI TẬP TỔNG HỢP HÓA HỮU CƠ LUYỆN THI HSG QUỐC GIA (TẬP 2) PHẦN LỜI GIẢI VIẾT TAY

BÀI TẬP HÓA HỮU CƠ LUYỆN THI HSG QUỐC GIA

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BÀI TẬP TỔNG HỢP HÓA HỮU CƠ LUYỆN THI HSG QUỐC GIA (TẬP 2) PHẦN LỜI GIẢI VIẾT TAY WORD VERSION | 2022 EDITION ORDER NOW / CHUYỂN GIAO QUA EMAIL TAILIEUCHUANTHAMKHAO@GMAIL.COM

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Fukuyama Group - Group Meeting Problems 01/09/2002

1

Li

Me

O

TMSO

MeO

THF –78 °C; TMSCl (1.5 eq); 25 °C; HCl aq

H

2

H

0.1 eq PhSH 0.1 eq PhSNa C16H20O2

Me O

O

THF reflux 12 hr

H

O MeN O MeO

Cl

O lutidine

1) MeAlCl2, CHCl3 2) NaBH4, MeOH, 63% (2 steps)

toluene 68%

3) MsCl, Et3N, 94% 4) t-BuOK, THF, reflux, 86%

MeO

3

CrCl2 (8 eq) TMSCl (6 eq) H2O (1 eq)

O R1CHO

NMe

+

R2

4 N

N

R1

O

R2

THF 25 °C, 24 h

Ph

OEt

O

OEt Ph

benzene reflux

H 67%

5 O HN TESO

Ar CO2Me

1) Boc2O, DMAP Et3N, CH2Cl2 Ar-C7H8NO 2) TBAF, THF-H2O 3) DMSO, H2O, 130 °C

1) Me3SiOK toluene, 70 °C; aq NH4Cl 2) Pb(OAc)4 t-BuOH, 50 °C

Cl

Ar =

N

NHBoc Ar O

Fukuyama Group - Group Meeting Problems 01/16/2002

1 O

PhSH aq HCHO Et3N

O Me

EtOH

O

1) Li/NH3 THF, t-BuOH; TMSCl, Et3N

O

Me4NBH(OAc)3 H

MeCN-AcOH –40 °C

2) Sc(OTf)3 aq HCHO THF

HO

O Me

Me OH

2 SmI2 (0.1 eq) Ph OH Ph O

H Ph

Ph OH

(4.0 eq) O

Ph

PhMe, 80 °C, 4 hr 95%

O O

Ph

3 DNs N

1) cyclopentadiene, NaIO4, MeOH, H2O 2) DNsCl, pyridine, CH2Cl2

NH2 O NHOH

3) Pd(PPh3)4, THF, ∆

N O

OH

4

+ n-Bu Ph

MeOTf 2,6-di-t-Bu-pyridine CH2Cl2, 0 °C;

1) MS 4Å CH2Cl2

OHC

2) Oxone®, NaHCO3 MeCN-H2O 54%

NH2

A

O n-Bu

aq NaHCO3 55%, >98% ee

5 Cr(CO)5

benzene

N Ph

reflux

Ph O

OHC

N

Fukuyama Group - Group Meeting Problems 01/23/2002 O

1

CO2Me N2

O

O CO Me 2

O

Rh2(OAc)4 (1 mol%) CH2Cl2 reflux, 54%

O

O

2 NO2

NO

hν

+

ROH

OR

CHO

OAc

OAc

3

Hg(OTf)2 1.2 eq tetramethylurea

H O

CH3CN r.t., 5.5 h; NaCl

HO ArCO2 Ar = p-nitrophenyl

HgCl

22%

4 Ph

TMS

DMAD (2.0 eq)

TMS

Et2O –78 °C to rt 16 hr 79%

N

A C26H35NO8Si2

TMS n-Bu

N

TMS N TMS

(1.0 eq)

TMS

O

n-Bu MeO2C

Et2O –78 °C to rt 24 hr 33%

MeO

5 Ph Ph N3

CO2Me

OMe

1) benzene, 80 °C N

O

2) PhCHO, DABCO (1.5 eq) Ph

CO2Me

CO2Me Ph O

TMS N TMS

Fukuyama Group - Group Meeting Problems 01/30/2002

1

AlCl3 (2.0 eq)

SiMe3

N OH

CH2Cl2 –10 to 0 °C 84%

NO2 O

O

OH

2

POCl3, 50 °C

NMe CHO

MeO

86%

OMe

MeO N Me

Cl

O

3 O

O

Pd(dba)2, dppp CO (6 atm) DMF

N H

NO2

74%

4

CN CN NC i-PrNH2, hυ NH3, CH3CN-H2O

MeO

NHi-Pr MeO

5

O OTIPS

Me N PMP O

PMP = p-C6H4OMe

1) ClTi(Oi-Pr)3, c-C5H9MgCl THF, rt, 90% 2) SiO2, CF3CH2OH, rt; P(OEt)3, rt, 68%

H

OH H

TIPSO

H

stereoisomers

Fukuyama Group - Group Meeting Problems 03/06/2002

1

TBSOTf (2.1 eq) collidine (4.2 eq)

O CH3(CH2)14

CH3 N OCH3

N

CH3 OTBS

HCOOH paraformaldehyde

O

CN

NH2

CH3CN reflux, 12 hr 85%

3 N

OEt

Me

O

Ph

CH3(CH2)14

CH2Cl2 rt, 3 hr 61%

2

(OC)5W

O

pentane, 20 °C 93%

O

[(COD)RhCl]2 Tungsten-carbene complex

Ph

H

N

Ph

Ph

THF-EtOH (5:1) 20 °C, 69%

Me OEt

4 MeO N

1) m-CPBA (1.1 eq) CH2Cl2, rt, 3 hr 82%

H

H HO N

2) NaOH, MeOH rt, 5 min, 71% 3) TFA, CH2Cl2 rt, 15 hr, 52%

N MeO2C Cl

5 1) Li S 2) HgCl2, H2O

Cl

O

N

CHO CO2Me

Fukuyama Group - Group Meeting Problems 03/20/2002

1

OTIPS

Cp2TiCl2; MeMgBr,

Br2 (2 eq)

MgBr

2) Pd-C, HCO2NH4, MeOH reflux

Me

t-Bu N O Cu O N t-Bu

2 Me COCN2CO2t-Bu

Pentacyclic compound

( racemic )

3

O MeO2C

NBS, TMSN3

COPh

heat in toluene

PPh3

4

CO2Et

5

1) NaBH4, MeOH 0 °C 2) NaH, BnBr, DMF 0-23 °C

N MeO2C

Ti(Oi-Pr)4 2 i-PrMgCl

TBSO

O

O

TBSO

1) 30% aq HCl reflux, 18 h

cat. Cu(bpy)Cl "Olefin" ClCH2CH2Cl reflux, 48 h 66%

2) pH 13

O

Br

1) FeCl3 2) AcONa

N

N H

Me

Ph

C12H24O2Si

Et2O

N Cl CO2Me

Me

3) DIBAL, CH2Cl2 –10 °C 4) Tf2O, 2,6-lutidine CH2Cl2, –78 °C

toluene reflux

O

3

1) BnNH2, Pd2(dba)3, P(o-tolyl) NaOt-Bu

OTIPS ;

OBn

Fukuyama Group - Group Meeting Problems 04/03/2002

1

Cl

O

O O

O

N

AcO

O

TFA

+

O

OAc

H

N

O

H OH

AcO

AcO

OAc

H

AcO

2 HN

1) A, Et3N dioxane, 25 °C 2 days, 84%

NH2

2) dimethyl fumarate 170 °C, 8 h, 84%

Ph

Cl

Cl

Cl

ethylene, Na2CO3

Cl

CCl4, 170 °C

MeO2C

N

Ph NH

MeO2C O 1) KOH, MeOH 85 °C

A

+

2) H3O , CH2Cl2

3

OH

O O

Br

1) DBU

O

O 2)

O

3) NBS, H2O

O O

4) KOt-Bu (3 eq)

O

O

4

H

SPh O O

1) NaH 2) m-CPBA

MeO

CO2H

3) KOMe, MeOH OH

OMs (racemic)

5 O

SiMe3

O 1) 300 °C, neat 2) Pd(OAc)2, CH3CN

OH

Fukuyama Group - Group Meeting Problems 04/10/2002

1

MeO

MeO

O

MeO

1) CSA, benzene, reflux 2) NaI, acetone

SEt

N

CO2Me

N H

MeO

3) NaH, THF, reflux

2

O

Me

SEt

H

MsO

O

O

OAc Me

OAc 1) NaBH4, MeOH

OAc

2) p-TsOH, benzene

Me OAc

3 HO

NaHMDS; DMAD

O P(OEt)2

O

O

CO2Me CO2Me

toluene

O

+

CO2Me

P(OEt)2 O 37%

29%

4 S

S PhO

S NPMP

5

N PMP

O *Ti/graphite, DME

Cl

Ph

Ph Cl COOEt

reflux, 1 h

NMe O

SH

AlEt2Cl CH2Cl2, rt 67%

O OEt

94%

O P(OEt)2

N Me * Ti/graphite was prepared from K + 8C(graphite) + TiCl3

Fukuyama Group - Group Meeting Problems 04/17/2002 1 N

H N

NH2

Bu3SnH AIBN

SeO2

O

A AcOH ∆ A contains Se atom

2

1) t-BuOK EtCOCl –78 °C

O

CO2CH3

CO2CH3

H2SiF6

(xs)

HOOC

∆

2) NaHMDS TBSCl –110 °C

3

benzene 80 °C

H N

H N NCS, CCl4; MeOH rt, 40 min.

+

A

MeO AgNO3 A MeOH 5 °C, 20 min.

4

15 eq CO2t-Bu 0.67 eq PhSSPh cat. AIBN CO2t-Bu

benzene reflux

N OMe

CO2t-Bu t-BuO2C

53%

5 O Ph

1) 10% KOH MeOH-H2O, reflux 2) (MeO)3P, EtOH, reflux

Ph

S H

N CO2Me

3) MeSLi, DMF, 0 °C 4) (HCHO)n, CSA, Na2SO4 MeCN, reflux

O Ph N

Fukuyama Group - Group Meeting Problems 05/01/2002 1

1) LHMDS (2.2 eq), THF; I2 2) Cu(OTf)2, CH2Cl2

NHBoc CO2Me

Ph

OH CO2H

Ph 3) LiOH, H2O

NH2

O

2

Ph Ph

Ar N

Ph

(2.0 eq) N

O

Ph

Ar

Ph

N N

xylene 140 °C, 20 min

Ph H

Ar = p-MeOC6H4-

57 %

3 O

H

O

t-BuOK, t-BuOH; H+

SO2Me

30 % O

O

O

O SO2Me

Me

4 O

1) i-amyl nitrite*, HCl Et2O, 5-15 °C, 1 hr

CH(OMe)2

3) hν, Pyrex C9H4N4O MeOH, 3 hr 69%

2) NH3*, NaOCl*, NaOH H2O, 10-20 °C, 1.5 hr 47% (2 steps)

CH2CO2Me

*: 理論上2 eq.

Me

5

N N

OH

N H

Me

CHO

TsOH, PhH, reflux

n-BuLi, –78 °C; Me

O

CHO

–78 °C to rt

N Me

Fukuyama Group - Group Meeting Problems 05/08/2002

1 1) HCHO, Me2CHNO2 2) Raney-Ni, H2

NH2

H N

cat. BTAC , cat. NaCN , acetone (2 eq) CHCl3 (1.5 eq), CH2Cl2 , 50% NaOH

Ph

N

0-5 °C

O

Ph BTAC: benzyltriethylammonium chloride

2 (Me3Si)3SiH AIBN, PhH (Me3Si)3Si

∆, 4 h 89%

O CH2

O

3 PhNH2

4

Ph

EtOOC

1) EtOH, reflux, 66% 2) PhCOCl, Pyr, 81%

OH CN

Ph

3) HBF4, AcOH, 70% 4) CH2=CHCOOEt, DMF, 65 °C 75%

SmI2

O

C3H7

Ph

C3H7

+

OH 2:1

68%

5 O HN HN

O +

O

O

2eq Pb(OAc)4

CHO

CH2Cl2

Ph

Ph

OH

benzene-HMPA

N H

O

C3H7

I

H

N N HO2C

O 64%

Fukuyama Group - Group Meeting Problems 05/15/2002

1

MeO Br

OMe Br

Br

Br

2

1)

OAc

CO2Me

3) PDC, CH2Cl2 4) heat, neat

toluene, reflux 2) K2CO3, MeOH

5) Bu3SnH, AIBN benzene-THF

N3

1) TfOH, benzene, 0 °C; NaOH aq (work up) 82 %

Ar

2) Pd/C, H2 94 %

OH

N Ar

Ar = 3,4-(methylenedioxy)phenyl

3 piperidine, H2O

CN CO2Me

S

4 Piv Ph

N

rt, overnight 69%

1) LDA, THF, –78 °C 2) HCl/Et2O; ClCO2i-Bu, NMM N-Bz-Gly

Boc

O N

MeO2C

3) TsOH, PhMe, ∆ 4) Boc2O, DMAP

H2N

1) LDA, THF, –78 °C 2) HCl/Et2O; ClCO2i-Bu, NMM N-Cbz-Gly

CN CO2Me

S

t-Bu O Ph

O N

NMM = N-methylmorpholine

5 O O

TMSCHN2, n-BuLi DME, hexane; O silica gel 64%

HO

O

N N

3) TsOH, PhMe, ∆

Ph

O

NHCbz

Fukuyama Group - Group Meeting Problems 05/22/2002

1 N3

Me

O

R

H

H

N

1) PhH, rt overnight, 73% 2) n-PrOH, reflux 2 h, 70%

O

Me R N

3) N-methylpiperazine reflux, 4 h, 65%

O

O N

N

O

N

R=2,4-chlorophenyl-

2 O

1) –80 °C to rt 2) NaHMDS; Davis' oxaziridine

OLi SiMe2t-Bu

+

MeO2C TBSO

3) LTA MeOH-PhH

t-Bu

t-Bu

CHO

3 O

H

O H

O O

H

p-TsOH ∆

hν

O OMe

H

1) MeMgBr 2) POCl3, Pyr

H

O

O

3) Pd(PPh3)4 PPh3

O

O

4 Me

I(OAc)2 Me

SiMe3 BF3·Et2O

I

I

Me

Me

Me

30%

47%

5 EtO2C Ph

N H

Me

+

O

1) OEt , hν, 0 °C, 55% 2) DBU, benzene, reflux, 70%

EtO

O

3) DDQ, benzene, reflux, 65% 4) NaOAc, MeOH, reflux, 80%

Ph

CO2Et N

CO2Me

Me

Fukuyama Group - Group Meeting Problems 06/05/2002

1 O

O

CO (2 atm) [Rh(CO)2Cl]2 (5 mol %)

O

dioxane 60 °C, 24 h; workup H3O+ 97%

O

H

O

OH

2 Br Br

1) n-BuLi, THF, –100 °C; O

H H

Ph

3) Co2(CO)8 DME rt to reflux

B O

–100 °C to reflux

3

H

O

H

Ph

2) H2O2, NaOH

N hν

NH N

NH3, MeOH;

NH2 CO2H

CO2

N H

78%

4 Me

O

Me OTBS

HO

5

1) H2NOH•HCl, Py reflux

3) Al(Oi-Pr)3 N-methyl-4-piperidone toluene, reflux, Dean-Stark

2) LiAlH4, THF reflux

4) aq. HF, MeCN 5) NaNO2, H2O, AcOH

Me OH

O

1) LDA (2 eq); CO2H

I 2) (COCl)2; Et3N, toluene reflux

3) MeLi 4) Mn(OAc)3•H2O Cu(OAc)2 EtOH, rt

O

Fukuyama Group - Group Meeting Problems 06/12/2002 1 H3CO2C

O Rh2(OAc)4,

CH3 N

COCH2OH

CO2CH3

CH2Cl2, rt, 1.5 h; silica gel

COCHN2

N

CH3

84%

2

O

O

NaHMDS, THF; +

OMe

NC

NEt2

NEt2

aq. NaOCl

N

N

O 71%

3 O

LiCHBr2, THF; n-BuLi (2 eq),–78 to 25 °C;

O

A OH

quenched with i-Pr3SiCl hυ (vycor)

A

N2

O

OSii-Pr3

ClCH2CH2Cl rt 3.5 h ; 2 h

O

O

OSii-Pr3

4 CO2Me N2 OMe

N O

Cu(II), PhH, reflux

MeOH, 60 °C

86%

95%

N

O

O Cu(II) ; Copper trifluoroacetylacetonate

5 HS N MeS

MeO

Ts Me3Si

NaI, NaOH

CsF, MeCN

EtOH, reflux 71%

4-Methoxybenzaldehyde 85%

Cl S

Fukuyama Group - Group Meeting Problems 06/19/2002

1 NO2

MeO2C

1) PhNCO, Et3N hexane, 50 °C;

2) HCl aq THF, rt

O

A O

O

4) NBS DMF 0°C;

O O N

3) NH2OH·HCl Py, rt

Et3N; A, rt

96 % (2 steps)

70-90 %

MeO2C

N

O

2 Cp2ZrCl2(1.05 eq), n-BuLi(2.1 eq), THF, –778 °C; added SM, –78 to –20 °C; PhNC, 70 °C; MeOH 21% overall

PhHN H Me H racemic

3 1) DBU, 80% 2) TsOH, MeOH refux, quant.

O O

+

CN

CO2Me

CO2Me

O

4 1) O

N

Et3N; H3O+, 82% 2) AcCl, py, 0°C, 80%

COCl

3) hν (Pyrex), 78% 4) 4% KOH in dioxane-H2O (1:1) 100 °C, 72%

O

OH

5 1)

O

, 120-130 °C 88%

O

MeO

O

N O

2) hν, MeOH, 59%

NH

O

3) triphosgene, Et3N THF, –50 °C, 87%

O

OH

O

Fukuyama Group - Group Meeting Problems 07/03/2002

1

OTBS CHO

1) NH4OH, 62% 2) PhCOCH2Br, 2,6-lutidine toluene, ∆, 26% O

O

O

3) OHC CH2OTBS tetralin, 205-208 °C, 52%

CO2Me

O

O

2 1) Br2, MeOH-ether –35 °C, 30 min, 73%

CO2Bu

O

CO2Bu

2) 2% H2SO4 rt, 90 min, 30%

OH

O

3 1) LDA (1.1 eq), THF, 0 °C; TBSCl (1.5 eq), –78 °C, 73%

O N

N H

TMS N

2) LDA (3.3 eq), THF, 0 °C; TMSCl (3.5 eq), 65% 3) 200 °C, 82%

N

TMS

4 O Cl Ph

5

H2N

H N

Et2NH

LDA; MeI THF

MeMgI, Et2O

rt 85%

–78 °C to rt 68%

reflux 95%

PPh3 (2 eq) CCl4 (2 eq) Et3N (2 eq) CHO

CH2Cl2 reflux

1) RCOCl CH2Cl2 2) TsCl (20 mol%) Et3N, CH2Cl2

Me

Me Ph

O R

NEt2 OH

N2

Fukuyama Group - Group Meeting Problems 07/17/2002

O

1

1) NaOEt, MeI 2) conc. HCl; NaOH

O O

Et3N

O

2

Br

3) MeLi 4) conc. HBr

HS

Me

SH MeOH

N3

N

3 2) OH 1) Tf2O, pyridine

Mo(CO)5 Me

O- Me N+ 4

H

CH2Cl2, 0 °C

CH2Cl2, 0 °C

3) benzene, 65 °C

O

CO2Et

Me CO2Et

4 Br O N

O O

O

1) t-BuOK THF, 0 °C 2) Lawesson's rgt THF, rt

OH O Et

N

3) P(OMe)3

O

reflux

Et O

5 1)

N

S

Li+ CH2-

O

O S

2) Lawesson's rgt 3) BrCH2COPh Et3N

N

Ph

Fukuyama Group - Group Meeting Problems 07/31/2002

1

O

O 1) mCPBA (1 eq), CH2Cl2, rt, 86%

NH2 PhS

2) AcCl, CH2Cl2, 40 °C, 71%

SnBu3

2

OH Ph

3

NH2 AcO

O

TFAA, Py

CO2H

PhH, 80 °C

CF3

Ph

OH

N2

O O

OH CO2Et

OAc O O

SPh

1) Rh2(OAc)4, solvent 2) TFA, EtOH quant. (2 steps)

HO HO

O

COOH

OH

4 MeO2C

NO2

1) BSA (3.0 eq) ethyl vinyl ether

3) LHMDS, AcCl THF, –78 °C

2) MeOH/CH2Cl2

4) butyl vinyl ether toluene, reflux

CO2Me BuO

N Ac

BSA = N,O-Bis(trimethylsilyl)acetamide

5 O

Br

t-BuOK t-BuOH-THF 70%

O3, NaHCO3 MeOH-CH2Cl2 –770 °C; Ac2O, Et3N, DMAP benzene, reflux

O CO2Me

Fukuyama Group - Group Meeting Problems 09/04/2002 1

3) TFA, CH2Cl2, 70%

O

2

Me

HO Ph

1) CH2N2 (gas), Et2O, –78 °C, 87% 2) PhOC COPh , CH2Cl2, reflux, 63%

S

+

NH

BF4

S

O

1) EtSO2Cl, Et3N (2 eq) THF, 0 °C, 70% 2) n-BuLi (1 eq), THF, –78 °C; MoO5·HMPA-LDA in THF (1.1 eq), –78 °C; rt ; water, 45 °C, 81%

3

COPh

N Me

O

Me

O 2 eq PhP(SiMe3)2

Cl Cl

MeOH

OMe OMe

C26H38O2P2Si2 CH3CN, –15 °C

reflux, 24 h

O

O

4 CN S

N

O

O

+

CO2Et

H3C N2

[Rh(OAc)2]2 70 °C, 1 h

N

NC

CH3

140 °C, 1 hr S

O

5 BocNHNH2

1) NaNO2, aq AcOH, 10 °C 2) PPh3, Et2O

Reagent A

3) Cl3CCHO, toluene, reflux 4) Oxone, K2CO3, H2O-CHCl3, 0 °C OH MeO

OH N HN N

1) A, CH2Cl2 2) TFA 3) NIS (2.5 eq)

MeO O I

O

OH

CO2Et

Fukuyama Group - Group Meeting Problems 09/18/2002

1 H Si

H

1) NaIO4 2) heat, PhH

SiMe2Ph

3) H2O2, KF KHCO3

PhS

H HO

H

SiMe2Ph

2 O Cl

Cl

P(OEt)3 (1 eq.)

A

40 to 100 °C, 1 hr

99%

LDA, THF, –78 to 0 °C; A, Pd(PPh3)4, rt, 3 hr; O NaOH, EtOH-H2O reflux, 24 hr

O

79%

3 H3N

CO2

3) Lawesson's reagent

1) LAH

A 2) HCO2Et

OBn

hν

HCl (g) MeOH;

A 76%

I2 acetone/H2O

(OC)5Cr Me

BnO Me MeO2C

CHO

4 1) Ca(OCl)2, CO2, H2O CH2Cl2, 65%

CHO

O 2) cat. Pd(OAc)2, Ph3P, AcONa 150 °C, 66%

(E:Z=59:41)

5 MeO

Ph

N

PhMgBr (2.2 eq) N

Br

Ph Br

THF –42 °C to rt

Ph

N Ph

Fukuyama Group - Group Meeting Problems 09/25/2002

1 NC Ts

H NC Ts

1) CH2N2 (ex.), CH2Cl2 Se

2) mCPBA, CH2Cl2, – 10 °C

OH

Cl

2 aq. glutaradehyde (2.5eq) OH pH3.5 , TolSO2Na ; ZnBr2

Ph

Ph

O

N

NH2

O

R

R : TolSO2

3 OTMS

1) N2CHCO2Et, CuSO4, PhH, 65% 2) PPh3 BF4 , KF, 18-crown-6, MeCN, 82 °C, 95%

O

SPh

3) NaOH / H2O, MeOH, THF, 60 °C 4) ClCO2Et, Et3N, THF; NaBH4, THF / H2O 5) TFA, CHCl3, 43% (3 steps)

t-BuO2C

O

O

4 OHC

t-BuOOH cat. VO(acac)2

OH O

OMEM

CH2Cl2 0 °C

H

O

MEMO

OH

toluene 110 °C 48 h

H 56% (2 steps)

5 Ph N Ph

O n-Bu

OCOi-Bu OCH2OCH3 CH3

1) BF3•OEt2 (3 eq), PhSH (5 eq) CH2Cl2, rt, 1.5 h, 57% 2) W-lump, O2, rose bengal CH2Cl2, 3h, 35%

i-BuCOO H3C

n-Bu O

O

Fukuyama Group - Group Meeting Problems 10/02/2002 Me

1

Tf2O, DTBMP ClCH2CH2Cl –20 to 65 °C;

OTES N

O

O

KHCO3 aq

O

Me

H

DTBMP= t-Bu

N

t-Bu

OTDS

OTDS

2

OMOM

OEt OMOM

KOH (0.2 eq)

CO2Et CO 2Et MeO

H2O-EtOH 25 °C, 60 min

CO2Et OMe

TDS =

Si

70%

3 Ph OH

PhOC

O

Ac

COPh

O Ph3P, CH2Cl2, rt 74%

Ph

O

4 HO [Pt(C2H4)Cl2]2 toluene reflux

O

97%

5 H N

O O R

N

Cl Ph

O

R = (CH2)2CO2H

O

1) 0.03 N HCl MeOH, rt 2) O2

N

OMe N

Cl Ph

Fukuyama Group - Group Meeting Problems 10/16/2002 1

Br

CH2Cl2 reflux Ph N

O

SH

C15H10BrN4+•BBr–

Br

xs. KHCO3

NH2

N

Br Br

O

ArN2+Cl– (in 10% HCl) H2O, –2 °C;

A O

O

NaH, THF, reflux; A, –35 °C to rt

Me

N Ph

N CH3CN

ArHN

O

Ar = p-BrC6H4

2 1) NaNH2, PhBr, THF, reflux, 42% 2) Br2, AlCl3, 80 °C, 81% 3) TrN3* , KOH, n-Bu4NBr, 18-crown-6 benzene/H2O, 77%

OTMS Me

4)

Me

Me OSi(i-Pr)3

HO Br

OSi(i-Pr)3

hν, ClCH2CH2Cl, 80 °C, 60%

Me

*Tr: 2,4,6-triisopropylbenzenesulfonyl

3 1) ex. EtSH BF3·Et2O, CH2Cl2, 0 °C 2) AlCl3, CH2Cl2, 0 °C

O NO2

NO2 H

3) ex. 1,3-cyclohexadiene AlCl3, CH2Cl2, 0 °C

4

H

SEt

N N 1) Ph MeO2C

5

N H

N

Ph N N PhCl, reflux, 92%

PhI(OAc)2

2) Me3OBF4 CH2Cl2, rt, 79%

MeOH, 0 °C 75%

Li

OTMS n-BuLi, THF, 0 °C; OMe

Et

CHCl3, reflux 63%

MeO2C Me N N Ph

(OC)5Cr

–78 °C;

Ph

–78 °C to rt;

rt to 90 °C;

H3PO4, rt;

HCl, acetone rt

HO

O

Ph

H

Et

Ph

Fukuyama Group - Group Meeting Problems 10/23/2002 1 O N2

O

HO

1) Rh2(cap)4*, 61%

Me

Me

2) LiOMe, 88% 3) BF3·OEt2, 68%

O

O

O

OMe

*Rh2(cap)4: dirhodium(II) caprolactamate

2 1) NaN3, NH4Cl 2) PPh3

O SO2Ph

3

SO2Ph 4) BF3•OEt2 76%

1) 20 mol% Ni(cod)2 40 mol% PPh3, MVK ClCH2CH2Cl, rt, 18 hr 95%

t-BuO

Ts N

3) TsCl, Et3N 51% (3 steps)

2) Hg(OAc)2, H2O 40 °C, 40 hr; NaCl, rt, 16 hr 86%

3) Pb(OAc)4 PhH, 80 °C, 1 hr 91% 4) K2CO3, EtOH rt, 24 hr 65%

Ot-Bu

O

4 H

H 1) O3, MeOH, –78 °C; evapolation;

OAc

N

OH

AcO

1) ClCO2Me Na2CO3 THF, 80%

3) NaH Pd(OAc)2, Ph3P DMF, 80 ~ 100 °C 56%

2) AcCl, pyridine 77%

4) LAH, rt, 67% 5) LTA, 78%

OH

N H

THF

p-NO2C6H4COCl pyridine-CH2Cl2 0 to 40 °C

O

5

2) SmI2, Pd(PPh3)4

OH

NMe H N H

H O

Fukuyama Group - Group Meeting Problems 10/30/2002

1 OAc

O Ph

OMe (2 eq)

I OAc

COOMe

conc.H2SO4, CH(OMe)3 86%

MeO

MeO

2 OTBS

1) KHMDS, Et2O, 53% 2) TPAP, NMO, CH3CN, 92%

HN

O 3) aq. NaOCl (10 eq), MeOH; AcCl, MeOH, 49%

Br

3

O OAc Me Me H AcO

N H

OH

O OAc Me

1) OsO4, pyr OTMS 2) SOCl2, pyr, CH2Cl2, 0 °C Me

H 3) NaIO4, RuCl3, MeCN, H2O 4) DBU, CH2Cl2; acidic workup

H

H AcO

H

O

H H

OH

H

4 TfOMe2Si

N H N Ts

CO2Me

Et3N , 0 °C to rt

HF, Py; mesitylene reflux; KF, K2CO3, H2O2 MeOH-THF

OH

H N

N H Ts O

5 1) ClCH2COF, Me3Al K2CO3, CH2Cl2 0 °C, 77% N Bn

2) MCPBA, CH2Cl2 0 °C, 95%

C15H18ClNO2 (contains 9-membered ring)

H2, Pd(OH)2/C MeOH, rt, 7 days; K2CO3, MeOH 45 °C, 77%

H

OH

N O

Fukuyama Group - Group Meeting Problems 11/06/2002

1 Br

Bu2Mg (0.52 eq)

n-BuLi (1.1 eq)

DMF (~2.0 eq) –20 °C;

THF –20 °C;

–20 °C;

2N HCl

OH O

COOH

2 CHO N3

O

1) hν CHCl3, rt, 8 h 2) PPh3 toluene, reflux, 3 h

CO2Me N

3) methyl propiolate toluene 140 °C, 12 h

CO2Me

+ N

3 N

N H

1) HCl, MeOH reflux, 44%

O CO2Me

4

C23H26N2O5

2) ClCO2Me, Na2CO3 CH2Cl2, rt, 84%

OH

N

3) NaBH4, CeCl3 MeOH, 88% 4) MsCl, Et3N, DMAP CH2Cl2, 91% 5) Et3N, EtOH, H2O 60 °C, 83%

N MeO2C

CO2Me

1) MOMCl, i-Pr2NEt A 2) cat. t-BuOK 3) n-BuLi

Br

Br

Li-morpholineamide (2 eq) –78 °C, 1 h; isobutyraldehyde reflux, 1 h THF, 71%

Br

HO A, –78 °C, 2.5 h;

O Br

HCl/EtOH, 0 °C THF, 75%

5 OMe

N O

1) I2 (1.5 eq) collidine (1.5 eq) CH2Cl2, rt 84% (95:5) 2) NaN3, DMF 3) SnCl2, H2O; OMe Boc2O, Na2CO3 83% (2 steps)

Amino acid derivative

1) I2, EtOH-H2O 78% 2) Zn, THF 3) CH2N2 87% (2 steps)

NHBoc CO2Me

Fukuyama Group - Group Meeting Problems 11/13/2002 1

Ph N

O

Rh2(OAc)4 (1 mol%)

N

H

dichloroethane 130 °C

Ph

O

Ph

note: stereoselective

2 H

DMF, MeTi(Oi-Pr)3 c-HexMgBr

C11H19N decaline, 220 °C, 1 h 90%

THF, rt, 14 h 63%

3 3) triisopropylbenzene reflux, 5 h, 80%

1) NaNHNH2 ether-THF, 0 °C, 2 h N 2)

CN

HO

O

O

OH

HO

O

O

OH

N

MgSO4, EtOH, rt, 12 h (68% in 2 steps)

4 O

NO2 O S NH2 O

O2N

CN

Cl Et3N, THF reflux, 24 hr 76%

MeO

5 MeO

O

MeO

O

Me O Br

R Me OTIPS

MeLi (1 eq) THF, –100 °C;

MeO

A

TFAA, –78 °C; PhNH2, –15 °C 1) n-BuLi, THF, –78 °C; A, –78 °C; oxalic acid, H2O, rt 2) toluene, 110 °C; air, rt R=

Me MeO

O

R Me OTIPS

O OTBS

Me

Me O

N

NMe2

Fukuyama Group - Group Meeting Problems 11/20/2002 1 OMe OMe

Hg(OTf)2, THF rt, 30 min;

H N H

NaBH4, MeOH 0 °C to rt, 14 h

N3

47% (α:β = 2:1)

2 1)

O

3) NOClgas pyridine, –20 °C;

, hν quant.

reflux 85% in 2 steps

hν, pentane

2) n-BuLi 71%

O

4) TsOH benzene O

3 O H H

1) aq. NaOH PhH, reflux, 3 hr;

3) MCPBA, CH2Cl2 –78 °C, 30 min 66% (2 steps)

H

O CH2N2, Et2O 65-70% 2) tryptamine, MS4A Et2O, reflux, 24 hr

4

CO2Me

N

4) hν MeCN, quartz tube 6 hr, 60%

O

N H

H

O O

N3

O

BF3•OEt2

CO2Me SiMe2Ph

"tetrahydrofuran"

CH2Cl2 –50 °C

N3

SbCl5 CH2Cl2 –50 °C

HO

CO2Me Me

5 Bu 1) NH2OH•HCl Py-EtOH

Bu O

2) NaBH3CN MeOH, pH 3-4

N

toluene, reflux O

Fukuyama Group - Group Meeting Problems 11/27/2002 1

NaH; cat. CuCl acryloyl chloride A

HN toluene, rt, 23 h 56%

S O2

O

O

H

NO2

1) A, PhNCO Et3N, benzene rt, 48 h, 70%

3) LAH, ether rt, 20 h, 97% 4) NH2OSO3H (2 eq)

2) xs MeMgBr, THF –78 °C, 45 min; rt, 90 min, 72%

aq NaOH, CH2Cl2 0 °C, 75 min, 54% 5) cat. TsOH, benzene 60 °C, 48 h, 61%

O O

2 Ph NO2

N (4 eq) ,PhH; H

Py H N

CH3COCl

PhCHO (1 eq) 90%

O O (2 eq)

NC

hexane 90%

CN O N

3 48% HBF4

OMe O

Me OH O

OMe

MeNO2 91%

N2

4 Hept H

Sit-BuMe2 ·

Hept

NOBF4, CH3CN, –30 °C;

Me

N O

Br2, CCl4

Me

72%

5

Br

OMe

CO2Me

1) cat. Ti(Oi-Pr)4 EtMgBr (2 eq) 95% 2) TMSOTf 2,6-lutidine CH2Cl2, 88%

H

TiCl4

n-Bu3SnH cat. AIBN

CH2Cl2 –40 °C

benzene reflux

H

71%

95%

MeO

Br

O

OMe

Fukuyama Group - Group Meeting Problems 12/04/2002 1 OAc SMe N

O

OH

Me2S SMe BF4

OMe

reflux

bycyclic compound

O

N toluene O

2

O O

Ph

O

Ph

Ph2S2, AIBN Ph

PhCl, hν, reflux 52%

Ph

3 CpW(CO)3

O

O TfOH

OEt

Tungsten-contained ethyl ester

EtOH-CH2Cl2

OEt

O

1) (CO2H)2, 75% O 2) NOBF4, LiCl CH3CN, 47%

H

65%

4 COOH

HgCl2

O

LiPdCl3, CH3CN, 0 ºC to rt; A

CHCl

K2CO3, reflux 59%

23%

5 Cl (CH2O)n, AlCl3 (0.5 eq)

R

R R'

O

CH2Cl2, rt, 2 h; H2O 62%

R' O

Fukuyama Group - Group Meeting Problems 12/18/2002 1 O N2

1) TIPSOTf, i-Pr2NEt Et2O-Hex 0 °C to rt

TMSCHN2 CH2Cl2-Hex, rt; A

Cr(CO)5

1) MeO

OMe

MeO

OMe

1) TFA THF-H2O 85%

98%

MeO

O

SiO2, rt

2) hυ benzene

2

Sii-Pr3

O

NHt-Bu

Tricyclic compound

O 2) MeOH 100 °C 92%

2) t-BuNC THF 85%

MeO

3 S O2

4

Cl N

NaCH2S(O)CH3 NO2

Bu

CHO

THF-DMSO rt

Pd(PPh3)4 (1 mol%)

Bu N

THF, rt

Cl 85%

5 O MeHN

O

1) NCS, Et2O 2) cat CuCl, CuCl2 aq AcOH-THF

Me N

3) aq HCl, MeOH 4) toluene, reflux

O

OMe

Fukuyama Group - Group Meeting Problems 12/25/2002 1 MeO N MeO

1) Bu3SnTMS, CsF DMF, rt

2) PPA, 60 ºC 40 h, 66%

MeO H N MeO

8 h, 85%

OHC I

PPA=polyphosphic acid

2 O N Cl

O

NaN3 (ca. 5 eq)

O

O

MeCN/H2O (3:1) rt, 5 min

97%

3 1) BuLi ether, –20 °C;

N S

Me

SiMe3

S

MeO

CH2Br

2) MeOTf benzene, 0 °C 96%

Me Me

3) CsF DMSO, rt; aqNaOH, 68%

CH2SMe

MeO

58%

4 N3 HO

H

HO

O

OH

Bn2NH, AcOH

Pd(OH)2/C, H2

EtOH, 40 °C

MeOH

HO

HO

OH

5 O

O (TMS)3SiH Me AIBN H N3

H H N

NH

NH2 OH