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
Tài liệu chuẩn tham khảo Phát triển kênh bởi Ths Nguyễn Thanh Tú Đơn vị tài trợ / phát hành / chia sẻ học thuật : Nguyen Thanh Tu Group Hỗ trợ trực tuyến Fb www.facebook.com/DayKemQuyNhon Mobi/Zalo 0905779594
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