Fukuyama Group - Group Meeting Problems
06/02/2007
1) MeLi, Et2O;
MeI;
pyrrolidine, Et2O
86%1
Cr(CO)63) MsCl, Et3N,0 °C

IncludingCr4) NaOH, EtOH
2) n-BuLi, –78 °C;
70% (3 steps)
MeCHO, –78 °C
1) LDA, THF
MeO2C
Burgess rgt. (3 eq.)
–78 °C;NH
4-NO2 C6H4CHO

O

THF

74%

4-NO2C6H425%
A. Papagni et al., Eur. J. Org. Chem., 1149 (2001)

O
HN
H

NH2OH
R2N
EtO2C
FO

Cl

MeCN

N

NR2 =A

ClOClO

CO2EtO(COCl)2, DMF (cat.)
DCE, 40 min;evaporation;

ZnBr2 (cat.)i-Pr2NH

A, DCE, 2 h;
H2O, overnightCH2Cl235 min

N2R2N
EtO2C
F

CO2Et

M. M. Bio, et al., Synthesis, 19 (2005)

3MeBrMgO
Me

CO2MeMeCl

PPh3 (2.5 eq.)
CCl4 (3.0 eq.)
DBU (3.0 eq.)

2MeOBnCHO(2 eq)(Cp)2TiCl2

LDA

THF
–40 °C to rt

THF–78 °C

51%

81%

Me41) LDA, HMPA
THF, −78 °C;
TMSCl, to 0 °C;
HCl, H2O, 74%

1) Ac2O
Et3N, DMAP
CH2Cl2rt[Rh(CO)2Cl]2(0.5 mol%)
C25H36O2) NaCN
DMSO
130 °C
51% (2 steps)

toluene110 °CMeHOBnP. A. Wender et al., Org. Lett., 2, 2323 (2000)
Me1) TBSCl, imidazole
DMF, 97%2) s-BuLi, PPh3CH3Br 2) Red-Al, Et2O
THF, −78 °C to 0 °C
0 °C; −78 °C
85%NIS, 97%
R = (CH2)3CH(OCH2CH2O)

2) PPh3, Ag2CO3
Pd(OAc)2, 65 °C;
TBAF, THF
90 %O

Me93%1) TBAF, THF
quantRMeOTIPSMeHROH

L. E. Overman et al., J. Am. Chem. Soc., 121, 5467 (1999)

51) SmI2
MeOH-THF

CHOO

CO2Et

2) TBSCl, ImDMF

threestereocenters1) LiOH, MeOH
2) i-BuO2CCl
Et3N, Et2O;
CH2N23) Cu(CF3COCHCOCF3)2(5 mol%)
CH2Cl2, reflux

OHO
H

OTBS

J. S. Clark et al., Angew. Chem. Int. Ed., 46, 437 (2007)

Fukuyama Group - Group Meeting Problems
06/06/2007
1HNBuN

1) NCS, CH2Cl2, 0 °CBu2) cat. CuCl, THF, 50 °C
58% (2 steps)

ClR. Göttlich, Synthesis, 1561 (2000)

2MeMeHOH
Me1) KOt-Bu, 18-c-6THF, 0 ºC; MeI
98%2) p-TsOH
acetone/H2O, reflux
74%OMeMeOMeH

tetracycliccompound1) LAH
Et2O, 0 ºC
79%2) MsCl, Et3N
CH2Cl279%3) KOt-Bu
t-BuOH, 40 ºC
84%H O MeMeMeOMeMeH

H
MeL. A. Paquette et al., J. Org. Chem., 64, 3244 (1999)

3O
H1)
SO2Ph
O

H
OO

(C10H8O2)

t-BuOLi, THF, –78 °C

C18H10O42) DDQ, benzene, reflux
O1,2-dichlorobenzenereflux
83% for 3 stepsOO
C17H10O3D. Mal et al., Chem. Commun., 1181 (1996)

4OMe
OMe

O

CH2=S(O)Me2
THF
0 ºC
96%

1) 28% NH3 (aq.)
dioxanesealed tube
120 ºC
2) HONO (aq.)
0 ºC to rt
77% (2 steps)

1) Jones reagent
acetone2) CH2N2, Et2O
0 ºC, 84%
C11H16O33) hυbenzene, 96%
4) DBU, THF
reflux, 96%HO

MeO2C H

N-C. Chang et al., J. Org. Chem., 58, 4756 (1993)

Fukuyama Group - Group Meeting Problems
06/09/2007
11) KCN (6.0 eq)
Boc2O (3.0 eq)
CH2Cl2-H2O
15 h, 96%OMe

MeON

MeO

TosMIC (1.0 eq)
K2CO3 (1.0 eq)
MeOH
reflux, 1 h;
KOH, reflux, 6 h2) DIBAL
toluene–78 °C, 3 h63%

C14H13NO3OMe
tricycliccompound
C22H24N2O6 o-dichlorobenzene
reflux, 20 h

MeONMeOO

90%

82%
J. K. Cha et al., J. Am. Chem. Soc., 123, 3243 (2001)21) NH2OH·HCl
NaOH
EtOH-H2OO

A(C6H10ClNO)

2) Cl2, CH2Cl2
78% (2 steps)

n-C7H15XPOOO

NaHMDS
THF, –78 °C;

XP =N
SO21) NaBH3CN, MeOH
2) NaH, toluene, reflux;
n-BuLi, CeCl3–78 oC to rt
59% (2 steps)

A;
1N HCl aq.
64%n-Bun-C7H15N
H

W. Oppolzer et al., Tetrahedron Lett., 35, 7015 (1994)

3OS

MeO
MeO

NO
Et

Ac2O, TsOH

O

toluene

O

70%

MeO2C

CO2Me

MeO

NO

MeO

A. Padwa et al., J. Org. Chem., 61, 4888 (1996)41) DMF, POCl3
CH2Cl2, 0 °C to rt

OPh

Me

2) NaN3, DMF, rt3) hv (Pyrex filter)
MeCN, rtmonocyclic
compound
C9H7NO

1) Ph3P, toluene
reflux94% (E/Z = 92/8)

CO2Me
CO2Me2) DMAD, toluene
reflux, 55%N

Ph

T. Nakata et al., Heterocycles, 48, 2551 (1998)

5OClBrSMe1) hexamethylenetetramine
CHCl3, rt2) conc. HCl, EtOH, rt(acidic workup)4) NaIO4 (1 eq)
MeOH-H2O, rt
89%3) 2,5-dimethoxytetrahydrofuran
NaOAc, AcOH, 100 °C
75% (3 steps)

5) TFAA
DMF, 0 °C
42%O
ClNS

V. Nacci et al., J. Med. Chem., 41, 3763 (1998)

Fukuyama Group - Group Meeting Problems
06/23/2007
1O1)
Ba(OH)2
wet THF
rt, 86%OHNTrO

MeOOEtP(OEt)2MeO

C13H19NO22) TFA
Et3SiHCH2Cl20 oC, 71%NH21) Ac2O, Et3N, CH2Cl2

TsOH (10 mol%)

2) LHMDS, toluene,–78 to 80 oC
77% (2 steps)3) DIBAL, toluene,–78 oC, 59%

toluenereflux

MeO
MeO

N
HONH

N. A. Magomedov et al., J. Org. Chem. 72, 3808 (2007)

2
Me2C NNHCO2MePb(OAc)4A

MeOH

C6H12N2O3

MeO
O

40-80%

CO2HN
MeN

MeO

1) DPPA, TEA

A*2) toluene, reflux

toluene, reflux

OMe

MeO

*Theoretically: 2.0 eq
N
Me75%J. Warkentin, Synthesis, 279 (1970)
James H. Rigby, Patrick J. Burke, Heterocycles, 67, 643 (2007)

3MeHO
MeH

LiTMP (1.0 eq)*, TMSCl (1.0 eq)*
THF, –78 to 0 ºC;
Pd(OAc)2 (0.5 eq), CH3CN

TBSO
O* theoretical amount

68% (2 steps)

6N NaOH (4.0 eq)
aq. H2O2 (3.0 eq),
MeOH, 0 ºC, 83%;

H

MeLi, NH3, THF, –33 ºC, 63%;
aq. HF/CH3CN (5:95 v/v)
86%

O
MeOH

O

OH

S. J. Danishefsky et al., Angew. Chem. Int. Ed., 46, 2199 (2007)

4OH1) SeO2, TBHP, CH2Cl2, 90%2) NaH, AllylBr (theoretically 1 equiv)
THF, 73%OO3) DBU, toluene, 220 °C, 75%4) TPAP, NMO (theoretically 1 equiv)
MS4A, CH2Cl2, 70%
L. Barriault et al., Org. Lett., 4, 1371 (2002)

5CONEt2
2

OTBS

1) Jones' reagent, acetone, 0 °C, 96%
2) SOCl2, CH2Cl2, 0 °C to rt; evaporation;
PhNHCH(Me)CO2Me, toluene, 89%3) LiOH·H2O, THF-H2O, reflux, 99%
4) DCC, CH2Cl2, 89%PhN

MeCONEt2

G. Bélanger et al., J. Org. Chem., 72, 1104 (2007)