106
H. Zhu et al.
N
Boc
O
O
F8
1) TFA
2) PhI(OOCCF
3 )
2 , 2,6-lutidine,
4 Å MS, 90% (two steps)
N
O
O
F24
1) 1,3-diaminopropane,
CF
3 CH
2 OH, Et
2 O
2) KOH, I
2 ,
96% (two steps)
N
H
OH
F25
O
CO
2 Me
N
H
O
O
CO
2 Me
O
N
H O
O
CHO
O
P(O)(OEt)
2
HN
O
O
O
HN
O
O
F29
OAc
HN
O
OH
26 (L-696,474)
OAc
1) dimethyldioxirane, 95%
2) Dess-Martin, NaHCO
3.
1)
B33, KHMDS,
86% (two steps)
2) (CH
3 O)
2 POCH
2 Li
3) TBAF, AcOH, 81%
(two steps)
4) Dess-Martin,
NaHCO
3
NaOCH
2 CF
3 , CF
3 CH
2 OH,
52% (two steps, 5:1
mixture of diastereomers)
1) CeCl
3 , NaBH
4
2) Ac
2 O, pyridine,
86% (two steps)
MgSO
4 , 77%
F26
F27
F28
N
H
OH
O
I
OBn
OBn
TBDPSO
S
TBDPSO
N
N
N
N
Ph
1) LDA, LiCl,
2-benzyloxy-1-iodoethane,
94%
2) LiH
2 NBH
3 , 88%
3) PPh
3 , I
2 , imidazole, 89%
1) LDA. LiCl;
2) LiH
2 NBH
3 ,
91% (two steps)
3) TBDPSCl, Et
3 N,
dimethylaminopyridine,
89%
1) H
2 , Pd(OH)
2 /C,
2) 1-phenyl -1
H-tetrazole -5
-thiol,
DEAD, 86% (two steps)
3)
m-CPBA, NaHCO
3 , 97%
O O
F30
F33
F31
F32
A
B
Scheme 9 Synthesis of L-696,474 and intermediate F33