Page 9 - Demo-1

Chemical Dynamic Kinetic Resolution: Ru(II) Reductions in Synthesis
! Formal synthesis of (—)-Balanol 1 proceeds through (2S,3R)-3-hydroxysilane 2. HO
O HO
OH
O
N H
1
COOH
OH
H2N
OH
COOH
O
O
NH2
2
HN
! Ru(II) catalyzed DKR provides key step in synthesis of 2.
O H2 OH
100% yield > 99% ee > 98% de
PhthN
COOMe Ru-[(R)-MeO-BIPHEP] PhthN (0.5 mol% catalyst)
COOMe
NHAc
O
1. 10 mol% CuCl/(S)-p-tol-BINAP NaOt-Bu (1.7 eq)
t-BuOH (5.0 eq) PMHS (2.2 eq)
toluene, 26 h 2. TBAF
O Me
NHAc CH Cl 22
Chemical Dynamic Kinetic Resolution: Conjugate Reduction racemization of starting material induced by added base
Genet, Tet. Lett., 1998, 39, 6467.
89% yield
91 : 9 syn : anti
91% ee
Me
Ph
Ph
! Product trapped as enol silane to prevent epimerization
O OSiR3 O
R [H] R F— R
A variety of alkyl, aryl substituents
at positions 3 and 5 are tolerated
Buchwald, JACS, 2002, 124, 2892.
kfast/kslow = 25-52
krac
"very fast"
kfast "fast"
R1 R1 R1
NaOtBu/ tBuOH
O
R [H] R F— R
kslow "slow"
R1 R1 R1
OSiR3 O
Without base, a classical KR is observed; choice of base is crucial for DKR.