Page 8 - Demo-1

Chemical Dynamic Kinetic Resolution: Noyori Reductions ! Noyori !-keto ester reductions describe relative rates
OO
2
kinv
OO MeO Me
NHCOPh
0.4 mol% (R)-BINAP-Ru(II)
H2, CH2Cl2
kfast
0.4 mol% (R)-BINAP-Ru(II)
H2, CH2Cl2
kslow
O OH
2
O OH
2
MeO
3 Me NHCOPh
MeO
MeO
3 Me NHCOPh
94% de (93% ee)
uO
O
3 Me NHCOPh
kfast/kslow = 15 kinv/kfast = 6.1 kinv/kslow = 92
Noyori, Bull. Chem. Soc. Jpn., 1995, 68, 36. "The absolute configuration at C-3 is governed by the handedness of the BINAP ligand while the C-2 configuration is dependent on
substrate structures."
X P
P R OH O OMe 2
Noyori, JACS, 1989, 111, 9135.
PX
P Ru O O H
OH O
OMe HN Me
syn O
Me
Me
HH 3OMe ON H
Me
anti
Me H O
Chemical Dynamic Kinetic Resolution: Noyori Reductions computations predict relative rates of reactions of enantiomers
! Chiral Ru(II) complex catalyzes benzil reduction Ts
Ph
N
O
Ph H2 Ph O
OH
Ru Ph PhNCl
Ph
OH
100% yield >99% ee
chiral : meso = 9: 1
HCOOH, Et3N
OH
Ph
kfast
OH
Ph
kinv
Ph
O OH
Ph
O
Ph Ph
O
Computational modelling indicates that kfast/kslow = 55
OH k OH
slow
Ph Ph Ph Ph
O OH
Noyori, Org. Lett., 1999, 1, 1119.