Page 17 - Demo-1

Dynamic Kinetic Resolution: A Powerful Approach to Asymmetric Synthesis
OH
98% yield 98% de, 99% ee
OH
MeO
MeO
CO2Et
CO2Et
Rhizopus arrhizus
Baker's yeast
O
Ru(II)(R)-BINAP MeO H2
Ru(II)(S)-BINAP MeO H2
OH
100% yield 97% de, 96% ee
OH
93% yield 93% de, 86% ee
CO2Et
CO2Et
MeO
CO2Et
70% yield 98% de, 95% ee
Erik Alexanian Supergroup Meeting March 30, 2005
For leading references, see: Pellissier, H. Tetrahedron 2003, 59, 8291
Pamies, O.; Backvall, J.-E. Chem. Rev. 2003, 103, 3247
Methods for Asymmetric Synthesis
Synthesis utilizing existing stereogenic centers (chiral substrates or auxiliaries) Catalytic enantioselective organic reactions
- Chemocatalysis - metal-mediated, Lewis acid-mediated, organocatalysis - Biocatalysis - enzymes (hydrolases)
Resolution
- Conventional separation procedures - Kinetic resolution
S kR P RR
S kS P SS
Problems associated with standard kinetic resolutions: - Theoretical yield = 50%
% ee
100
50
0 0
E = kfast/kslow = 10
ee S
ee P
50 100
- Separation of product from remaining substrate required
- In the majority of processes, only one stereoisomer is desired - Drop in enantiomeric purity as process nears 50% conversion
% conversion