The design of novel N-4'-pyridinyl-alpha-methyl proline derivatives as potent catalysts for the kinetic resolution of alcohols.
A novel family of chiral acylation catalysts based on a N-4'-pyridinyl-alpha-methyl proline structure has been studied. A set of 31 compounds has been easily prepared and screened in the kinetic resolution of racemic alcohol 33 resulting in high enantioselectivities in most cases. From results obtained, H-bonding interactions between the catalyst and the substrate would appear essential to afford high enantioselectivity during the catalytic acylation. Additional solvent dependence and anhydride studies have been made to better identify the mechanism. This work has been further extended to the study of a number of structurally different alcohols. Ethanolamine derivatives in particular were found to be highly effective substrates (up to S = 18.8) in the kinetic resolution.
Priem
Ghislaine
G
GlaxoSmithKline, Medicines Research Centre, Medicinal Chemistry, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, United Kingdom.
Pelotier
Béatrice
B
Macdonald
Simon J F
SJ
Anson
Mike S
MS
Campbell
Ian B
IB
D000215:Acylation; D000438:Alcohols / Q000737:chemistry*; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D020650:Combinatorial Chemistry Techniques; D004983:Ethanolamines / Q000737:chemistry*; D006860:Hydrogen Bonding; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011392:Proline / Q000031:analogs & derivatives* / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*; D013237:Stereoisomerism
D000438:Alcohols; D004983:Ethanolamines; D011725:Pyridines; D011392:Proline