The Size-Accelerated Kinetic Resolution of Secondary Alcohols.

ABSTRACT: The factors responsible for the kinetic resolution of alcohols by chiral pyridine derivatives have been elucidated by measurements of relative rates for a set of substrates with systematically growing aromatic side chains using accurate competitive linear regression analysis. Increasing the side chain size from phenyl to pyrenyl results in a rate acceleration of more than 40 for the major enantiomer. Based on this observation a new catalyst with increased steric bulk has been designed that gives enantioselectivity values of up to s = 250. Extensive conformational analysis of the relevant transition states indicates that alcohol attack to the more crowded side of the acyl-catalyst intermediate is favoured due to stabilizing CH-?-stacking interactions. Experimental and theoretical results imply that enantioselectivity enhancements result from accelerating the transformation of the major enantiomer through attractive non-covalent interactions (NCIs) rather than retarding the transformation of the minor isomer through repulsive steric forces.

SUBMITTER: Zipse H 

PROVIDER: S-EPMC7821155 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature