The Size-Accelerated Kinetic Resolution of Secondary Alcohols.

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-π-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.

Size-dependent rate acceleration in the silylation of secondary alcohols: the bigger the faster.

Relative rates for the reaction of secondary alcohols carrying large aromatic moieties with silyl chlorides carrying equally large substituents have been determined in organic solvents. Introducing thoroughly matching pairs of big dispersion energy donor (DED) groups enhanced rate constants up to four times, notably depending on the hydrogen bond donor ability of the solvent. A linear correlation between computed dispersion energy contributions to the stability of the silyl ether products and experimental relative rate constants was found. These results indicate a cooperation between solvophobic effects and DED-groups in the kinetic control of silylation reactions.