CoMFA Study of Chiral Catalysts

Abstract

A QSAR using Comparative Molecular Field Analysis (CoMFA) is developed for a set of 23 catalysts containing bis-oxazoline or phosphino-oxazoline ligands that are known to induce asymmetry during the Diels-Alder reaction of N-2-alkenoyl-1, 3-oxazolidine-2-one with cyclopentadiene. It is shown that extemely high q2 statistics can be derived using standard modeling protocols when internal validation alone is done as well as when an external test set is used. From these models it is shown that approximately 70% of the variance in the observed enantiomeric excess can be attributed to the steric field and the remainder of the variance to the electrostatic field. Suggestions about how to improve the performance of inefficient catalysts are given the thesis.