Regulation of diastereoselectivity through the epimerisation of a cyclic intermediate in the reaction of cyclic ketene ortho ester with aldehydes

Abstract

A highly stereocontrolled synthesis of 3 was accomplished. This involves the conversion of the cyclic intermediate 5 (from the reaction of dihydropyran 1 with aldehyde promoted by Lewis acid catalyst) to 6 in the presence of bases and introduction of an ester functionality from hydrolysis of the ortho ester intermediate. The method described herein is successful with a variety of aldehydes and affords products in high yields (55–89%) with useful levels of diastereoselectivity (10–30∶1). Experiments are described which unambiguously established the stereochemistry for the coupling products. Synthetic manipulations of products by functional group transformations to useful compounds are also reported.