X=Y–ZH systems as potential 1,3-dipoles. Part 55: Cascade 1,3-azaprotio cyclotransfer–cycloaddition reactions between ketoximes and divinyl ketone

Abstract

The cascade 1,3-azaprotio cyclotransfer–1,3-dipolar cycloaddition reaction between ketoximes and divinyl ketone [or its equivalent bis(2-chloroethyl) ketone] affords high yields of substituted 1-aza-7-oxabicyclo[3.2.1]octan-4-ones and 1-aza-8-oxabicyclo[3.2.1]octan-4-ones where the cycloaddition regioselectivity is controlled by a judicious choice of experimental conditions. The N–O bonds in the products are reductively cleaved to form piperidones and perhydroazepinones and the ketone moiety undergoes stereoselective sodium cyanoborohydride reduction to afford anti-1-aza-7-oxa-4-hydroxybicyclo[3.2.1]octanes and anti-1-aza-8-oxa-4-hydroxybicyclo[3.2.1]octanes.