Organocatalytic asymmetric cross-aldol reaction of 2-chloroethoxy acetaldehyde: diversity-oriented synthesis of chiral substituted 1,4-dioxanes and morpholines

Abstract

Herein we report a facile organocatalytic asymmetric direct cross-aldol reaction of 2-chloroethoxy acetaldehyde with aromatic aldehydes using (S)-(−)-α,α-diphenyl-2-pyrrolidinemethanol as an organocatalyst to afford anti-2-(2-chloroethoxy)-1-arylpropane-1,3-diols with excellent enantioselectivities (95–98%) and moderate diastereoselectivities (3.5–7:1). The 1,3-diols, obtained after the aldehyde reduction, represent highly functional intermediates that allow for further diversification into both chiral 1,4-dioxanes and morpholines, compounds that frequently display interesting biological activities.