A general approach to high-yielding asymmetric synthesis of chiral 3-alkyl-4-nitromethylchromans via cascade Barbas-Michael and acetalization reactions

Abstract

A general approach to the high-yielding asymmetric synthesis of chiral 3-alkyl-4-nitromethylchromans as drug intermediates was achieved through cascade Barbas-Michael and acetalization (BMA) reactions on 2-(2-nitrovinyl)phenols with aldehydes in the presence of a catalytic amount of (R)-DPPOTMS and PhCO2H. Herein, we have also demonstrated the application of chiral BMA products in the synthesis of functionalized chromanes and chromenes in very good yields with high optical purity, which are very useful compounds in medicinal chemistry. © 2011 The Royal Society of Chemistry.