Enantioselective construction of cis-2,6-disubstituted dihydropyrans: total synthesis of (-)-centrolobine

Abstract

This paper presents a simple and efficient route to chiral cis-6-substituted 2-(2-hydroxyethyl)-5,6-dihydro-2H-pyrans, a versatile chiral building block. The strategy is based on three key transformations: enantioselective hetero-Diels-Alder (HDA) reaction of aldehyde with Danishefsky's diene, selective reduction of carbonyl function, and Claisen or related rearrangement. The synthetic utility of the methodology is illustrated by total synthesis of antibiotic (-)-centolobine.