Direct Access to 2,3,4,6-Tetrasubstituted Tetrahydro-2H-pyrans via Tandem SN2'-Prins Cyclization

Abstract

A new direct and diastereoselective synthesis of activated 2,3,4,6-tetrasubstituted tetrahydro-2H-pyrans is described. In this reaction iron(III) catalyzed an SN2’-Prins cyclization tandem process leading to the creation of three new stereocenters in one single step. These activated tetrahydro-2H-pyran units are easily derivatizable through CuAAC conjugations in order to generate multi-functionalized complex molecules. DFT calculations support the in situ SN2’ reaction as a preliminary step in the Prins cyclization