Direct Access to 2,3,4,6-Tetrasubstituted Tetrahydro‑2<i>H</i>‑pyrans via Tandem S_N2′–Prins Cyclization

A new, direct, and diastereoselective synthesis of activated 2,3,4,6-tetrasubstituted tetrahydro-2<i>H</i>-pyrans is described. In this reaction, iron­(III) catalyzed an S_N2′–Prins cyclization tandem process leading to the creation of three new stereocenters in one single step. These activated tetrahydro-2<i>H</i>-pyran units are easily derivatizable through CuAAC conjugations in order to generate multifunctionalized complex molecules. DFT calculations support the in situ S_N2′ reaction as a preliminary step in the Prins cyclization