Stereocontrolled Synthesis of Highly Substituted Tetrahydropyrans

Significance

A Re(VII) complex catalyzed the highly selective condensation of easily accessible starting materials using a very mild and simple protocol to give densely functionalized tetrahydropyrans 3 (THP). Aromatic aldehyde partners 2 give a single diastereomer where all substituents are equatorially oriented. Whereas aliphatic aldehydes give diastereomeric mixtures (4 and 5), ­alkenyl aldehydes provide an alternative, as illustrated by complex THP 11. Achieving high atom-efficiency, the catalytic Prins cyclization reported improves previous protocols using excess acid (the conjugate base moiety is generally incorporated into the THP at the end of the reaction).