Prins Reaction of Homoallenyl Alcohols: Access to Substituted Pyrans in the Halichondrin Series.

Prins reaction of homoallenyl alcohols with aldehyde dimethylacetals in the presence of methoxyacetic acid directly affords tetrasubstituted pyrans relevant to halichondrins with complete control of the C27 stereogenic center. Regioselective Tsuji reduction of the resultant allylic acetates stereoselectively establishes the C25 stereogenic center and C26 exocyclic olefin. Building upon these findings, we achieved concise access to the halichondrin C14-C38 and eribulin C14-C35 fragments.