Stereoselective Synthesis of C ‐2‐Methylene and C ‐2‐Methyl α‐ and β‐ C ‐Glycosides from 2‐ C ‐Branched Glycals: Formal Total Synthesis of (–)‐Brevisamide

The stereoselective synthesis of deoxy C ‐glycoside derivatives that have a methylene or methyl group at C ‐2 position was investigated by employing the Claisen rearrangement of 2‐vinyloxy methyldeoxy‐glycals as the synthetic precursors. The method proceeded with high diastereoselectivity to afford C ‐2‐methylene α‐ C ‐glycosides. Complementary to this protocol, a Zn II ‐mediated anomerization of the α‐ C ‐glycosides to give the corresponding β‐ C ‐glycosides was also used to obtain diastereomerically pure C ‐2‐methylene β‐ C ‐glycosides. The generality of the reaction was fully evaluated, and the developed method was successfully applied to the formal stereoselective total synthesis of (–)‐brevisamide, a monocyclic ether alkaloid that was isolated from Karenia brevis (red tide dinoflagellate).