Synthesis of phytuberin. 4-endo-tet acid-catalyzed cyclization of alpha-hydroxy epoxides.

The total synthesis of phytuberin, a phytoalexin of the Solanum genus, from (-)-alpha-santonin is reported. The key steps include (a) reductive cleavage of the C-O bond of the gamma-lactone with concomitant protection of the C1 double bond, (b) Sharpless stereocontrolled hydroxy-assisted epoxidation of allylic alcohol 6 and simultaneous deprotection of the C1 double bond, (c) a rare 4-endo-tet acid-catalyzed cyclization of an alpha-hydroxy epoxide, and (d) an unprecedented 4-exo selenocyclization of a homoallylic alcohol.