Unanticipated Bicyclic Etherification in Luche Reduction: Asymmetric Total Syntheses of Diospongins A and B and Tetraketide.

In the synthesis of diospongin B based on rearrangement of δ-hydroxyalkynone to 2,3-dihydro-4 H -pyran-4-one, we discovered an unanticipated beguiling reaction giving a thermodynamically less stable 4-hydroxy-2,6- trans -disubstituted-THP moiety via bicyclic etherification under Luche reduction conditions and simple acid hydrolysis. The practical applicability of this method is exemplified by the asymmetric total syntheses of diospongins A and B, several analogues, and tetraketide.