Electrocyclic Ring-Opening/π-Allyl Cation Cyclization Reaction Sequences Involving <i>g</i><i>em</i>-Dihalocyclopropanes as Substrates:  Application to Syntheses of (±)-, (+)-, and (−)-γ-Lycorane

Abstract

The readily prepared gem-dibromocyclopropanes (±)-13 and (±)-19 each engage in a silver(I)-promoted electrocyclic ring-opening/π-allyl cation cyclization sequence to deliver the hexahydroindole (±)-20, which participates in a Suzuki cross-coupling reaction with arylboronic acid 3 to give the tetracyclic compound (±)-21. Catalytic hydrogenation of this last compound proceeds in a completely stereoselective manner to give the saturated analogue (±)-24, which undergoes Bischler-Napieralski cyclization on reaction with phosphorus oxychloride. The resulting lactam (±)-25 is then reduced with lithium aluminum hydride to give (±)-γ-lycorane [(±)-1]. By using (−)-menthyl-derived carbamates 27 and 28, this chemistry has been extended to the synthesis of the (+)- and (−)-modifications of the title compound.