Enantioselective Synthesis of (-)-Stemoamide

An enantioselective synthesis of (-)-stemoamide is presented. Noyori's ruthenium complex catalyzed asymmetric transfer hydrogenation of an alkynone delivered the (S)-C8 stereogenic center in 97.7% ee. An iron(III) chloride promoted and bioinspired N-iminium ion cyclization afforded a 3: 1 ratio of two diastereomers in favor of the cis-isomer. The diastereomeric ratio was enriched to 50: 1 by a silver-catalyzed cycloisomerization. The subsequent dynamic ruthenium-catalyzed CO-insertion reaction secured an enantioselective total synthesis of (-)-stemoamide in 18% overall yield with high optical purity.