Enantioselective Synthesis of (–)-Stemoamide

Dedicated to Professor Guo-Qiang Lin on the occasion of his 70^th birthday

Abstract

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.

Key words

carbonylation - biomimetic synthesis - asymmetric transfer hydrogenation - iminium ion cyclization - stemoamide

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