Total Syntheses of Hosieines A-C

Abstract

The collective total syntheses of (±)-hosieines A-C with a cage-like tetracyclic framework have been realized, which includes the first syntheses of hosieines B-C. The key strategy of the synthesis employs a one-pot domino reaction that involves Cu-catalyzed [3+2] cycloaddition, 1,6-enone formation, and 1,6-aza-Michael addition forming the 5/6/6-aza-tricyclic skeleton. Other salient synthetic tactics comprise a challenging double bond migration and a 1,4-aza-Michael addition reaction to afford the tetracyclic framework.

Keywords: [3+2] reaction; alkaloids; natural products; one pot; total synthesis.