Enantioselective Synthesis of ABCF Tetracyclic Framework of <i>Daphniphyllum</i> Alkaloid Calyciphylline N

Abstract

Efforts toward the enantioselective synthesis of Daphniphyllum alkaloid calyciphylline N which leads to efficient preparation of the ABCF tetracyclic framework containing three bridgehead all-carbon quaternary stereocenters are described. This synthetic work features the utilization of an asymmetric conjugate addition to install the C5 all-carbon quaternary center, an efficient successive inter/intramolecular aldol sequence to build the critical bicyclo[2.2.2]octanone BC core, and a ring closing metathesis reaction followed by stereoselective Nagata conjugate cyanation to deliver the functionalized F ring.