The first transannular [4+3] cycloaddition reaction: synthesis of the ABCD ring structure of cortistatins

A 14-membered macrocycle with an allene and a furan strategically located at across the ring from each other is synthesized using an allene ring closing metathesis reaction. Upon treatment of the macrocycle with a catalytic amount of Pd(OAc)2 and other additives, the first transannular [4+3] cycloaddition occurred to yield 37% of a tetracyclic compound containing the ABCD ring structure of the natural products cortistatins.

Graphical abstractA 14-membered macrocycle with an allene and a furan is synthesized using an allene ring closing metathesis reaction. Upon treatment of the macrocycle with a catalytic amount of Pd(OAc)2, the first transannular [4+3] cycloaddition occurred to yield 37% of a tetracyclic compound containing the ABCD ring structure of the natural products cortistatins.Figure optionsDownload full-size imageDownload as PowerPoint slide