Two Csp³−Csp² and Csp³−H bonds are formed on the same carbon atom by reacting the tosylhydrazone of chiral Uhle's ketone with 2,2-dimethylethenylboronic acid. This metal-free reductive coupling afforded an unexplored disconnection for the asymmetric synthesis of (−)-6,7-secoagroclavine.

Abstract

A concise, convergent, and enantioselective synthesis of (−)-6,7-secoagroclavine, a pivotal intermediate in the synthesis of both clavine and ergot alkaloids, was accomplished from a derivative of the renowned Uhle's ketone. The synthesis is centered on metal-free reductive coupling of the tosylhydrazone derivative of protected 4-amino Uhle's ketone and commercially available 2,2-dimethylethenylboronic acid, which is used as a four-carbon building block. This novel approach directly sets the stereochemistry on the difficult-to-access aryl vinyl methane carbon stereogenic center of (−)-6,7-secoagroclavine.