Total Synthesis of (<i>R</i>)-Sarkomycin Methyl Ester via Regioselective Intermolecular Pauson–Khand Reaction and Iridium-Catalyzed Asymmetric Isomerization

Abstract

A new five-step enantioselective synthesis of ( R)-sarkomycin methyl ester is described. The cyclopentane scaffold was built by a regioselective intermolecular Pauson-Khand reaction. Enantioselectivity was introduced by a novel Ir-catalyzed isomerization reaction. The last steps involved a catalytic hydrogenation of the exocylic double bond, followed by the deprotection and elimination of the amino group. This route is the shortest enantioselective synthesis of this antibiotic reported to date.