Highly Enantioselective Formal Synthesis of (+)-Treprostinil Enabled by Rhodium-Catalyzed Enyne Cycloisomerization

Abstract

Herein, a highly enantioselective formal synthesis of (+)-Treprostinil via the interphenylene prostaglandin E₁ scaffold was described. The chiral multi-substituted cyclopentanone was constructed via a [Rh(Duanphos)SbF₆-catalyzed asymmetric enyne cycloisomerization and a copper hydride-mediated conjugate reduction. In addition, a new type of interphenylene prostaglandin scaffold was obtained via a formal Alder-ene reaction in high yield with excellent chemoselectivity.