Profiling and Application of Photoredox C(sp3)-C(sp2) Cross-Coupling in Medicinal Chemistry

ACS Med Chem Lett. 2018 May 7;9(7):773-777. doi: 10.1021/acsmedchemlett.8b00183. eCollection 2018 Jul 12.

Abstract

Recent visible-light photoredox catalyzed C(sp3)-C(sp2) cross-coupling provides a novel transformation to potentially enable the synthesis of medicinal chemistry targets. Here, we report a profiling study of photocatalytic C(sp3)-C(sp2) cross-coupling, both decarboxylative coupling and cross-electrophile coupling, with 18 pharmaceutically relevant aryl halides by using either Kessil lamp or our newly developed integrated photoreactor. Integrated photoreactor accelerates reaction rate and improves reaction success rate. Cross-electrophile coupling gives higher success rate with broad substrate scope on alkyl halides than that of the decarboxylative coupling. In addition, a successful application example on a discovery program demonstrates the efficient synthesis of medicinal chemistry targets via photocatalytic C(sp3)-C(sp2) cross-coupling by using our integrated photoreactor.