Rapid and Scalable Photocatalytic C(sp2)–C(sp3) Suzuki−Miyaura Cross-Coupling of Aryl Bromides with Alkyl Boranes

Abstract

In recent years, there has been a growing demand for drug design approaches that incorporate a higher number of sp3-hybridized carbons, necessitating the development of innovative cross-coupling strategies to reliably introduce aliphatic fragments. Here, we present a novel and powerful approach for the light-mediated B-alkyl Suzuki−Miyaura cross-coupling between alkyl boranes and aryl bromides. Alkyl boranes can be easily generated via hydroboration from readily available alkenes, exhibiting excellent regioselectivity and enabling the selective transfer of a diverse range of primary alkyl fragments onto the arene ring. This methodology eliminates the need for expensive catalytic systems and sensitive organometallic compounds, operating efficiently at room temperature within just 30 minutes. Interestingly, our mechanistic studies reveal an unexpected mechanistic scenario that operates through transmetalation rather than alkyl radical formation, setting it apart from established metallaphotoredox protocols. Moreover, we demonstrate the advantageous translation of the present protocol to continuous-flow conditions, enhancing scalability, safety, and overall efficiency of the method. This versatile approach offers significant potential for accelerating drug discovery efforts by enabling the introduction of complex aliphatic fragments in a straightforward and reliable manner.