A General Copper Catalytic System for Suzuki-Miyaura Cross-Coupling of Unactivated Secondary and Primary Alkyl Halides with Arylborons.

Abstract

Suzuki-Miyaura cross-couplings (SMC) are powerful tools for the construction of carbon-carbon bonds. However, the couplings of sp3-hybridized alkyl halides with arylborons often encounter several problematic issues such as sluggish oxidation addition of alkyl halides and competitive β-hydride elimination side pathways of metal-alkyl species. In precedent reports, copper is mainly utilized for the coupling of sp2-aryl halides, and the cross-couplings with unactivated alkyl halides are far less reported. Herein, we demonstrate that a high-efficiency copper system enabled the coupling of arylborons with various unactivated secondary and primary alkyl halides including bromides, iodides, and even robust chlorides. The present system features broad scope, excellent functionality tolerance, scalability, and practicality. Moreover, the current system could be applied for the late-stage functionalization of complex molecules in moderate to high efficiency.