Nickel-catalyzed construction of C(sp3)-C(sp3) bonds with alkyl halides and diazo compounds for accessing all-carbon quaternary centers

Transition-metal catalyzed formation of C–C bonds has emerged as an effective strategy for constructing all-carbon quaternary centers, which represent a persistent synthetic challenge in organic synthesis. However, most reported methods afforded tertiary C(sp 3 )–C(sp 2 ) or tertiary–primary C(sp 3 )–C(sp 3 ) bonds, while the construction of sterically congested tertiary–secondary or tertiary–tertiary C(sp 3 )–C(sp 3 ) bonds remains exceptionally challenging and rare. To address this issue, a nickel-catalyzed reaction was disclosed to forge tertiary–secondary C(sp 3 )–C(sp 3 ) bonds efficiently with tertiary alkyl halides and diazo compounds through migratory insertion of a nickel carbene followed by a cross-coupling process. Furthermore, the utilization of tertiary alkyl halides in metal carbene-involved cross-coupling reactions is still unaccomplished. This work provides a general strategy to address the above limitation by demonstrating the viability of tertiary, secondary and primary alkyl halides with nickel catalysis. Both experimental investigations and DFT computational studies can support the designed reaction pathway. A method for tertiary–secondary C(sp 3 )–C(sp 3 ) bond formation was disclosed with the generation of all-carbon quaternary centers. This transformation not only complements the scope of organic halides in metal carbene-involved cross-coupling reactions but also employs general tertiary alkyl halides in nickel hydride catalysis successfully.