Regiocontrol in Catalytic Reductive Couplings through Alterations of Silane Rate Dependence

[Image: see text] Combinations of ligand, reducing agent, and reaction conditions have been identified that allow alteration in the rate- and regioselectivity-determining step of nickel-catalyzed aldehyde–alkyne reductive couplings. Whereas previously developed protocols involve metallacycle-forming oxidative cyclization as the rate-determining step, this study illustrates that the combination of large ligands, large silanes, and elevated reaction temperature alters the rate- and regiochemistry-determining step for one of the two possible product regioisomers. These modifications render metallacycle formation reversible for the minor isomer pathway, and σ-bond metathesis of the metallacycle Ni–O bond with the silane reductant becomes rate limiting. The ability to tune regiocontrol via this alteration in reversibility of a key step allows highly regioselective outcomes that were not possible using previously developed methods.