Nickel-Catalyzed O‑Arylation of Primary or Secondary Aliphatic Alcohols with (Hetero)aryl Chlorides: A Comparison of Ni(I) and Ni(II) Precatalysts

A comparative experimental and computational study examining the interplay of the ancillary ligand structure and Ni oxidation state in the Ni-catalyzed C­(sp2)–O cross-coupling of (hetero)­aryl chlorides and primary or secondary aliphatic alcohols is presented, focusing on PAd-DalPhos (L1)-, CyPAd-DalPhos (L2)-, PAd2-DalPhos (L3)-, and DPPF (L4)-ligated [(L)­NiCl] n (n = 1 or 2) and (L)­Ni­(o-tol)Cl precatalysts. Both L1 and L2 were found to outperform the other ligands examined, with the latter proving to be superior overall. While Ni­(II) precatalysts generally outperformed Ni­(I) species, in some instances the catalytic abilities of Ni­(I) precatalysts were competitive with those of Ni­(II). Density-functional theory calculations indicate the favorability of a Ni(0)/Ni­(II) catalytic cycle featuring turnover-limiting C–O bond reductive elimination over a Ni­(I)/Ni­(III) cycle involving turnover-limiting C–Cl oxidative addition.