Examining the Impact of Heteroaryl Variants of PAd-DalPhos on Nickel-Catalyzed C(sp2)‑N Cross-Couplings

We report herein on the synthesis of new heteroaryl analogues of PAd-DalPhos and related bis­(di­(o-tolyl)­phosphino) ancillary ligand variants based on pyridine or thiophene backbone structures, and their application in nickel-catalyzed C­(sp2)-N cross-couplings under challenging reaction conditions. The 3,4-disubstituted thiophene-based ancillary ligand ThioPAd-DalPhos (L8) was observed to be particularly effective in the nickel-catalyzed C­(sp2)-N cross-coupling of primary alkylamines, and the derived precatalyst (L8)­NiCl­(o-tolyl) (C2) was found to offer improved performance versus the related PAd-DalPhos-derived precatalyst C1 in such transformations. In using C2, cross-couplings of various primary alkylamines and (hetero)­aryl-X electrophiles (X = Cl, Br, OTs) proceeded under unprecedentedly mild reaction conditions (0.25–0.50 mol % Ni), including examples conducted at room temperature. Also reported herein are the results of our combined experimental/DFT computational study directed toward gaining insight regarding the improved catalytic performance of C2 versus C1.