The development of Ni‐catalyzed C−N cross‐couplings of sulfonamides with (hetero)aryl chlorides is reported. These transformations, which were previously achievable only with Pd catalysis, are enabled by use of air‐stable (L)NiCl(o‐tol) pre‐catalysts (L=PhPAd‐DalPhos and PAd2‐DalPhos), without photocatalysis. The collective scope of (pseudo)halide electrophiles (X=Cl, Br, I, OTs, and OC(O)NEt2) demonstrated herein is unprecedented for any reported catalyst system for sulfonamide C−N cross‐coupling (Pd, Cu, Ni, or other). Preliminary competition experiments and relevant coordination chemistry studies are also presented.

The Ni­(II) precatalyst (C1) featuring the phosphonite ancillary ligand Phen-DalPhos (L1) was employed in the cross-coupling of (hetero)­anilines with (hetero)­aryl chlorides and in the diarylation of ammonia with (hetero)­aryl chlorides to afford heteroatom-dense di­(hetero)­arylamines. The PAd2-DalPhos precatalyst C4 provided complementary reactivity in cross-couplings of indoles with (hetero)­aryl chlorides. Taken together, the demonstration of room-temperature reactivity within each of the reaction classes examined and the observation of useful chemoselectivity at low loading (≤0.5 mol % Ni) and on gram-scale distinguishes C1 and C4 from other metal catalysts (i.e., copper, palladium, nickel, or other) within the field of C–N cross-coupling chemistry.

While the Ni-catalyzed cross-coupling of primary or secondary aliphatic alcohols and (hetero)aryl electrophiles is known, related crosscouplings involving tertiary aliphatic alcohols, with a broad scope, are challenging. Herein we disclose that a Ni II precatalyst featuring the ligand CgPhen-DalPhos is unusual in its ability to promote the C−O cross-coupling of tertiary aliphatic alcohols with (hetero)aryl halides (Cl, Br, and I) or phenol derivatives (OMs and OPiv). An exploration of substrate scope and competition experiments help to shed light on the capabilities and reactivity preferences of this catalyst system.

Whereas the (bisphosphine)Ni-catalyzed C−N cross-coupling of (hetero)aryl (pseudo)halides with NH nucleophiles represents a useful method for the synthesis of (hetero)anilines, our mechanistic understanding of such cross-couplings is incomplete, especially regarding key C−N reductive elimination steps that are often invoked as turnoverlimiting. In this combined experimental and computational study, we provide evidence of a bifurcated C−N reductive elimination pathway for cross-couplings of tBuNH 2 and (aryl′)SO 2 NH 2 employing (L1)Ni(aryl)Cl as the precatalyst (L1 = PhPAd-DalPhos). In contrast with direct C−N reductive elimination that proceeds from the nickel alkylamido complex (L1)Ni(aryl)(NHtBu), we provide evidence of a previously undocumented base-promoted pathway involving deprotonation of the nickel sulfonamido complex (L1)Ni(aryl)(NHSO 2 (aryl′)) to give the anionic nickel nitrenoid species [(L1)Ni(aryl)(NSO 2 (aryl′))] − , from which C−N reductive elimination occurs preferentially.

The CÀ N cross-coupling of (hetero)aryl (pseudo)halides with NH substrates employing nickel catalysts and organic amine bases represents an emergent strategy for the sustainable synthesis of (hetero)anilines. However, unlike protocols that rely on photoredox/electrochemical/reductant methods within Ni I/III cycles, the reaction steps that comprise a putative Ni 0/II CÀ N cross-coupling cycle for a thermally promoted catalyst system using organic amine base have not been elucidated. Here we disclose an efficient new nickelcatalyzed protocol for the CÀ N cross-coupling of amides and 2'-(pseudo)halide-substituted acetophenones, for the first time where the (pseudo)halide is chloride or sulfonate, which makes use of the commercial bisphosphine ligand PAd2-DalPhos (L4) in combination with an organic amine base/halide scavenger, leading to 4quinolones. Room-temperature stoichiometric experiments involving isolated Ni 0, I, and II species support a Ni 0/II pathway, where the combined action of DBU/NaTFA allows for room-temperature amide cross-couplings.