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.

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.

Despite recent progress regarding the metal-catalyzed C–N cross-coupling of (hetero)aryl (pseudo)halides with NH substrates, such transformations involving sulfinamide nucleophiles are underdeveloped. Herein we report on Ni-catalyzed C–N cross-couplings of this type, employing primarily tert-butanesulfinamide (i.e., Ellman’s sulfinamide) as a test nucleophile. Inexpensive and abundant (hetero)aryl chlorides proved to be suitable reaction partners in such reactions when using (L)Ni(o-tol)Cl (L = CyPAd-DalPhos or PhPAd-DalPhos) precatalysts. We also present results of an experimental and computational study focusing on C–N reductive elimination involving newly prepared and isolated sulfinamido (L)Ni(o-tol)(NHS(O)tBu) complexes, in which deprotonation leading to the formation of the putative anionic nitrene species [(L)Ni(o-tol)(NS(O)tBu)]− represents the preferred pathway for C–N reductive elimination, in keeping with our past study of related sulfonamido complexes.

The development of Ni-catalyzed C À N crosscouplings 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)NEt 2 ) demonstrated herein is unprecedented for any reported catalyst system for sulfonamide CÀN cross-coupling (Pd, Cu, Ni, or other). Preliminary competition experiments and relevant coordination chemistry studies are also presented.Supporting information and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.org/10.1002/anie.202002392. Figure 1. N-Arylation of sulfonamides with (hetero)aryl (pseudo)halides. A) The structure of celecoxib. B) Metal-catalyzed CÀN crosscouplings of sulfonamides. C) DalPhos ligands used in Ni-catalyzed cross-couplings. Angewandte Chemie Communications