Identification of a Nitrenoid Reductive Elimination Pathway in Nickel-Catalyzed C–N Cross-Coupling

Abstract

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.

A Borane Lewis Acid in the Secondary Coordination Sphere of a Ni(II) Imido Imparts Distinct C–H Activation Selectivity

“…To overcome this challenge, we hypothesized that a strong Lewis base might competitively bind the BBN Lewis acid, thus rendering the Ad-NH unit available for C−N reductive elimination. When 6a was treated with a combination of 9-azajulolidine and sodium t-pentoxide, 101 we observed the reductive elimination product N-phenyl-N-adamantyl amine in 26% yield (Figure 11). 102,103 These results represent a proof of principle that reductive elimination can be induced using a suitable set of reagents.…”

Structure–Reactivity Relationships of Buchwald-Type Phosphines in Nickel-Catalyzed Cross-Couplings

“…Access to 7 gave us a unique opportunity to stoichiometrically observe and study N−H deprotonation and subsequent C−N reductive elimination from an on-cycle amine-bound Ni complex. 83,84 We found that combining 7 with a slight excess of NaOt-Bu in a stoichiometric NMR study under inert atmosphere gave C−N coupled product in 89% NMR yield (Figure 8A), which had reached maximum conversion by the time the spectrum was taken (<5 min). This indicates that the deprotonation and reductive elimination steps occurred rapidly, even at room temperature, suggesting that the C−N bond-forming transition state barrier from the deprotonated complex is low.…”

Structure-Reactivity Relationships of Buchwald-Type Phosphines in Nickel-Catalyzed Cross-Couplings

“…Access to 6 gave us a unique opportunity to stoichiometrically observe and study N-H deprotonation and subsequent C-N reductive elimination from a catalytically oncycle amine-bound Ni complex. 76,77 We found that combining 6 with a slight excess of NaOt-Bu in a stoichiometric NMR study under inert atmosphere gave C-N coupled product in 89% NMR yield (Scheme 4A), which had reached maximum conversion by the time the spectrum was taken (< 5 minutes). This indicates that the deprotonation and reductive elimination steps occurred rapidly, even at room temperature, suggesting that C-N bond-forming transition state barrier from the deprotonated complex is low.…”