Catalyst-Controlled Nitrene Transfer by Tuning Metal:Ligand Ratios: Insight into the Mechanisms of Chemoselectivity

Abstract

Catalyst-controlled, selective nitrene transfer is often challenging when both C−H and CC bonds are present in a substrate. Interestingly, a simple change in the Ag(I):L ratio (L = bidentate N,N-donor ligand) enables tunable, chemoselective nitrene transfer that favors either C C bond aziridination using an ∼1:1 Ag:L ratio (AgLOTf) or insertion into a C−H bond when the Ag:L ratio in the catalyst is 1:2 (AgL 2 OTf). In this paper, mechanistic studies, coupled with kinetic profiling of the entire reaction course, are employed to examine the reasons for this unusual behavior. Steady-state kinetics were found to be similar for both AgLOTf and AgL 2 OTf; both complexes yield electronically similar reactive intermediates that engage in nitrene transfer involving formation of a short-lived radical intermediate and barrierless radical recombination. Taken together, experimental and computational studies point to two effects that control tunable chemoselectivity: suppression of aziridination as the steric congestion around the silver center is increased in AgL 2 OTf and a decrease in the rate of C−H insertion with AgLOTf in comparison to AgL 2 OTf. The observation that the sterics of Ag catalysts can be varied, with minor effects on the electronic features of the putative nitrene, has important implications for the development of other silver catalysts that enable tunable, site-selective C−H bond aminations.

Inverting Steric Effects: Using “Attractive” Noncovalent Interactions To Direct Silver-Catalyzed Nitrene Transfer

“…22 As with all metal-catalyzed NT reactions reported to date, the negative ρ value indicates a buildup of positive charge in the transition state (TS). 13,17a,20 These results imply an earlier TS for reactions catalyzed by Ag(tpa)OTf, as compared to other catalysts proceeding via stepwise NT; however, the exact reasons for these mechanistic differences are currently unclear. 17e …”

“…Interestingly, examination of KIE and Hammett ρ values showed similarities between Ag(tpa)OTf and Rh 2 L n (Scheme 1B), 13,17a yet the selectivity of the former was more reminiscent of the results noted with Ru, Fe, and Co complexes. 8c,20,23 While this might be attributed to stepwise NT promoted by Fe, Ru, Co, and Ag, we considered the possibility that additional factors might be responsible for the behavior observed with Ag(tpa)OTf.…”

“…17a Further optimization yielded several observations relevant to a deeper understanding of the mechanism of intramolecular NT promoted by Ag(tpa)OTf, including the possibility that π ··· π or Ag··· π interactions play important roles in directing selectivity.…”

“…This mechanism occurs with a single HT transition state, followed by a radical recombination step displaying no energy barrier; radical species are not stationary points on the potential energy surface. 17e …”

“…Of the transition metals that catalyze NT, 4−11 we selected Ag(I) complexes to study directed amination due to their diverse coordination environments, 16,17 Lewis acidity, and ability to engage in cation− π interactions. Substrates adorned with traditional directing groups, such as pyridines and imines, proved unsuccessful, as strong interactions between Ag and directing groups precluded our ability to tune the site of the C−H amination.…”