A Versatile Tripodal Cu(I) Reagent for C–N Bond Construction via Nitrene-Transfer Chemistry: Catalytic Perspectives and Mechanistic Insights on C–H Aminations/Amidinations and Olefin Aziridinations

Abstract

A Cu(I) catalyst (1), supported by a framework of strongly basic guanidinato moieties, mediates nitrene-transfer from PhI═NR sources to a wide variety of aliphatic hydrocarbons (C-H amination or amidination in the presence of nitriles) and olefins (aziridination). Product profiles are consistent with a stepwise rather than concerted C-N bond formation. Mechanistic investigations with the aid of Hammett plots, kinetic isotope effects, labeled stereochemical probes, and radical traps and clocks allow us to conclude that carboradical intermediates play a major role and are generated by hydrogen-atom abstraction from substrate C-H bonds or initial nitrene-addition to one of the olefinic carbons. Subsequent processes include solvent-caged radical recombination to afford the major amination and aziridination products but also one-electron oxidation of diffusively free carboradicals to generate amidination products due to carbocation participation. Analyses of metal- and ligand-centered events by variable temperature electrospray mass spectrometry, cyclic voltammetry, and electron paramagnetic resonance spectroscopy, coupled with computational studies, indicate that an active, but still elusive, copper-nitrene (S = 1) intermediate initially abstracts a hydrogen atom from, or adds nitrene to, C-H and C═C bonds, respectively, followed by a spin flip and radical rebound to afford intra- and intermolecular C-N containing products.

Nitrene Insertion into Aromatic and Benzylic C−H Bonds Catalyzed by Copper Complexes of Fluorinated Bis‐ and Tris(pyrazolyl)borates

“…The optimized transition state suggests a step-wise nitrene addition followed by proton transfer rather than a concerted nitrene insertion, as was proposed by Hou et al [49] This result agrees with previous experiment-theory research on nitrene two-step aziridination using substituted styrenes as substrate studies. [52,53] The nitrene addition pathway has a lower barrier than arene sp 2 HAA (17.0 vs. 27.0 kcal mol À 1 ), suggesting it is the preferred route for functionalization of the mesitylene sp 2 CÀ H bonds. NBO analysis shows that nitrene addition leads to an amido-copper intermediate as illustrated in Figure 3, with a Cu(I)-N À (Ns)(Mes + ) configuration.…”

“…[51] Significant spin density is found on both the nitrene nitrogen and the copper, Information). [52,53] The nitrene addition pathway has a lower barrier than arene sp 2 HAA (17.0 vs. 27.0 kcal mol À 1 ), suggesting it is the preferred route for functionalization of the mesitylene sp 2 CÀ H bonds. Additionally, for mesitylene, one expects an additional steric advantage for activation at a benzylic versus an arene CÀ H bond.…”

Guanidine Metal Complexes for Bioinorganic Chemistry and Polymerisation Catalysis

“…They gave hints that the mechanism differentiates from that of the rhodium-mediated nitrene transfer. Hammett correlations support a mechanism where carboradicals generated by H atom abstraction play a crucial role [132]. …”

Metal-Catalyzed and Metal-Free Intermolecular Amination of Light Alkanes and Benzenes

“…In a single example, Stavropoulos and co-workers 51 show (Scheme 10) that the light alkane 2-methylbutane (limiting reagent) can be aminated by PhINTs (2.0 equiv.) in the presence of [Cu I (TMG 3 trphen)][PF 6 ] (10 mol%) and 5 Å molecular sieves in MeCN/chlorobenzene (1:10 v/v) at room temperature.…”