CuH-Catalysed Hydroamination of Styrene with Hydroxylamine Esters: A Coupled Cluster Scrutiny of Mechanistic Pathways

A detailed computational exploration of mechanistic intricacies of the copper(I) hydride (CuH)-catalysed hydroamination of styrene with a prototype hydroxylamine ester by a recently reported [(dppbz)CuH] catalyst (dppbz equivalent to {P<<^>>P} equivalent to 1,2-bis(diphenylphosphino)-benzene) is presented. A variety of plausible mechanistic avenues have been pursued by means of a sophisticated computational methodology, from which a general understanding of the factors controlling hydroamination catalysis emerged. The catalytically competent {P<<^>>P}Cu-I hydride, which is predominantly present as its dimer, involves in irreversible hydrocupration proceeding with complete 2,1 regioselectivity to form a secondary {P<<^>>P}Cu-I benzyl intermediate. Its interception with benzylamine ester produces the branched tertiary amine product and {P<<^>>P}Cu-I benzoate upon intramolecular S(N)2 disruption of the amine electrophile's N-O linkage, to precede a highly rapid, strongly exergonic C-N bond-forming reductive elimination. The {P<<^>>P}Cu-I benzoate corresponds to the catalyst resting state and its conversion back into the {P<<^>>P}Cu-I hydride upon transmetalation with a hydrosilane is turnover limiting. The effect of electronic perturbations at the amine electrophile upon the reaction rate for productive hydroamination catalysis and also non-productive reduction of the hydroxylamine ester has been gauged, which unveiled a more fundamental insight into catalytic structure-performance relationships.