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

• Published in: Chemistry : a European journal 2016-06, Vol.22 (24), p.8290-8300
• Main Author: Tobisch, Sven
• Format: Article
• Language: English
• Subjects: ab inito calculations; Amines; Catalysis; Catalysts; Chemistry; Computation; Esters; Hydrides; hydroamination; late transition metals; Pathways; reaction mechanisms; Styrenes; umpolung
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201600230

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≡{P^P}≡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}CuI hydride, which is predominantly present as its dimer, involves in irreversible hydrocupration proceeding with complete 2,1 regioselectivity to form a secondary {P^P}CuI benzyl intermediate. Its interception with benzylamine ester produces the branched tertiary amine product and {P^P}CuI benzoate upon intramolecular SN2 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}CuI benzoate corresponds to the catalyst resting state and its conversion back into the {P^P}CuI 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. Command performance: Computational investigations of diverse pathways of CuH‐mediated hydroamination of styrene with hydroxylamine esters define the most accessible pathways for productive hydroamination catalysis and performance‐limiting reduction of the amine electrophile, from which a general understanding of the factors controlling hydroamination catalysis emerges (see figure).