Copper-catalysed electrophilic carboamination of terminal alkynes with benzyne looked at through the computational lens.

A detailed computational mechanistic study of the copper-catalysed three-component-type electrophilic carboamination of terminal alkynes with benzyne and an archetypal O -benzoylhydroxylamine electrophile is presented. Probing various plausible pathways for relevant elementary steps and scrutinising performance degradation pathways, with the aid of a reliable computational protocol applied to a realistic catalyst model combined with kinetic analysis, identified the pathways preferably traversed in productive catalysis. It entails rapid alkynylcupration of in situ generated benzyne to deliver the arylcopper nucleophile that undergoes amination with the O -benzoylhydroxylamine electrophile to afford copper benzoate. Umpolung-enabled electrophilic amination favours a multistep SN 2-type oxidative addition/N-C bond-forming reductive elimination sequence involving a short-lived formal {P^P}CuIII carboxylate amido aryl intermediate. SN 2-type displacement of the benzoate leaving group at the arylcopper nucleophile, which represents the catalyst resting state, is predicted to be the turnover limiting step. Alkynolysis transforms copper benzoate back to catalytically competent alkynylcopper. The computational probe of a wider range of substrates reveals that only severely ring-strained C6 -arynes, C6 -cycloalkynes and electron-deficient cyclopropenes featuring a highly reactive C≡C linkage could replace benzyne. Moreover, strict control of stationary benzyne concentration is indispensable for electrophilic carboamination to ever become achievable.