Nucleophilicity versus Brønsted basicity controlled chemoselectivity: mechanistic insight into silver- or scandium-catalyzed diazo functionalization

Diazo compounds are popular carbenoid precursors that can react with various transition metals to afford carbene species for further transformations. In this study, density functional theory calculations were used to reveal the mechanisms of silver- and scandium-catalyzed alkylation of diazo compounds to construct compounds with tertiary or quaternary carbon centers. The results show that with a silver(I) salt as the catalyst, the reaction starts with carbenation of silver(I) to afford a Fisher-type silver carbene. Nucleophilic addition of silver carbene complex yields an enolate intermediate, which is followed by annulation/retro-aldol reaction to give a dialkylation product. Meanwhile, scandium(III) salt behaves as Lewis acid to generate free carbene, which is followed by conjugate addition of free carbene to produce an enolate intermediate. Subsequent 1,4-proton transfer to a synthesize monoalkylation product is more favorable than nucleophilic addition process. Computational studies show that formatio...