Computational mechanistic elucidation of the rare earth metal-mediated cycloamidination of aminoalkenes with nitriles.

A detailed computational probe of the rare earth metal-mediated intramolecular amidination of aminoalkenes with nitriles by an archetypical [Y{N(SiMe3)2}3] precatalyst is presented. The mechanistic picture derived from smooth energy profiles, acquired by employing a reliable computational protocol applied to a realistic catalyst model, conforms to available experimental data that includes a significant primary KIE. Sequential Y-N silylamide aminolysis transforms the precatalyst into a multitude of silylamide/amide compounds, of which the bis-amine coordinated [Y{N(SiMe3)2}(NRR')2] is the most abundant, capable of promoting cycloamidination. Nitrile insertion is irreversible and readily furnishes the κ2-N-amidinate yttrium intermediate, which readily rearranges into more stable isomers featuring κ2-N,Δ and κ1-N(imine) amidinate ligations. Its bis-amine adduct likely represents the catalyst resting state. The alkenylamidine becomes accessible through kinetically affordable Y-N amidinate bond protonolysis, which can best be viewed as a kinetically mobile equilibrium that favours the amidinate. The generation of 2-imidazoline product via N-C bond forming amidinate cyclisation favours a stepwise σ-insertive cyclisation/Y-C alkyl aminolysis sequence over an otherwise kinetically prohibitive proton-triggered concerted N-C/C-H bond forming process. The operative σ-insertive pathway entails reversible olefin 1,2-insertion followed by turnover-limiting Y-C alkyl aminolysis at the short-lived 4-imidazolylalkyl intermediate. The DFT estimated primary KIE associated with aminolysis is gratifyingly close to the observed value, thereby supporting the derived mechanistic view.