Zirconium-Mediated Hydroaminoalkylation of Conjugated Dienes Probed by a Computational Approach

An in-depth computational probe of the hydroaminoalkylation of 1,3-dienes with N-aryl substituted amines by a tethered bis(ureate)-ligated zirconium compound is reported. The mechanistic proposal derived from smooth energy profiles acquired by employing a reliable computational protocol complies with previous experimental mechanistic studies, providing a more advanced understanding of intricate mechanistic aspects. The high degree of regioselectivity achieved for reversible diene insertion and butenyl tether protonolysis is instrumental for the generation of the main product, (E)-4,1 linear homoallylic amine. Product liberation and regeneration of the zirconaaziridine favours a two-step sequence comprising transamination with incoming amine, followed by β-hydrogen abstraction at the intervening zircona bis-amide. The irreversible transamination is likely the regioselectivity-determining event that dictates the product composition. The β-hydrogen abstraction at the zircona bis-amide, which likely constitutes the catalyst resting state, is turnover limiting. Its DFT-assessed defining barrier conforms with reported catalyst performance data. The role of the smaller, more nucleophilic dimethylamide in the catalytic transformation has been revealed.