DFT Calculations Rationalize Unconventional Regioselectivity in PdII-Catalyzed Defluorinative Alkylation of gem-Difluorocyclopropanes with Hydrazones

Density functional theory (DFT) calculations have been conducted to gain insight into the unique formation of the branched alkylation product in the PdII-catalyzed defluorinative alkylation of gem-difluorocyclopropanes with hydrazones. The reaction is established to occur in sequence through oxidative addition, β-F elimination, η1-η3 isomerization, transmetalation, η3-η1 isomerization, 3,3′-reductive elimination, deprotonation/N2 extrusion, and proton abstraction. The rate-determining step of the reaction is identified as the β-F elimination, featuring an energy barrier of 28.6 kcal/mol. The 3,3′-reductive elimination transition states are the regioselectivity-determining transition states. The favorable noncovalent π–π interaction between the naphthyl group of gem-difluorocyclopropane and the phenyl group of hydrazone is found to be mainly responsible for the observed regioselectivity.