DFT Calculations Rationalize Unconventional Regioselectivity in Pd II -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 Pd II -catalyzed defluorinative alkylation of gem -difluorocyclopropanes with hydrazones. The reaction is established to occur in sequence through oxidative addition, β-F elimination, η 1 -η 3 isomerization, transmetalation, η 3 -η 1 isomerization, 3,3'-reductive elimination, deprotonation/N 2 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.