DFT mechanistic study on the synthesis of 2-fluorinated allylic scaffolds via PdII-catalyzed defluorinative arylation of gem-difluorocyclopropanes with phenylboronic acids

DFT calculations were conducted to understand the mechanism details and the Z/E-, regio-, and chemoselectivities observed in the synthesis of 2-fluorinated allylic scaffolds through PdII-catalyzed defluorinative arylation of gem-difluorocyclopropanes with arylboronic acids. The reaction is determined to proceed sequentially through oxidative addition, β-F elimination, two consecutive transmetalations, and reductive elimination. The β-F elimination dictates the Z/E-selectivity, primarily influenced by steric effects, while the reductive elimination step controls the regioselectivities, driven by electronic effects. The second transmetalation process serves as the bottleneck process with a free energy barrier of 26.5 kcal/mol. The chemoselective preference for gem-difluorocyclopropane over its corresponding chloride and its unsubstituted parent is attributed to the stronger electron-withdrawing capability of the F substituent compared to Cl and H, which polarizes the C1-C3 bond more than chlorine or hydrogen, making it easier to break.