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

• DFT calculations show the mechanism details of the palladium-catalyzed defluorinative arylation of gem -difluorocyclopropanes with phenylboronic acids. • The regioselectivity of the reaction originates from electronic effects, while the Z/E -selectivity comes from steric effects. • The chemoselectity is due to the stronger electron-withdrawing capability of the F substituent. 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 C 1 -C 3 bond more than chlorine or hydrogen, making it easier to break. [Display omitted] [ABSTRACT FROM AUTHOR]