Pd/NHC-Controlled Regiodivergent Defluorinative Allylation of gem-Difluorocyclopropanes with Allylboronates

Controlling the selectivity of synthetically useful reactions has been a longstanding objective of organic chemistry. We report a regiodivergent synthetic protocol allowing access to diverse fluorinated 1,5-dienes through Pd/NHC-catalyzed ring-opening allylation of gem-difluorocyclopropanes. Density functional theory (DFT) calculations on regioselectivity-determining transition states provided critical insight into the design of the NHC ligand for switching regioselectivity. Consistent with the DFT predictions, N-heterocyclic carbene (NHC) ligands with bulky ortho substituents favored branched allylation, with the IHept ligand providing > 20:1 branched/linear regioselectivity. NHC ligands with less hindered ortho substituents such as IMes favored the thermodynamically more stable linear products. We were able to carry out late-stage modification of various complex molecules using this protocol. Our ligand-controlled approach provides efficient access to regioisomeric fluorinated 1,5-dienes from the same starting materials and constitutes a valuable addition to the toolbox of diversity-oriented synthesis.