Enantio‐, Diastereo‐ and Regioselective Synthesis of Chiral Cyclic and Acyclic gem‐Difluoromethylenes by Palladium‐Catalyzed [4+2] Cycloaddition

gem-Difluoromethylene moieties are attractive in medicinal chemistry due to their ability to mimic other more ubiquitous functional groups. Thus, effective asymmetric methods for their construction are highly desirable, especially for the industrial production of chiral drugs. Using a Pd-catalyzed asymmetric [4+2] cycloaddition between substituted-2-alkylidenetrimethylene carbonates and gem-difluoroalkyl ketones, we were able to easily access chiral 1,3-dioxanes that contain a tetrasubstituted difluoroalkyl stereogenic center in cyclic and acyclic skeletons. A novel phosphoramidite ligand, which contains a bulky 1,1-dinaphthylmethanamino moiety, was developed to provide the products in high yield with excellent enantio-, diastereo-, and regioselectivity. Strikingly, the gem-difluoro substitution pattern promotes the reaction, and pentafluoroethylketone, an α,α-difluorinated β-ketoester, and a β-ketosulfone are suitable substrates for this method.