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

Abstract

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 βketosulfone are suitable substrates for this method.

Palladium-catalyzed decarboxylative [2 + 3] cyclocarbonylation reactions of [60]fullerene: selective synthesis of [60]fullerene-fused 3-vinylcyclopentan-4-ones and cyclopentane-4-carbaldehydes

“…On the basis of the above experimental results and previous literature, 12–15,16 c ,17 the postulated reaction pathways for forming C 60 -fused cyclopentan-4-ones 2 and cyclopentane-4-carbaldehydes 5 are depicted in Scheme 2. In the presence of Pd(PPh 3 ) 4 , π-allyl-Pd intermediate I is initially generated from cyclic carbonate 1 by oxidative addition accompanied by CO 2 extrusion.…”

“…(ii) 2-Alkylidenetrimethylene carbonate as a metal-containing 1,3-all-carbon dipole is disclosed for the first time in the decarboxylation chemistry of cyclic carbonates. 16 c ,17…”

Copper‐Catalyzed Regio‐ and Enantioselective Hydroboration of Difluoroalkyl‐Substituted Internal Alkenes

“…[ 2 ] However, compared with the remarkable progresses in the preparation of fluorinated and trifluoromethylated molecules, [ 3 ] available synthetic approaches to access difluoromethylene‐containing compounds are still relatively limited, especially in a stereoselective manner. [ 4 ] Therefore, the development of new catalytic asymmetric transformations to produce diverse difluoromethylene‐containing chiral molecules is still highly sought‐after.…”