Stereoselective Palladium‐Catalyzed C−F Bond Alkynylation of Tetrasubstituted gem‐Difluoroalkenes

Abstract

A stereoselective Pd(PPh3)4‐catalyzed C−F bond alkynylation of tetrasubstituted gem‐difluoroalkenes with terminal alkynes has been developed. This method gives access to a great variety of conjugated monofluoroenynes bearing a tetrasubstituted alkene moiety with well‐defined stereochemistry. Chelation‐assisted oxidative addition of Pd to the C−F bond is proposed to account for the high level of stereocontrol. An X‐ray crystal structure of a key monofluorovinyl PdII intermediate has been obtained for the first time as evidence for the proposed mechanism.

Nickel‐Catalyzed Stereo‐ and Enantioselective Cross‐Coupling of gem‐Difluoroalkenes with Carbon Electrophiles by C−F Bond Activation

“…The current efficient protocols involve installation of fluorinated groups [4] or, alternatively, selective activation and functionalization of a C−F bond in a multi‐fluorinated compound [5] . The latter strategy has recently proven to be more efficient and prevalent, and defluorinative arylation, [6] alkylation, [7] borylation, [8] silylation, [9] carbonylation, [10] hydrogenation [11] and alkynylation [12] of gem ‐difluoroalkenes have been developed successively to build a range of substituted monofluoroalkenes. Despite these successes, the highly desirable asymmetric variant involving catalytic C−F bond activation of gem ‐difluoroalkenes with readily available reagents to construct enantioenriched monofluoroalkenes remains elusive.…”

“…The key steps in the racemic transformation involve an alkyl radical addition to gem ‐difluoroalkenes to form C−C bond, and β‐F elimination to cleave C−F bond. In our strategy, the use of gem ‐difluoroalkenes bearing esters as directing groups can assist the stereoselective C−F bond activation via oxidative addition, [12] and recombination of the formed nickel complex with a long‐lived benzylic radical can control enantioselectivity.…”

“…The reaction was initiated with the in situ formation of nickel complex A through Br−I exchange between Ni‐L6 and NaI; A undergoes reduction with B 2 pin 2 and a base to generate Ni 0 species B through transmetallation and reductive elimination of I‐BPin [25] . With chelation assistance from the ester group, complex B undergoes stereodifferentiating C−F bond activation to form complex D via intermediate C [12] . The resulting Ni II species D then combines with cage‐escaped sec ‐benzyl radical 2′ to afford Ni III complex E , [26] which upon reductive elimination generates chiral product 3 and Ni I complex F [27] .…”