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.

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

“…We were able to isolate and characterize a novel monofluorovinylpalladium-(II) iodide intermediate (Int-1) as a single diastereomer. Its structure was unambiguously confirmed by X-ray crystallography, [25] showing that the Pd adopts a square-planar geometry with the two PPh 3 ligands arranged in a trans manner. To the best of our knowledge, this is the first report of a Pd complex derived from gem-difluoroalkenes.…”

“…The structure and E-alkene configuration of the monofluoroenynes 3 were unambiguously confirmed by X-ray crystallography of the biphenyl product 3 ah. [25] Remote substituents such as nitrile (3 ai) and methyl ester (3 aj) groups on the biphenyl framework were compatible. Benzylsubstituted difluoroalkenes were not as reactive as their (hetero)aryl counterparts under standard conditions.…”

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

“…[24] The reaction was initiated with the in situ formation of nickel complex A through BrÀ 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 CÀ 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] This species abstracts a halide from electrophile 2 to form the stabilized benzylic radical 2'. [28] Finally, Ni I -halide species F undergoes SET to regenerate Ni II complex A and close the catalytic cycle.…”

Pd/Cu‐Catalyzed Defluorinative Carbonylative Coupling of Aryl Iodides and gem‐Difluoroalkenes: Efficient Synthesis of α‐Fluorochalcones

“…(a)]. One of the key steps in these transformations is the activation of the C−F bond by β‐F elimination or oxidative insertion under the assistant of directing group [7o,p,q] . To the best of our knowledge, despite these successful examples, carbonylation of C−F bond has not been realized yet.…”