Direct Vinylation and Difluorovinylation of Arylboronic Acids Using Vinyl- and 2,2-Difluorovinyl Tosylates via the Suzuki−Miyaura Cross Coupling

Abstract

General reaction conditions were developed for the Pd(0)-catalyzed Suzuki-Miyaura coupling reaction of aryl boronic acids with a simple electrophilic vinylation reagent, vinyl tosylate, providing access to styrene derivatives in good yields. The easily accessible vinyl tosylate represents a stable and less toxic alternative to the vinyl halides and the triflate/nonaflate derivatives. Furthermore, this methodology was expanded to provide a facile and straightforward approach for the introduction of a gem-difluorovinyl substituent onto an aromatic ring using the similar and also readily available 2,2-difluorovinyl tosylate as the electrophilic complement.

Usage of the Carboxylate Leaving Group in Transition-metal-catalyzed Cross-coupling and Related Reactions

“…Vinyl tosylate is also known to couple with organomatals in the presence of a transition metal complex, though the tosylate electrophile is inferior to the halides in terms of availability. 47 To solve the above drawbacks, vinyl acetate has emerged as an ideal electrophilic substrate for the vinylation because it is easy to handle owing to its moderate boiling point. Furthermore, it is comparable in cost to vinyl chloride.…”

Synthesis of Small 3-Fluoro- and 3,3-Difluoropyrrolidines Using Azomethine Ylide Chemistry

“…If this is true, we reasoned that we could trap the intermediate 3-fluoromaleimide with azomethine ylide if we can concomitantly promote the elimination and generation of the azomethine ylide using lithium fluoride. Treatment of a mixture containing 3,3-difluoroimide (14) and azomethine ylide precursor (1) in acetonitrile with lithium fluoride reveals the desired 3α-fluoro-tetraydropyrrolo imide system (16) in good yield. The benzyl group on the pyrrolidine can be selectively exchanged for a Boc group via hydrogenolysis conditions.…”

Facile Synthesis of β,β-Difluorostyrenes via the Negishi Coupling of Thermally Stable 2,2-Difluorovinyl Zinc–TMEDA Complex

“…2 To date several methodologies have been established for the synthesis of ¢,¢-difluorostyrenes. Typically phosphane ylide-based reactions 3 and metal-mediated coupling reactions 4,5 have been used. 6 While the synthetic methods via phosphane ylide intermediates require arylaldehydes and an excess amount of expensive phosphanes, metal-mediated reactions are more straightforward.…”

“…Two types of metal-mediated coupling reactions have been developed: coupling reactions between 2,2-difluorovinylmetal reagents and aryl halides (eq 1) 4 and between arylmetal reagents and difluorovinyl halides. 5 In both cases, the use of difluorovinyl halides, which are rarely commercially available, is required. In 1985, Sauvêtre and Normant achieved the preparation of a difluorovinylzinc reagent directly from commercially available 1,1-difluoroethylene, the smallest compound in the 1,1-difluoro-1-alkene family, by sequential lithiation and zincation.…”