Synthesis and Reactions of 3,3-Difluoro-2-exo-methylidene Indolines

Abstract

A dearomative electrophilic fluorination of 2-methylindoles is reported, delivering 3,3-difluoroindolines bearing an exomethylidene. The model substrate was synthesized on up to a 20 mmol scale and was purified by a practical recrystallization as a crystalline bench-stable, yet reactive solid. The olefin is amphoteric and can react both as a nucleophile and as an electrophile. A wide range of metal-free, palladium, rhodium, and copper reactions was explored, forming new C–H, C–B, C–C (alkyl and aryl), C–N, C–O, C–P, and C–S bonds.

Palladium-catalyzed alkynylation of allylic gem-difluorides

“…4 f Simultaneously, Fujii 5 and collaborators have developed a selective method for producing ( Z )-fluoroalkenes through Pd-catalyzed activation of C–F bonds in allylic gem -difluorides, using hydride as the nucleophile (C(sp 3 )–H). Recently, Lautens and co-workers 6 introduced a novel method involving Pd-catalyzed allylic C–F bond activation of 3,3-difluoroindolines with an exomethylidene moiety. This approach enabled sulfonylation (C(sp 3 )–S) and phosphorylation (C(sp 3 )–P) reactions using sodium phenylsulfinate and dialkylphosphite as the respective nucleophiles (Scheme 1A).…”

Palladium-Catalyzed Diversified Synthesis of Monofluorinated Alkenes from Allylic gem-Difluorides through Pd–OH Intermediate

“…In this field, Fujii et al detailed a selective synthesis of ( Z )-fluoroalkenes through Pd-catalyzed allylic activation of C–F bonds in allylic gem -difluorides, employing hydride as the nucleophile. The Paquin group recently reported palladium-catalyzed allylic amination of 3,3-difluoropropenes, yielding 3-fluoroallylic amines and enabling C–C bond formation using malonate as the nucleophile. , Lautens developed Pd-catalyzed allylic C–F bond activation of 3,3-difluoroindolines, achieving sulfonylation and phosphorylation reactions with sodium phenylsulfinate and dialkylphosphite as nucleophiles, respectively (Scheme A).…”