Synthesis of gem-Difluorinated 1,4-Dienes via Nickel-Catalyzed Three-Component Coupling of (Trifluoromethyl)alkenes, Alkynes, and Organoboronic Acids

Abstract

Herein, a nickel-catalyzed defluorinative threecomponent coupling of trifluoromethyl alkenes, internal alkynes, and organoboronic acids is presented. The protocol provides a highly efficient and selective route for the synthesis of structurally diverse gem-difluorinated 1,4-dienes under mild conditions. Mechanistic studies suggest that C−F bond activation proceeds probably through the oxidative cyclization of trifluoromethyl alkenes with Ni(0) species, sequential addition to alkynes, and βfluorine elimination.

Synthesis of Fluorinated Compounds by Nickel-Catalyzed Defluorinative Cross-Coupling Reactions

“…In the presence of a sterically hindered iPr Subsequently, the Ma group developed a similar Ni-catalyzed defluorinative cross-coupling reaction of trifluoromethyl alkenes, arylboronic acids, and internal alkynes (Scheme 63). 93 Various gem-difluorinated 1,4-dienes 183 were obtained in good yields with high regioselectivity. The reaction mechanism is similar to the above results; the alkenyl nickel fluoride intermediate 181 undergoes transmetalation with arylboronic acids, then reductive elimination gives products 183.…”

Chemo-, regio- and stereoselective access to polysubstituted 1,3-dienes via Nickel-catalyzed four-component reactions

“…Among them, organoboron reagents are attractive and valuable synthons owing to their air stability, non-toxicity, abundance, readily accessible, and broad availability in versatile transformations 13 , 18 – 20 . Hence, transition-metal-catalyzed 1,2-difunctionalization of alkynes involving organoboron reagents 13 , 17 , 21 has been proven to be one of the most versatile and powerful tools for the efficient construction of diverse chemical bonds recently. Based on the mechanism, this type of transformation could be divided into radical addition/cross-coupling tactic and carbometallation/cross-coupling platform 3 , 5 , 16 , and both of them are known strategies for the synthesis of value densely substituted alkenes (Fig.…”

Asymmetric dearomative reductive arylallylation of indoles with trifluoromethyl alkenes by nickel catalysis

“…19 However, to achieve this transformation, several challenges have to be overcome, including (1) the establishment of a robust catalyst system that suppresses the unsatisfactory intramolecular reductive Heck reaction of C2-substituted indoles, (2) the avoidance of direct reductive coupling of aryl halides with trifluoromethyl alkenes 20 and (3) simultaneously solving the problems of diastereo- and enantioselectivities for vicinal quaternary and tertiary stereocenters. In line with our continuous interest in reductive coupling chemistry and the synthesis of organofluorine compounds, 21 we herein reported an asymmetric dearomative reductive arylallylation of indoles with trifluoromethyl alkenes by nickel catalysis, which offers an efficient approach towards gem -difluorovinyl-containing indolines bearing vicinal quaternary and tertiary carbon stereocenters with a broad substrate scope, good functional group tolerance, and excellent diastereo- and enantioselectivities (Fig. 1d).…”