Access to Divergent Fluorinated Enynes and Arenes via Palladium-Catalyzed Ring-Opening Alkynylation of gem-Difluorinated Cyclopropanes

Abstract

Herein, we describe a palladium-catalyzed alkynylation of gem-difluorinated cyclopropanes via C–C bond activation/C–F bond cleavage, followed by C–C­(sp) coupling. The new approach proceeds with broad substrate scope under mild reaction conditions, whereas both 1,1-disubstituted and complex-molecule-modified gem-difluorinated cyclopropanes react smoothly with high stereoselectivity. The developed method provides efficient and convenient ways access to diversity of important fluorinated enynes and arenes by slightly modification of the reaction conditions.

Rhodium-Catalyzed Direct Allylation of Simple Arenes by Using Gem-Difluorinated Cyclopropanes as Allyl Surrogates

“…After this, a series of palladium-catalyzed ring-opening reactions of gem-difluorinated cyclopropanes were developed rapidly. The cross-coupling reactions of gem-difluorinated cyclopropanes with nucleophiles such as organoboronic acids 7 , terminal alkynes 8 , or borylalkenyl nucleophiles generated in situ from internal alkynes and B 2 pin 2 in the presence of copper complex as a co-catalyst, 9 were successively developed by the same group in 2019, 2020, and 2021, respectively (Schemes 2a-c). At the same time, Zhang and co-workers developed a palladium-catalyzed crosscoupling of gem-difluorinated cyclopropanes with arylsulfinates to synthesize 2-fluoroallylic sulfones (Scheme 2d), 10 and the Lin group reported an allylation/dearomatization reaction of -naphthols/indoles by using gem-difluorinated cyclopropanes as allyl sources under palladium catalysis (Scheme 2e).…”

Cu/Pd-Catalyzed cis-Borylfluoroallylation of Alkynes for the Synthesis of Boryl-Substituted Monofluoroalkenes

“…Numerous studies have been conducted with the purpose of constructing valuable monofluoroalkene compounds. Methods for this process include Julia-Kocienski olefination, the Horner–Wadsworth–Emmons reaction, and the catalytic conversion of fluorinated building blocks. , More recently, the Pd-catalyzed C–C activation/C–F bond cleavage of readily available gem- difluorinated cyclopropane has been demonstrated as an efficient strategy for accessing monofluoroalkenes. , In view of the extremely efficient borylative difunctionalization of alkynes − and the importance of monofluoroalkene, we envision that a three-component reaction involving gem- difluorocyclopropane, alkynes, and bis­(pinacolato)­diboron (B 2 pin 2 ) may simplify the synthesis of new-generation boryl-monofluoroalkene compounds. The insertion of Cu–B into triple bonds can be easily realized by the use of Cu catalysts.…”

The preparation and properties of 1,1-difluorocyclopropane derivatives

“…fluorinated cyclopropanes 161 with boronic acids which afforded the monofluoroalkenes 163 [120]. Very recently, the groups by Gong and Fu [121] studied the Pd-catalyzed alkynylation of cyclopropanes 161 with terminal alkynes that led to the formation of the isomeric fluorinated enynes 164 and 165. As highlighted by these pioneering works [119][120][121][122], the direct Pd-catalyzed transformation of gem-difluorocyclopropanes to monofluoroalkenes is a promising approach towards the synthesis of fluorinated alkenes.…”