Synthesis of Exocyclic Trisubstituted Alkenes via Nickel‐ Catalyzed Kumada‐Type Cross‐Coupling Reaction of gem‐ Difluoroalkenes with Di‐Grignard Reagents

Abstract

Ap ractical, nickel-catalyzed Kumadatype double cross-coupling reactiono fgemdifluoroalkenes with 1,4-or 1,5-di-Grignard reagents wasd eveloped. Ther eactionp roceedede fficiently at room temperature andavariety of cyclization products, arylmethylenecyclopentanes and arylmethylenecyclohexanes, were obtained in high to excellent yields,respectively.

Coupling of Trifluoroacetaldehyde N-Triftosylhydrazone with Organoboronic Acids for the Synthesis of gem-Difluoroalkenes

“…For example, gem -difluoroalkene 2c readily underwent Cu-catalyzed hydrodefluorination to produce Z -fluoroalkene 5 in 72% yield (Scheme a) . Also, 2c smoothly underwent a double cross-coupling with Grignard reagents in the presence of a Ni catalyst (Scheme b) . Upon treatment with thiols, the compound underwent direct nucleophilic substitution to produce α-fluorovinyl thioether 7 in 78% yield with excellent Z selectivity (Scheme c) .…”

Multiple-fold C–F bond functionalization for the synthesis of (hetero)cyclic compounds: fluorine as a detachable chemical handle

“…, methylenecyclopentanes and methylenecyclohexanes) (Scheme 60). 108 Delightedly, a series of aryl, aliphatic, and alkenyl difluoroalkenes had been shown to be amenable to the cyclization with 1.4- or 1,5-di-Grignard reagents under nickel catalysis at room temperature. The reactions were generally finished within 1 h. In addition, no mono-coupled products were formed.…”

“…Soon afterward, the Cao's group intended to accomplish a double Kumada-type cross-coupling reaction of gem-difluoroalkenes with organometallic reagents for the assembly of exocyclic trisubstituted alkenes (e.g., methylenecyclopentanes and methylenecyclohexanes) (Scheme 60). 108 Delightedly, a series Scheme 58 Synthesis of 2-aminobenzofurans.…”

Recent Advances in Transition‐metal‐catalyzed C−C Bond Formation via C(sp2)−F Bond Cleavage

“…In 2016, Cao et al developed the nickel-catalyzed Kumada-Tamao-Corriu coupling of gem-difluoroalkenes with 1,4-or 1,5-di-Grignard reagents (Scheme 28). [37] As a result, various types of exocyclic alkenes were obtained in high to excellent yields under NiCl 2 (dppp) catalysis. Compared to conventional approaches, this method exhibited high selectivity, economy, and very mild reaction conditions, highlighting the specificity of CÀ F activation.…”