Synthesis of gem-Difluoroalkenes via Nickel-Catalyzed Allylic Defluorinative Reductive Cross-Coupling

Abstract

In this protocol, we report an allylic defluorinative reductive cross-coupling reaction for C–C bond formation. Under the Ni-catalysis the challenging C­(sp3)–F bond cleavage of trifluoromethyl-substituted alkenes was achieved with easily accessible primary, secondary and tertiary alkyl halides as the coupling partners and Zn-powder as reducing agent. This process provides an efficient and convenient entry to gem-difluoroalkenes bearing various sensitive functional groups under mild reaction conditions. Moreover, this method proves to be suitable for late-stage functionalization of multifunctional complex molecules.

Nickel-catalyzed allylic defluorinative alkylation of trifluoromethyl alkenes with reductive decarboxylation of redox-active esters

“…It is worth mentioning that a number of products ( e.g. , 3ae , 3al , 3ao , 3ap , 3aq and 3ar ) were difficult and even chemically infeasible to prepare through the use of a cross-coupling with the corresponding alkyl halides 16. A one-pot synthesis at the gram scale further demonstrated the simplicity and usability of this new method.…”

Manganese-mediated reductive functionalization of activated aliphatic acids and primary amines

“…Previously, the defluorinative S N 2′ reaction of 1-(trifluoromethyl)alkenes with different nucleophiles with or without a catalyst offers a straightforward access to substituted gem-difluoroalkenes 71 . The electrophilic alkyl halides or aliphatic RAE, were also successfully coupled with 1-(trifluoromethyl) alkenes in the presence of a nickel catalyst and stoichiometric amount of zinc reductant 72,73 .…”

Migratory functionalization of unactivated alkyl bromides for construction of all-carbon quaternary centers via transposed tert-C-radicals

“…To explain the results in Fig. 2, we propose a tertiary carbon radical is generated and participates in the crucial C-C bond formation step [72][73][74][75] . The oxidative addition of alkyl bromides to low-valent Ni catalysts usually takes place through a cascade of single electron transfer and alkyl radical generating steps 76 .…”