Cobalt‐Catalyzed Allylic Defluorinative Cross‐Electrophile Coupling between 1,1‐Difluoroalkyl Halides and α‐Trifluoromethyl Styrenes

Abstract

In this protocol, we apply reductive cobalt catalysis in the allylic defluorinative cross‐electrophile coupling reaction between 1,1‐difluoroalkyl halides and α‐trifluoromethyl styrenes. This reaction features broad substrate scope (39 examples), good tolerance of various functionalities, and circumvention of pregenerating organometallics, offering a general synthetic route to prepare diverse organofluorines incorporating both a gem‐difluoroalkene and a gem‐difluoroalkane moiety.

Nickel-Catalyzed Cross-Electrophile Ring Opening/gem-Difluoroallylation of Aziridines

“…During the optimization of the reaction conditions, we noticed that the presence of a metal halide is essential for the desired reaction, which supports a reaction pathway involving aziridine iodolysis , followed by XEC of trifluoromethyl-substituted alkenes with the iodolysis product. , To confirm it, we carried out the reaction between alkene 1a and benzyl iodide 5 (Scheme ). Indeed, the allylic defluorinative cross-coupling product 3aa was obtained in a 17% yield with the hydrobenzylation product 3aa′ as the byproduct.…”

“…gem -Difluoroalkenes have attracted increased interest from the organic community in recent years , because such moieties are not only present as characteristic structural units in numerous biologically active compounds but also serve as the precursors to reach other fluorine-containing compounds . Among many strategies, transition-metal-catalyzed allylic defluorinative cross-electrophile coupling (XEC) of trifluoromethyl-substituted alkenes developed by Wang − and others offers a unique reaction pathway to prepare functional-group-rich gem -difluoroalkenes starting from readily available organic electrophiles, including alkyl halides, ,, carbonyl compounds, , acetals, epoxides, oxime esters, , activated carboxylic esters, Katritzky salts, cycloalkyl silyl peroxides, and alkene-tethered aryl halides…”

Visible-light-driven selective difluoroalkylation of α-CF3 alkenes to access CF2-containing gem-difluoroalkenes and trifluoromethylalkanes

“…13 Moreover, a cobalt-catalyzed allylic defluorinative cross-coupling reaction between bromodifluoro substrates and α-trifluoromethyl styrenes using zinc as a stoichiometric reductant was recently reported by Wang (Scheme 1c, left). 14 Nevertheless, the photoredox generation of CF 2 -containing gem -difluoroalkenes and trifluoromethylalkanes from BrCF 2 R-type derivatives (bromodifluoroacetates and bromodifluoroacetamides) under mild conditions has remained elusive.…”

Chromium-catalyzed allylic defluorinative acylation of trifluoromethyl-substituted alkenes with acyl oxime esters

“…2 Consequently, the synthesis of gem -difluoroalkenes has received considerable attention from organic chemists in the last decades, 3 leading to the establishment of two main strategies, which rely on functional group conversion 4 or allylic defluorinative cross-coupling of trifluoromethyl-substituted alkenes. 5 In the recent years, our group 6–12 and others 13 implemented the reductive coupling in the allylic defluorination of trifluoromethyl-substituted alkenes, enabling the efficient synthesis of structurally complex functional-group-rich gem -difluoroalkenes starting from readily available organic electrophiles, which include alkyl halides, 6,13 c , d carbonyl compounds, 7,13 e acetals, 8 epoxides, 9 cyclic oxime esters, 10,13 a activated carboxylic acid esters, 13 b Katritzky salts, 11 cycloalkyl silyl peroxides, 12 and alkene-tethered aryl halides 13 f (Scheme 1A).…”