Photocatalyzed Defluorinative Dichloromethylation of α-CF₃ Alkenes Using CHCl₃ as the Radical Source

Abstract

A visible-light-induced defluorinative dichloromethylation of α-CF3 alkenes was developed with cheap and readily accessible chloroform simultaneously as a dichloromethylation reagent and reaction medium, leading to the facile preparation of new polyhalogenated scaffolds. Notably, the change from CHCl3 to CDCl3 offers a straightforward pathway for accessing the deuterated analogues with excellent degrees of D incorporation. Mechanistic studies suggested the reaction underwent a radical addition of the dichloromethyl radical with alkenes, followed by sequential single-electron transfer and defluorination. This protocol features mild conditions, easy operation, facile scalability, and high efficiency, allowing convenient access to dichloronated gem-difluoroalkenes.

Photoinduced activation of alkyl chlorides

“…In 2022, Yang and co-workers 27 reported a visible-light-induced dichloromethylation of α-CF 3 alkenes using chloroform as the dichloromethyl radical source (Scheme 10). When the commercially available and inexpensive deuterated chloroform was used as the radical precursor, the reaction occurred smoothly and a series of structurally novel deuterium-containing difluorinated products could be obtained with good deuterium incorporation.…”

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

“…In this context, substantial efforts have been devoted to developing new methods to synthesize gem -difluoroalkenes. Recently, photocatalytic 11 and transition-metal-catalyzed 12 (Pd, Ni, Ti, Zn, and Cr) defluorinative cross-couplings of α-trifluoromethyl alkenes with various electrophiles or radical precursors have emerged as practical methods to access gem -difluoroalkenes through a radical to polar crossover mechanism (Scheme 1b). In contrast to the above-mentioned methods using strong nucleophiles as reagents, the latter reductive strategy realized the precise construction of C–C bonds from a series of electrophiles including N -hydroxyphthalimide (NHP) esters, organohalides, oxime esters, Katritzky salts, epoxides, acetals, ketones, and aldehydes through photo- or transition-metal-catalysis under mild reaction conditions (Scheme 1b).…”

Stereospecific Nickel-Catalyzed Cross-Electrophile Coupling Reaction of Alkyl Mesylates and Allylic Difluorides to Access Enantioenriched Vinyl Fluoride-Substituted Cyclopropanes

“…One strategy for the synthesis of complex fluorinated moieties involves cross-coupling (XC) or cross-electrophile coupling (XEC) reactions of perfluorinated starting materials where one C–F bond is cleaved and others remain . For example, trifluoromethyl alkenes undergo XEC reactions, providing access to highly substituted difluorinated alkenes (Scheme a). − These reactions typically employ a radical precursor and proceed via radical addition to the alkene followed by radical-polar crossover and β-fluoride elimination. Coupling reactions that use allylic geminal difluorides are less developed. , Hayashi and co-workers have developed an enantioselective Suzuki XC reaction of allylic difluorides for the synthesis of complex α-fluoro,α,β-unsaturated carbonyls (Scheme b) .…”

“… 3 For example, trifluoromethyl alkenes undergo XEC reactions, providing access to highly substituted difluorinated alkenes ( Scheme 1 a). 4 − 7 These reactions typically employ a radical precursor and proceed via radical addition to the alkene followed by radical-polar crossover and β-fluoride elimination. Coupling reactions that use allylic geminal difluorides are less developed.…”