Ruthenium-Catalyzed Ligand-Enabled Regiodivergent Difluoroallylation of Aryl C–H Bonds

Abstract

The gem-difluoroallyl group is a sought-after structural motif commonly found in pharmaceutical compounds. Despite its appeal, achieving a controlled synthesis of both α,αand γ,γ-difluoroallylated compounds has proven to be a challenging task. This study presents a new approach to difluoroallylation, which utilizes a regiodivergent C−H bond reaction catalyzed by ruthenium catalysis. This method enables the meta and ortho C−H α,αand ortho C−H γ,γ-difluoroallylation of arenes using 3-bromo-3,3difluoropropenes.

Ruthenium-Catalyzed Difunctionalization of Vinyl Cyclopropanes for Double m-C(sp2)–H/C-5(sp3)–H Functionalization

“…Meanwhile, ruthenium-catalyzed m -(sp 2 )-H functionalization has attracted a great deal of attention. Ackermann, Li, Zhang, and others have made appreciable progress in this field. Through detailed mechanistic studies, it has been confirmed that the ruthenium-catalyzed remote transformation operates via the distinctive mechanism of SET .…”

Stereoselective Synthesis of Multisubstituted Alkenes via Ruthenium-Catalyzed Remote Migration Arylation of Nonactivated Olefins

“…Ruthenium catalysis has made some progress in the construction of multisubstituted alkenes . Some of these representative figures were Krische, Ackermann, Zhang, Li, and others . In 2005, Inoue developed ruthenium-catalyzed arylation of 2-alkenylpyridines with aryl bromides, affording Z products exclusively (Scheme B).…”

Difluoromethylene insertion into fluoroalkyl copper complexes

“…1B). The synthetic methods of difluoromethylene compounds are relatively abundant, including the deoxyfluorination of ketones, 10 the nucleophilic transformation of difluoroenolates 11–13 and related nucleophiles, 14,15 regioselective difluoroallylation, 16–20 the addition of difluoroalkyl radical, 21–23 and the transfer of difluorocarbene. 24,25 The synthesis of tetrafluoroethylene bridged compounds has been achieved by the double deoxyfluorination of 1,2-diketone species; however, the reaction requires a large amount of corrosive fluorination reagents.…”