Synthesis of gem-Difluoroalkenes by Copper-catalyzed Regioselective Hydrodefluorination of 1-Trifluoromethylalkenes

Abstract

A copper-catalyzed regioselective hydrodefluorination of 1-trifluoromethylalkenes with hydrosilanes has been developed. The copper catalysis is compatible with several functional groups, including alkyl chloride, ether, ester, nitrile, and imide moieties, to form the corresponding gemdifluoroalkenes in good yields. Additionally, the asymmetric induction is also possible by using the chiral DTBM-SEGPHOS ligand, and the gem-difluoroalkene with the point chirality at the allylic position is obtained with high enantioselectivity.

Catalytic Enantioselective Allylic C–F Bond Functionalization

“…Very recently a single example of copper-catalyzed enantioselective hydrodefluorination of 1-trifluoromethylalkenes 25 has been presented by Hirano and Miura using chiral phosphine ligand 26 (Scheme 12). 18 In this transformation, polymethylhydrosiloxane (PMHS) was used as hydrogen source. The formation of copper-hydrogen species is the vital process for the hydrodefluorination of 1-trifluoromethylalkenes, which inserts into the C=C bond of substrates from the less sterically hindered side and then undergoes β-fluorine elimination to provide enantioenriched gem-difluoroalkenes 27 with high enantioselectivity.…”

Cu catalyzed [4 + 2] cycloaddition for the synthesis of highly substituted 3-fluoropyridines

“…In recent years, the defluorinative functionalization of the trifluoromethyl group has been shown to be advantageous for synthesizing a diverse range of fluorinated compounds. 14 The cleavages of the C–F bond are reported to be accomplished on the CF 3 group attached to alkenes, carbonyl derivatives and arenes, by using transition metal catalysis, 15 FLP 16 and Lewis acid mediated transformations 17 as well as photoredox catalysis. 18 Trifluoromethylated ketimine, as a CF 3 building block, 19 has been successfully applied in the asymmetric umpolung Michael addition 20 and Morita–Baylis–Hillman reactions.…”

Access to gem-Difluoroalkenes via Organic Photoredox-Catalyzed gem-Difluoroallylation of Alkyl Iodides

“…Recently, α-trifluoromethyl alkenes have been used as important reagents for the synthesis of gem -difluoroalkenes through an addition–elimination process . These conventional strategies include SN 2 ′-type reaction, which employed organometallics or strong base as the react partner, and transition metal (such as Ni, Cu, Fe, and Cr) catalyzed difluoroallylation (Scheme a) . Moreover, Zhou first developed an ideal alternative route to the synthesis of gem -difluoroalkenes via an Ir-photocatalyzed gem -difluoroallylation of α-trifluoromethyl alkenes with α-ketoacids or N -protected α-amino acids in 2016 .…”