Rhodium-Catalyzed Asymmetric Arylation/Defluorination of 1-(Trifluoromethyl)alkenes Forming Enantioenriched 1,1-Difluoroalkenes

Abstract

The reaction of 1-(trifluoromethyl)alkenes (CF3CH=CHR) with arylboroxines (ArBO)3 in the presence of a chiral diene-rhodium catalyst gave high yields of chiral 1,1-difluoroalkenes (CF2=CHC*HArR) with high enantioselectivity (≥95% ee). The reaction is assumed to proceed through β-fluoride elimination of a β,β,β-trifluoroalkylrhodium intermediate that is generated by arylrhodation of the 1-(trifluoromethyl)alkene.

Picking One out of Three: Selective Single C−F Activation in Trifluoromethyl Groups

“…[28] In 2016, Hayashi showed the efficient rhodium-catalyzed asymmetricd efluorinative arylation of b-substituted 1-CF 3 alkenes 28 using arylboroxines 29 and ac hiral diene-rhodium complex based on the ferrocenyl diene ligand 30 (Scheme 9). [29] The chiral 1,1-difluoroalkenes 31 were obtained in high yields and excellent enantioselectivity. The reaction is compatible with several1 -CF 3 -alkenes containing amine, ester,a lcohol or silyl groupsa nd allows the introductionofvarious aryl groups, including 4-bromo or 4-CF 3 substituents.…”

“…A rhodium(I) catalysed reaction of 1‐CF 3 alkenes with arylborates yielding achiral β,β‐difluorostyrene derivatives was initially reported by Murakami in 2008 . In 2016, Hayashi showed the efficient rhodium‐catalyzed asymmetric defluorinative arylation of β‐substituted 1‐CF 3 alkenes 28 using arylboroxines 29 and a chiral diene‐rhodium complex based on the ferrocenyl diene ligand 30 (Scheme ) . The chiral 1,1‐difluoroalkenes 31 were obtained in high yields and excellent enantioselectivity.…”

Copper-Catalyzed Asymmetric Defluoroborylation of 1-(Trifluoromethyl)Alkenes

“…[2][3][4][5][6] Although impressive progress has been made in the synthesis of gem-difluoroalkenes in recent years, for example, the classical Wittig olefination and Julia-Kocienski reaction, some issues remain unresolved. [7][8][9][10][11][12][13][14][15][16][17][18] First, most traditional approaches require strong bases, which leads to a limited substrate scope and low efficiency; second, the a position of a gem-difluorovinyl group in a drug candidate is usually a chiral carbon center, and the induction of enantioselectivity at this position is still challenging 19 ; third, the rapid and efficient installation of a range of functional groups such as hydroxyl, amino, and alkyl substituents to a position of a difluorovinyl group is in high demand. On the other hand, a-chiral boronate-substituted compounds are an important family of target molecules, because the C-B linkage provides an extremely useful stereogenic center.…”

Transition‐Metal‐Mediated and ‐Catalyzed C−F Bond Activation by Fluorine Elimination

“…Chemie difluoroalkenes.Huang and Hayashi reported the asymmetric arylation of 1-trifluoromethyl-1-alkenes with arylboroxines by allylic C À Fb ond activation, which is catalyzed by aR h I catalyst bearing ac hiral diene ligand (Scheme 12 b). [28] Most recently,C ao and co-workers reported the Cu I -catalyzed alkylation of a-(trifluoromethyl)styrenes with tert-alkylmagnesium reagents (Scheme 13). [29] Theg roup of Ogoshi and Ohashi achieved Cu I -mediated arylation of the vinylic CÀFbond of tetrafluoroethylene with arylboronates to afford trifluorostyrenes (Scheme 14 a).…”