Lewis Acid Promoted Single C–F Bond Activation of the CF₃ Group: S_N1′‐Type 3,3‐Difluoroallylation of Arenes with 2‐Trifluoromethyl‐1‐alkenes

Abstract

Activation of the sp C-F bond in 2-trifluoromethyl-1-alkenes was accomplished through treatment with a Lewis acid. In the presence of an equimolar amount of EtAlCl , the (trifluoromethyl)alkenes readily underwent an S 1'-type reaction with arenes through a Friedel-Crafts-type mechanism via elimination of a fluoride ion to afford 3,3-difluoroallylated arenes in good yields. This selective activation of one C-F bond of the CF group provides a synthetic method for accessing biologically and synthetically important 1,1-difluoro-1-alkenes.

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

“…In an alternative approach to the common S N 2′ reaction of 1‐CF 3 ‐alkenes with nucleophiles, Ichikawa presented for the first time a Lewis acid mediated reaction, following an S N 1′ mechanism (Scheme ) . Various 1‐CF 3 alkenes 72 were reacted with Et 2 AlCl in the presence of p ‐xylene to afford the corresponding 3,3‐difluoroallylcompounds 73 .…”

“…In an alternative approach to the commonS N 2' reaction of 1-CF 3 -alkenes with nucleophiles, Ichikawa presented for the first time aL ewis acid mediated reaction, following an S N 1' mechanism (Scheme 15). [36] Various 1-CF 3 alkenes 72 were reacted with Et 2 AlCl in the presence of p-xylene to afford the corresponding 3,3-difluoroallylcompounds 73.O ther Lewis acids gave lower yields (AlCl 3 or ZrCl 4 )o rdid not reacta ta ll (BF 3 ,T iCl 4 ). The fluorine stabilized allylic CF 2 cation 74 was proposed as intermediate, which could even be attacked by nonmetallated nucleophiles, as shown in this case with several aromatic compounds through aF riedel-Crafts type mechanism.…”

Photoredox‐Coupled F‐Nucleophilic Addition: Allylation of gem‐Difluoroalkenes

“…[3] Aside from ah andful of CF 3 -radical-based functionalizations of structurally elaborated styrene derivatives, [4] these molecules could be created either by direct trifluoromethylation of aliphatic skeletons [5] or through crosscoupling using a-CF 3 -derived precursors (Scheme 1a). [6,[12][13][14][15][16] With Lisp ioneering work on trifluoromethylation of alkyl radicals using Grushinsreagent, [7] thegroups of MacMillan, [8] Cook, [9] and Liu, [10] developed decarboxylative and benzylic C À Ht rifluoromethylation protocols,a lthough the employment of expensive CF 3 reagents,aswell as restricted substrate scope,are still concerns.…”

“…Making use of trifluoroethylarene derivatives as building blocks also allows smooth construction of target molecules.In this regard, the manipulation of a-CF 3 -substituted benzylic cation, [11] anion, [12] and radical [13] intermediates were extensively explored, with elegant works from the groups of Moran, Tr edwell, Molander, Hu, and Fu constituting am ajor break-through in this territory.D espite these advances,r eactions proceeding via a-CF 3 -substituted benzylic cation or anion intermediates themselves possess innate limitations because of stability problems. [14] By contrast, a-CF 3 -substituted benzylic radical intermediates,a lbeit nontrivial in their generation, are comparatively more tractable and devoid of either substrate deactivation or degradation by b-F elimination, [15] and leaves ample room for potential elaboration.…”

Aromaticity‐promoted C−F Bond Activation in Rhodium Complex: A Facile Tautomerization

“…[6] Lately,I chikawa and coworkers demonstratedt he Lewis acid promoted single C-F bond activation in 2-trifluoromethyl-1-alkenes, which is as elec-tive activation of one CÀFb ond of the CF 3 group. [7] Ar eaction about CÀFb ond cleavage enabled redox-neutral [4+ +1] annulation via CÀHb ond activation was also reported by Loh's group, and the two-fold C-F bond cleavage led to am igration of carbon-carbon triple bond. [8] On the other hand, recent studies showt hat the formation of the h 4 -pentamethylcyclopentadiene (Cp*H) motif upon reductiona nd protonation of the precatalyst [Cp*Rh] complexes.…”