Activation of C–F bonds α to C–C multiple bonds

Abstract

C-F bond activation has drawn a lot of attention in the past, and the case of C(sp3)-F bonds is particularly interesting as those are the strongest single bonds carbon makes with any other element. This Feature Article aims at highlighting our work and that of others on the successful approaches that led to the activation of such C-F bonds at benzylic, allylic, propargylic and allenylic positions, for both mono- and polyfluorides. We now hope that this will set ground for discussions, contribute to fostering new ideas, and thus help in pushing current frontiers further.

Vessel Effect in C–F Bond Activation Prompts Revised Mechanism and Reveals an Autocatalytic Glycosylation

“…[2][3][4][5][6][7][8][9] Mukaiyama pioneered the field of anomeric C-F bond activation in carbohydrate chemistry with the introduction of glycosyl fluorides as novel electrophiles in glycosylation chemistry [10] (Scheme 1) that has since become a commonly employed electrophile for catalytic glycosylations. [3] Often, C-F bonds are activated under either reductive or basic conditions, but recent years have seen a growing interest in C-F bond activation under acidic/neutral conditions enabled by hydrogen bonding (Scheme 1). [3] Often, C-F bonds are activated under either reductive or basic conditions, but recent years have seen a growing interest in C-F bond activation under acidic/neutral conditions enabled by hydrogen bonding (Scheme 1).…”

“…[1] In recent years, the activation of C(sp 3 )-F bonds has received considerable attention as the C(sp 3 )-F group has emerged as a useful electrophile with distinct reactivity. [2][3][4][5][6][7][8][9] Mukaiyama pioneered the field of anomeric C-F bond activation in carbohydrate chemistry with the introduction of glycosyl fluorides as novel electrophiles in glycosylation chemistry [10] (Scheme 1) that has since become a commonly employed electrophile for catalytic glycosylations. [11,12] Several other applications of C(sp 3 )-F bond activation have been developed, and significant highlights in this vast field of research have recently been reviewed in detail by Hamel and Paquin.…”

“…[11,12] Several other applications of C(sp 3 )-F bond activation have been developed, and significant highlights in this vast field of research have recently been reviewed in detail by Hamel and Paquin. [3] Often, C-F bonds are activated under either reductive or basic conditions, but recent years have seen a growing interest in C-F bond activation under acidic/neutral conditions enabled by hydrogen bonding (Scheme 1). Paquin and co-workers have developed methods for chemoselective benzylic-, [13][14][15][16][17] allylic- [13] and propargylic [18] C-F bond activation mediated through hydrogen bonding, reporting that the hydrogen fluoride developed during the reaction would function as an active catalyst, resulting in an autocatalytic kinetic profile.…”

Synthesis of Polycyclic Furan and Chromene Derivatives via Cascade Reactions Enabled by Cleavage of Multiple C(sp3)−F Bonds

“…Compared with more activated aromatic [21][22][23][24][25] or vinylic analogues, [26][27][28][29][30][31][32][33] selective aliphatic C(sp 3 )À F functionalization of unreactive perfluoroalkyl substance with multiple CÀ F bonds attached remote to π-system is relatively uncommon. [34][35][36][37][38][39][40][41][42][43][44][45][46][47] The successful realization of this challenging issue is complicated by several apparent factors (Scheme 1A). First, the high strength and activation barrier of CÀ F bond (BDE CÀ F = 500 � 50 kJ/ mol) result in chemical robustness of fluorocarbon in terms of thermodynamic stability and kinetic inertness.…”

Defluoroalkylation of sp3 C−F Bonds of Industrially Relevant Hydrofluoroolefins

“…[13][14][15] In contrast, methods for selective carboncarbon bond formation from vinylic trifluoromethyl groups are far less well advanced, likely due to the difficulty in controlling the reactivity of the adjacent C=C p-system. [16][17][18][19] Ito andc o-workers have reportedt he enantioselective defluoroalkylation of trifluoromethyl-substituted alkenes. [20] The key step in this report was the defluoroborylation of the substrateu sing ac hiral copper(I) catalyst.B oth racemic and enantioselective variants of this reactionh ave been widely studied.…”