Transition-metal-catalyzed C-H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

Abstract

The last decade has witnessed the emergence of innovative synthetic tools for the synthesis of fluorinated molecules. Among these approaches, the transition-metal-catalyzed functionalization of various scaffolds with a panel of fluorinated groups (XR_F, X = S, Se, O) offered straightforward access to high value-added compounds. This review will highlight the main advances made in the field with the transition-metal-catalyzed functionalization of C(sp²) and C(sp³) centers with SCF₃, SeCF₃, or OCH₂CF₃ groups among others, by C-H bond activation. The scope and limitations of these transformations are discussed in this review.

Keywords: C–H bond activation; emergent fluorinated groups; homogeneous catalysis; organofluorine chemistry; palladium; synthetic method.

Scheme 1

Transition-metal-catalyzed C–XR_F bond formation by C–H bond activation: an overview.

Scheme 2

Cu(OAc)₂-promoted mono- and ditrifluoromethylthiolation of benzamide derivatives derived from 8-aminoquinoline reported by the group of Daugulis [114].

Scheme 3

Trifluoromethylthiolation of azacalix[1]arene[3]pyridines using copper salts and a nucleophilic SCF₃ source reported by Wang and co-workers [100]. ^aA mixture of CHCl₃/MeOH 1:1 was used as solvent.

Scheme 4

Working hypothesis for the palladium-catalyzed C–H trifluoromethylthiolation reaction.

Scheme 5

Trifluoromethylthiolation of 2-arylpyridine derivatives and analogs by means of palladium-catalyzed C–H activation reported by the group of Shen [117]. ^a6 equiv of I were used at 150 °C for 24 h. ^bThe reaction was conducted at 150 °C for 24 h.

Scheme 6

C(sp²)–SCF₃ bond formation by Pd-catalyzed C–H bond activation using AgSCF₃ and Selectfluor^® as reported by the group of Huang [119]. ^a20 equiv of Cl₂CHCOOH were used instead of AcOH.

Scheme 7

Palladium-catalyzed ortho-trifluoromethylthiolation of 2-arylpyridine derivatives reported by the group of Ye and Liu [120].

Scheme 8

Palladium-catalyzed ortho-trifluoromethylthiolation of 2-arylpyridine and analogs reported by Anbarasan [121]. ^aThe reaction was conducted at 120 °C using 1.1 equiv of Billard reagent IV (R = Me).

Scheme 9

Mono- and ditrifluoromethylthiolation of benzamide derivatives derived from 8-aminoquinoline using PdCl₂ as catalyst reported by Besset and co-workers [106]. ^a2.2 equiv of the fluorinated source V were used.

Scheme 10

Regioselective Cp*Rh(III)-catalyzed directed trifluoromethylthiolation reported by the group of Li [123]. Cp* = pentamethylcyclopentadienyl.

Scheme 11

Cp*Co(III)-catalyzed ortho-trifluoromethylthiolation of 2-phenylpyridine and 2-phenylpyrimidine derivatives reported by Wang and co-workers [124]. ^aCH₂Cl₂ was used as solvent.

Scheme 12

Cp*Co(III)-catalyzed ortho-trifluoromethylthiolation of 2-phenylpyridine and 6-phenylpurine derivatives described by Yoshino and Matsunaga [125]. ^aWithout AgSbF₆. ^b2.0 equiv of VII, 10 mol % of AgOAc and 30 mol % of Gd(OTf)₃ were used instead of AgSbF₆.

Scheme 13

Diastereoselective trifluoromethylthiolation of acrylamide derivatives derived from 8-aminoquinoline using PdCl₂ reported by Bouillon and Besset [104,106]. ^a20 mol % of PdCl₂ and 2.0 equiv of SCF₃ source V were used for 36 h. ^bThe reaction was conducted with 30 mol % of PdCl₂ and 2.0 equiv of reagent V were used.

Scheme 14

C(sp³)–SCF₃ bond formation on aliphatic amide derivatives derived from 8-aminoquinoline by palladium-catalyzed C–H bond activation described by Besset and co-workers [126]. Product 32d was contaminated with 10% of an inseparable impurity.

Scheme 15

Regio- and diastereoselective difluoromethylthiolation of acrylamides under palladium catalysis reported by He and Pan [137].

Scheme 16

Palladium-catalyzed (ethoxycarbonyl)difluoromethylthiolation reaction of 2-(hetero)aryl and 2-(α-aryl-vinyl)pyridine derivatives reported by Besset [138].

Scheme 17

Pd(II)-catalyzed trifluoromethylselenolation of benzamides derived from 5-methoxy-8-aminoquinoline reported by the group of Billard [139]. ^aThe yields given are the sum of the yields of mono- and ditrifluoromethylselenolated products.

Scheme 18

Pd(II)-catalyzed trifluoromethylselenolation of acrylamide derivatives derived from 5-methoxy-8-aminoquinoline reported by the groups of Magnier and Billard [140]. ^aMicrowave, 100 °C, 1 h. ^b70 °C for 16 h. ^c20 mol % of Pd(CH₃CN)₂(Cl)₂, 100 °C for 24 h.

Scheme 19

Transition-metal-catalyzed dehydrogenative 2,2,2-trifluoroethoxylation of (hetero)aromatic derivatives by C–H bond activation [149]. ^aCF₃CH₂OH was used as solvent. ^bPd cat. = [Pd(μ-κ¹-OAc)(κ²-N,C₁₀-benzo[h]quinoline)]₂. ^c5 equiv of CF₃CH₂OH. ^d15 equiv of CF₃CH₂OH. ^e50 equiv of CF₃CH₂OH. ^fCF₃CH₂OH or (CF₃)₂CHOH was used as solvent with o-chlorotoluene with a ratio of 1:1. AdCOOH = adamantanecarboxylic acid, DMAP = 4-(dimethylamino)pyridine, OR_F = OCH₂CF₃.

Scheme 20

Pd(II)-catalyzed ortho-2,2,2-trifluoroethoxylation of N-sulfonylbenzamides reported by the group of Ji and Li [150]. ^a50 °C. ^b15 equiv TFA. ^c5 equiv TFA. ^dN-acetylglycine (60 mol %). Ns: 4-nitrobenzenesulfonyl.

Scheme 21

Pd(II)-catalyzed selective 2,2,2-trifluoroethoxylation and other fluoroalkoxylations of naphthalene sulfoxide derivatives reported by the group of Yorimitsu [169]. ^a80 °C for 1 h. ^bR_FOH/AcOH 1:7.

Scheme 22

Pd(II)-catalyzed selective ortho-2,2,2-trifluoroethoxylation of benzaldehyde derivatives by means of the transient directing group strategy as reported by the group of Wang [153].

Scheme 23

Pd(II)-catalyzed selective ortho-2,2,2-trifluoroethoxylation (and other fluoroalkoxylations) of benzaldehyde derivatives via the assistance of a transient directing group reported by the group of Sun and Wang [183].

Scheme 24

Pd(II)-catalyzed selective 2,2,2-trifluoroethoxylation of aliphatic amides using a bidentate directing group reported by the groups of Chen [71] and Shi [192].