1099597-89-3Relevant academic research and scientific papers
Copper-Mediated Trifluoromethylation of Benzylic Csp3?H Bonds
Paeth, Matthew,Carson, William,Luo, Jheng-Hua,Tierney, David,Cao, Zhi,Cheng, Mu-Jeng,Liu, Wei
, p. 11559 - 11563 (2018)
Trifluoromethyl-containing compounds play a significant role in medicinal chemistry, materials and fine chemistry. Although direct C?H trifluoromethylation has been achieved on Csp2?H bonds, direct conversion of Csp3?H bonds to Csp3?CF3 remains challenging. We report herein an efficient protocol for the selective trifluoromethylation of benzylic C?H bonds. This process is mediated by a combination CuIII?CF3 species and persulfate salts. A wide range of methylarenes can be selectively trifluoromethylated at the benzylic positions. A combination of experimental and theoretical mechanistic studies suggests that the reaction involves a radical intermediate and a CuIII?CF3 species as the CF3 transfer reagent.
Using Chlorotrifluoroethane for Trifluoroethylation of (Hetero)aryl Bromides and Chlorides via Nickel Catalysis
Li, Xuefei,Gao, Xing,He, Chun-Yang,Zhang, Xingang
supporting information, p. 1400 - 1405 (2021/02/20)
A nickel-catalyzed reductive cross-coupling between industrial chemical CF3CH2Cl and (hetero)aryl bromides and chlorides has been reported. The reaction is synthetically simple without the preparation of arylmetals and exhibits high functional group tolerance. The utility of this protocol has been demonstrated by the late-stage modification of pharmaceuticals, providing a facile route for medicinal chemistry.
Preparation method of trifluoroethyl compounds
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Paragraph 0048-0051; 0056-0058; 0059; 0060; 0061, (2020/01/25)
The invention discloses a preparation method of trifluoroethyl compounds. The trifluoroethyl compounds are synthesized by directly using cheap and abundant industrial raw materials 2-chloro-1,1,1-trifluoroethane and halogenated substances as raw materials by stirring in a polar solvent under the action of a catalytic system using cheap and an easily available alkali metal nickel salt catalyst anda pyridine ligand for reacting under mild reaction conditions of 50-90 DEG C for 12-24 hours, and the efficient introduction of the trifluoroethyl groups to aromatic ring groups or heterocyclic aryl groups can be realized to prepare the trifluoroethyl compounds. The method has the advantages of mild reaction conditions, simple operation, low cost of raw materials and catalysts, good compatibilityof substrate functional groups, easy expansion of reaction scale, simple separation of products and suitability for industrial production.
Dehydroxylative Trifluoromethylthiolation, Trifluoromethylation, and Difluoromethylation of Alcohols
Zhang, Wei,Lin, Jin-Hong,Wu, Wenfeng,Cao, Yu-Cai,Xiao, Ji-Chang
supporting information, p. 169 - 172 (2020/01/03)
CF3S, CF3 and HCF2 groups have been identified as valuable functionalities for drug development. Despite significant accomplishments in the trifluoromethylthiolation, trifluoromethylation and difluoromethylation reactions, directly converting common functional groups into CF3S, CF3 or HCF2 groups is still highly desirable. Described here is the dehydroxylative trifluoromethylthiolation, trifluoromethylation and difluoromethylation of alcohols promoted by a R3P/ICH2CH2I system. All of these dehydroxylative reactions were achieved under mild conditions via the activation of the hydroxyl group by the R3P/ICH2CH2I system. A wide substrate scope and good functional group tolerance were observed.
Nickel-Catalyzed Direct Trifluoroethylation of Aryl Iodides with 1,1,1-Trifluoro-2-Iodoethane via Reductive Coupling
Li, Han,Sheng, Jie,Liao, Guang-Xu,Wu, Bing-Bing,Ni, Hui-Qi,Li, Yan,Wang, Xi-Sheng
supporting information, p. 5363 - 5367 (2020/10/19)
A nickel-catalyzed direct trifluoroethylation of aryl iodides with an industrial raw material CF3CH2I has been developed, demonstrating high efficiency, excellent functional-group compatibility, especially with large sterically hindered groups. The key to success is the combination of nickel with readily available nitrogen and phosphine ligands. The powerful potential of this strategy is further demonstrated by the late-stage modification of several derived bioactive molecules. (Figure presented.).
Copper-Catalyzed Late-Stage Benzylic C(sp3)–H Trifluoromethylation
Xiao, Haiwen,Liu, Zhonglin,Shen, Haigen,Zhang, Benxiang,Zhu, Lin,Li, Chaozhong
supporting information, p. 940 - 949 (2019/04/10)
Direct trifluoromethylation of C(sp3)–H bonds, especially in late stages, remains a formidable challenge. Herein, we describe the copper-catalyzed benzylic C(sp3)–H trifluoromethylation. With Cu(I) or Cu(II) as the catalyst, (bpy)Zn(CF3)2 (bpy = 2,2′-bipyridine) as the CF3 source, and NFSI (or Selectfluor) as the oxidant, site-selective benzylic C(sp3)–H trifluoromethylation is successfully implemented in high efficiency under mild conditions. The protocol not only exhibits broad substrate scope and wide functional-group compatibility but also allows efficient late-stage C(sp3)–H trifluoromethylation of natural products or drug derivatives. The introduction of trifluoromethyl groups into organic molecules is of paramount importance in pharmaceuticals and agrochemicals because of their profound effect on properties such as lipophilicity, permeability, and metabolic stability. However, direct C(sp3)–H trifluoromethylation, which is most atom economical, remains a formidable challenge, and only a few examples with limited substrate scope and low to moderate efficiency have been reported to date. In this article, we introduce the copper-catalyzed benzylic C(sp3)–H trifluoromethylation with the easily available (bpy)Zn(CF3)2 complex as the CF3 source. This unprecedented protocol not only exhibits a high efficiency and broad substrate scope but also allows the late-stage trifluoromethylation of bioactive molecules or natural product derivatives. Because the procedure is operationally simple and the conditions are mild, the method should find immediate application in the synthesis of important trifluoromethylated molecules. Trifluoromethylated molecules are of paramount importance in pharmaceuticals and agrochemicals, but methods of making them by direct C(sp3)–H trifluoromethylation are extremely rare. In this issue of Chem, Li and coworkers describe a copper-catalyzed late-stage benzylic C–H trifluoromethylation with broad substrate scope and functional-group tolerance. The reaction may serve the late-stage modification of drug candidates.
Exploiting the trifluoroethyl group as a precatalyst ligand in nickel-catalyzed Suzuki-type alkylations
Yang, Yi,Zhou, Qinghai,Cai, Junjie,Xue, Teng,Liu, Yingle,Jiang, Yan,Su, Yumei,Chung, Lungwa,Vicic, David A.
, p. 5275 - 5282 (2019/05/29)
We report herein the exploitment of the partially fluorinated trifluoroethyl as precatalyst ligands in nickel-catalyzed Suzuki-type alkylation and fluoroalkylation coupling reactions. Compared with the [LnNiII(aryl)(X)] precatalysts, the unique characters of bis-trifluoroethyl ligands imparted precatalyst [(bipy)Ni(CH2CF3)2] with bench-top stability, good solubilities in organic media and interesting catalytic activities. Preliminary mechanistic studies reveal that an eliminative extrusion of a vinylidene difluoride (VDF, CH2CF2) mask from [(bipy)Ni(CH2CF3)2] is a critical step for the initiation of a catalytic reaction.
Aqueous Benzylic C-H Trifluoromethylation for Late-Stage Functionalization
Guo, Shuo,AbuSalim, Deyaa I.,Cook, Silas P.
supporting information, p. 12378 - 12382 (2018/10/05)
The installation of trifluoromethyl groups has become an essential step across a number of industries such as agrochemicals, drug discovery, and materials. Consequently, the rapid introduction of this critical functional group in a predictable fashion would benefit current practitioners in those fields. This communication describes a mild trifluoromethylation of benzylic C-H bonds with high selectivity for the least hindered hydrogen atom. The reaction provides monotrifluoromethylation and proceeds in an environmentally friendly acetone/water solvent system. The method can be used to install benzylic trifluoromethyl groups on highly functionalized drug molecules.
Silver-Catalyzed Decarboxylative Trifluoromethylation of Aliphatic Carboxylic Acids
Tan, Xinqiang,Liu, Zhonglin,Shen, Haigen,Zhang, Pei,Zhang, Zhenzhen,Li, Chaozhong
supporting information, p. 12430 - 12433 (2017/09/25)
The silver-catalyzed decarboxylative trifluoromethylation of aliphatic carboxylic acids is described. With AgNO3 as the catalyst and K2S2O8 as the oxidant, the reactions of aliphatic carboxylic acids with (bpy)C
Trifluoromethylation of Alkyl Radicals in Aqueous Solution
Shen, Haigen,Liu, Zhonglin,Zhang, Pei,Tan, Xinqiang,Zhang, Zhenzhen,Li, Chaozhong
supporting information, p. 9843 - 9846 (2017/08/02)
The copper-mediated trifluoromethylation of alkyl radicals is described. The combination of Et3SiH and K2S2O8 initiates the radical reactions of alkyl bromides or iodides with BPyCu(CF3)3 (BPy = 2,2′-bipyridine) in aqueous acetone at room temperature to afford the corresponding trifluoromethylation products in good yield. The protocol is applicable to various primary and secondary alkyl halides and exhibits wide functional group compatibility. A mechanism involving trifluoromethyl group transfer from Cu(II)-CF3 intermediates to alkyl radicals is proposed.
