64841-37-8Relevant academic research and scientific papers
Copper-Catalyzed Late-Stage Benzylic C(sp3)–H Trifluoromethylation
Xiao, Haiwen,Liu, Zhonglin,Shen, Haigen,Zhang, Benxiang,Zhu, Lin,Li, Chaozhong
, p. 940 - 949 (2019)
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.
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.).
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.
Copper-Catalyzed Trifluoromethylation of Alkyl Bromides
Kornfilt, David J.P.,Macmillan, David W.C.
supporting information, p. 6853 - 6858 (2019/05/10)
Copper oxidative addition into organohalides is a challenging two-electron process. In contrast, formal oxidative addition of copper to C sp2 carbon-bromine bonds can be accomplished by employing latent silyl radicals under photoredox conditions. This novel paradigm for copper oxidative addition has now been applied to a Cu-catalyzed cross-coupling of C sp3-bromides. Specifically, a copper/photoredox dual catalytic system for the coupling of alkyl bromides with trifluoromethyl groups is presented. This operationally simple and robust protocol successfully converts a variety of alkyl, allyl, benzyl, and heterobenzyl bromides into the corresponding alkyl trifluoromethanes.
Copper-promoted reductive coupling of aryl iodides with 1,1,1-trifluoro-2-iodoethane
Xu, Song,Chen, Huan-Huan,Dai, Jian-Jun,Xu, Hua-Jian
supporting information, p. 2306 - 2309 (2014/05/20)
An efficient Cu-promoted reductive coupling of aryl iodides with 1,1,1-trifluoro-2-iodoethane has been developed. This reaction could occur in good yields under milder conditions as compared with previous studies. The reaction tolerated nitro, formyl, ester, ether, carbonyl, sulfonyl, and even azo groups.
