Copper‐Catalyzed Trifluoromethylation Reactions

Kananovich, Dzmitry G.

doi:10.1002/9783527826445.ch17

Cited by 6 publications

(4 citation statements)

References 141 publications

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“…Consequently, in the past decade, a wide variety of methods including transition-metal-catalyzed cross-coupling reactions or C–H trifluoromethylation that are capable of late-stage incorporation of the trifluoromethyl group into (hetero)arenes have emerged . More specifically, copper-mediated/-catalyzed trifluoromethylation of aryl halides represents one of the most practical approaches for the construction of the trifluoromethylated (hetero)arene units, largely ascribing to the copper catalyst’s high reactivity, low cost, mild conditions, and broad functional group compatibility …”

Section: Introductionmentioning

confidence: 99%

Mechanistic Insight into Copper-Mediated Trifluoromethylation of Aryl Halides: The Role of CuI

Liu

Jin

et al. 2021

J. Am. Chem. Soc.

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The synthesis, characterization, and reactivity of key intermediates [Cu(CF 3 )(X)] − Q + (X = CF 3 or I, Q = PPh 4 ) in copper-mediated trifluoromethylation of aryl halides were studied. Qualitative and quantitative studies showed [Cu(CF 3 ) 2 ] − Q + and [Cu(CF 3 )(I)] − Q + were not highly reactive. Instead, a much more reactive species, ligandless [CuCF 3 ] or DMF-ligated species [(DMF)CuCF 3 ], was generated in the presence of excess CuI. On the basis of these results, a general mechanistic map for CuIpromoted trifluoromethylation of aryl halides was proposed. Furthermore, on the basis of this mechanistic understanding, a HOAc-promoted protocol for trifluoromethylation of aryl halides with [Ph 4 P] + [Cu(CF 3 ) 2 ] − was developed.

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Section: Introductionmentioning

confidence: 99%

Mechanistic Insight into Copper-Mediated Trifluoromethylation of Aryl Halides: The Role of CuI

Liu

Jin

et al. 2021

J. Am. Chem. Soc.

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“…There are three main methods for preparing TFMP derivatives: chlorine/fluorine exchange using trichloromethylpyridine; construction of a pyridine ring from a trifluoromethyl-containing building block; or direct introduction of a trifluoromethyl group using a trifluoromethyl active species such as trifluoromethyl copper, which undergoes substitution reactions with bromoand iodopyridines. 11) The first two methods are currently the most commonly used; therefore, the discussion below focuses on those two methods.…”

Section: Synthesis Of Tfmp Derivativesmentioning

confidence: 99%

“…One structural characteristic of picoxystrobin is a pyridine ring in which the 6-position is substituted with a trifluoromethyl group. Two procedures for the preparation of 6-(trifluoromethyl) pyridin-2(1H)-one (11) have been reported: a cyclocondensation method starting from (E)-4-ethoxy-1,1,1trifluorobut-3-en-2-one and direct fluorination of 2-picoline through a chlorine/fluorine exchange reaction, as shown in Scheme 19. [77][78][79] Scheme 19.…”

Section: Fungicidementioning

confidence: 99%

Synthesis and application of trifluoromethylpyridines as a key structural motif in active agrochemical and pharmaceutical ingredients

et al. 2021

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Herein, we provide a brief overview of the synthesis and applications of trifluoromethylpyridine (TFMP) and its derivatives in the agrochemical and pharmaceutical industries. Currently, the major use of TFMP derivatives is in the protection of crops from pests. Fluazifopbutyl was the first TFMP derivative introduced to the agrochemical market, and since then, more than 20 new TFMP-containing agrochemicals have acquired ISO common names. Several TFMP derivatives are also used in the pharmaceutical and veterinary industries; five pharmaceutical and two veterinary products containing the TFMP moiety have been granted market approval, and many candidates are currently undergoing clinical trials. The biological activities of TFMP derivatives are thought to be due to the combination of the unique physicochemical properties of the fluorine atom and the unique characteristics of the pyridine moiety. It is expected that many novel applications of TFMP will be discovered in the future.

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“…However, improvement in this area, either in terms of discovering suitable reaction conditions or accessing novel CF 3 ‐bearing molecules, has been extensively pursued (Alonso, de Marigorta, Rubiales, & Palacios, 2015; Zhu et al., 2014). Among various protocols developed, copper‐catalyzed/mediated trifluoromethylation has been scrutinized widely and found to be exceptionally effective (Kananovich, 2020; Li, Zhang, Song, & Ma, 2018).…”

Section: Introductionmentioning

confidence: 99%

Microwave Assisted Cu‐Mediated Trifluoromethylation of Pyrimidine Nucleosides

Mangla

Sanghvi²,

Prasad

2021

Current Protocols

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Trifluoromethylated nucleosides, such as trifluridine, have widespread applications in pharmaceuticals as anticancer and antiviral agents. However, site‐selective addition of a trifluoromethyl group onto a nucleobase typically requires either inconvenient multi‐step synthesis or expensive trifluoromethylation reagents, or results in low yield. This article describes a simple, scalable, and high‐yielding protocol for late‐stage direct trifluoromethylation of pyrimidine nucleosides via a microwave‐irradiated pathway. First, 5‐iodo pyrimidine nucleosides undergo complete benzoylation to obtain N3‐benzoyl‐3',5'‐di‐O‐benzoyl‐5‐iodo‐pyrimidine nucleosides as key precursors. Next, trifluoromethylation is carried out under both conventional and microwave heating using an inexpensive and commercially accessible Chen's reagent, i.e., methyl fluorosulfonyldifluoroacetate, to produce N3‐benzoyl‐3',5'‐di‐Obenzoyl‐5‐trifluoromethyl‐pyrimidine nucleosides. The microwave‐assisted transformation accentuates its simplicity, mild reaction conditions, and dominance, providing a facile route to access trifluoromethylation. Finally, the envisioned 5‐trifluoromethyl pyrimidine nucleosides are obtained by a routine debenzoylation procedure. This concludes a convenient three‐step synthesis to obtain trifluridine and its 2'‐modified analogs on a gram scale with consistently high yields, starting from their respective iodo‐precursors, and requires only one chromatographic purification at the trifluoromethylation step. Furthermore, this operationally simple protocol can be utilized as a definitive methodology to produce various other trifluoromethylated therapeutics. © 2021 Wiley Periodicals LLC. Basic Protocol: Synthesis of 5‐trifluoromethyl pyrimidine nucleosides 4a‐c Alternate Protocol: Conventional trifluoromethylation: Synthesis of N3‐benzoyl‐3',5'‐di‐O‐benzoyl‐5‐trifluoromethyl pyrimidine nucleosides (3a‐c)

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Copper‐Catalyzed Trifluoromethylation Reactions

Cited by 6 publications

References 141 publications

Mechanistic Insight into Copper-Mediated Trifluoromethylation of Aryl Halides: The Role of CuI

Mechanistic Insight into Copper-Mediated Trifluoromethylation of Aryl Halides: The Role of CuI

Synthesis and application of trifluoromethylpyridines as a key structural motif in active agrochemical and pharmaceutical ingredients

Microwave Assisted Cu‐Mediated Trifluoromethylation of Pyrimidine Nucleosides

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