Efficient Synthesis of α‐Trifluoromethyl Carboxylic Acids and Esters through Fluorocarboxylation of <i>gem</i>‐Difluoroalkenes

Yoo, Woo‐Jin; Kondo, Junpei; Rodríguez‐Santamaría, José A.; Nguyen, Thanh V. Q.; Kobayashi, Shū

doi:10.1002/anie.201902779

Cited by 54 publications

(25 citation statements)

References 54 publications

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“…However, only up to 56:44 er was achieved in Feng and Loh's catalytic system after examining a variety of chiral ligands. Furthermore, Kobayashi [9] and Jiang [10] demonstrated that α‐CF 3 carbanion intermediate could be intercepted by CO 2 or bromoalkyne, furnishing the α‐CF 3 ‐carboxylic acids or α‐CF 3 ‐halides, respectively (Scheme 1 b). In 2018, α‐CF 3 carbocation intermediate was report by Wang [11] and Hu, [12] which generated from gem ‐difluoroalkenes with a F + source and applied to aminofluorination and fluoro‐hydroxylation, respectively (Scheme 1 c).…”

Section: Methodsmentioning

confidence: 99%

Design and Synthesis of TY‐Phos and Application in Palladium‐Catalyzed Enantioselective Fluoroarylation ofgem‐Difluoroalkenes

Lin

Pan

et al. 2020

Angewandte Chemie

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The first example of highly enantioselective fluoroarylation of gem-difluoroalkenes with aryl halides is presented by using a new chiral sulfinamide phosphine (Sadphos) type ligand TY-Phos. N-Me-TY-Phos can be easily synthesized on a gram scale from readily available starting materials in three steps. Salient features of this work including readily available starting materials, good yields, high enantioselectivities as well as broad substrate scope make this approach very practical and attractive. Notably, the asymmetric synthesis of an analogue of a biologically active molecule is also reported. The gem-difluoroalkenes are increasingly being exploited as versatile fluorinated building blocks in organofluorine synthesis [1] via mono-defluorinative [2] or fluorine retentive [3] functionalization reactions. Over the past decade, by taking advantage of easily available gem-difluoroalkenes as reliable trifluoromethyl (CF 3) precursors, many chemists reported a conceptually novel protocol for the expedient synthesis of CF 3-containing molecules through an additional fluorine source via a radical pathway or an anion/ cation mechanism (Scheme 1),which are supplement to the typical trifluoromethylation reaction. [4] In 2014, Hu and co-workers demonstrated the formation of a-trifluoromethylated benzylsilver species from the reaction of gem-difluoroalkene with AgF for the first time, and which undergoes rapid C-Ag I bond homolysis in situ to afforded the a-CF 3 benzyl radical. [5] Recently, Feng et al. [6] reported a photoredox-coupled Fnucleophilic addition induced allylic alkylation of gemdifluoroalkenes via the a-CF 3 benzyl radical intermediate (Scheme 1 a). In contrast, the Feng and Loh group [7] and Malcolmson et al. [8] realized palladium-catalyzed fluorinative allylation and arylation of gem-difluoroalkenes via a-CF 3 carbanion intermediate, and the first attempt to palladiumcatalyzed asymmetric fluoroallylation of gem-difluoroalkenes Scheme 1. Trifluoromethylation of gem-difluoroalkenes.

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Section: Methodsmentioning

confidence: 99%

Design and Synthesis of TY‐Phos and Application in Palladium‐Catalyzed Enantioselective Fluoroarylation ofgem‐Difluoroalkenes

Lin

Pan

et al. 2020

Angewandte Chemie

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“…This strategy benefits from a reversible equilibrium as the addition of Freaction generates an ,,-trifluoromethyl anion 15, from which -fluoride elimination simply regenerates the gemdifluoroalkene, thus preventing the loss of substrate. [7][8][9][10][11][12][13][14][15] When using AgF, the metalated intermediate 17 can participate in Ag-or Pd-catalyzed processes in difunctionalization reactions (Scheme 2B). [16][17][18][19] Moreover, the use of electrophilic sources of fluorine, such as Selectfluor and NFSI can avoid anionic intermediates entirely (Scheme 2C).…”

Section: Two-electron Processesmentioning

confidence: 99%

Fluorine-Retentive Strategies for the Functionalization of gem-Difluoroalkenes

Sorrentino

Altman

2021

Synthesis

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gem-Difluoroalkenes are readily available fluorinated building blocks, and the fluorine-induced electronic perturbations of the alkenes enables a wide array of selective functionalization reactions. However, many reactions of gem-difluoroalkenes result in a net C–F functionalization to generate monofluorovinyl products or addition of F to generate trifluoromethyl-containing products. In contrast, fluorine-retentive strategies for the functionalization of gem-difluoroalkenes remain less generally developed, and is now becoming a rapidly developing area. This review will present the development of fluorine-retentive strategies including electrophilic, nucleophilic, radical, and transition metal catalytic strategies with an emphasis on key physical organic and mechanistic aspects that enable reactivities.

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“…This alternative route for synthesizing carboxylic acids could be employed with trifluoromethylated compounds [26,27]. These are an important group in the fluoro-alkyles group, and its carboxylic acid derivative has associated interest because it is a biologically active compound.…”

Section: Scheme 1 Electrochemical Carboxylation Processmentioning

confidence: 99%

Electrochemical Incorporation of Carbon Dioxide into Fluorotoluene Derivatives under Mild Conditions

2021

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One of the main challenges to combat climate change is to eliminate or reuse Carbon dioxide (CO2), the largest contributor to the greenhouse gases that cause global warming. It is also important to synthesize compounds through greener technologies in order to obtain more environmentally friendly solutions. This study describes the electrocarboxylation process of α,α,α-trifluorotoluene using different working electrodes (glassy carbon, silver and copper) and electrolytes (polar aprotic solvent and ionic liquid). Carboxylated compounds were obtained in the same way in both electrolytic medias with more than 80% conversion rates, high yields, good selectivity, and moderate efficiencies using silver and copper as cathodes in organic electrolytes and ionic liquids.

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Efficient Synthesis of α‐Trifluoromethyl Carboxylic Acids and Esters through Fluorocarboxylation of gem‐Difluoroalkenes

Cited by 54 publications

References 54 publications

Design and Synthesis of TY‐Phos and Application in Palladium‐Catalyzed Enantioselective Fluoroarylation ofgem‐Difluoroalkenes

Design and Synthesis of TY‐Phos and Application in Palladium‐Catalyzed Enantioselective Fluoroarylation ofgem‐Difluoroalkenes

Fluorine-Retentive Strategies for the Functionalization of gem-Difluoroalkenes

Electrochemical Incorporation of Carbon Dioxide into Fluorotoluene Derivatives under Mild Conditions

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