Conspectus The trifluoromethyl group is widely prevalent in many pharmaceuticals and agrochemicals because its incorporation into drug candidates could enhance chemical and metabolic stability, ...improve lipophilicity and bioavailability, and increase the protein bind affinity. Consequently, extensive attention has been devoted toward the development of efficient and versatile methods for introducing the CF3 group into various organic molecules. Direct trifluoromethylation reaction has become one of the most efficient and important approaches for constructing carbon–CF3 bonds. Traditionally, the nucleophilic trifluoromethylation reaction involves an electrophile and the CF3 anion, while the electrophilic trifluoromethylation reaction involves a nucleophile and the CF3 cation. In 2010, we proposed the concept of oxidative trifluoromethylation: the reaction of nucleophilic substrates and nucleophilic trifluoromethylation reagents in the presence of oxidants. In this Account, we describe our recent studies of oxidative trifluoromethylation reactions of various nucleophiles with CF3SiMe3 in the presence of oxidants. We have focused most of our efforts on constructing carbon–CF3 bonds via direct trifluoromethylation of various C–H bonds. We have demonstrated copper-mediated or -catalyzed or metal-free oxidative C–H trifluoromethylation of terminal alkynes, tertiary amines, arenes and heteroarenes, and terminal alkenes. Besides various C–H bonds, aryl boronic acids proved to be viable nucleophilic coupling partners for copper-mediated or -catalyzed cross-coupling reactions with CF3SiMe3. To further expand the reaction scope, we also applied H-phosphonates to the oxidative trifluoromethylation system to construct P–CF3 bonds. Most recently, we developed silver-catalyzed hydrotrifluoromethylation of unactivated olefins. These studies explore boronic acids, C–H bonds, and P–H bonds as novel nucleophiles in transition-metal-mediated or -catalyzed cross-coupling reactions with CF3SiMe3, opening new viewpoints for future trifluoromethylation reactions. Furthermore, we also achieved the oxidative trifluoromethylthiolation reactions of aryl boronic acids and terminal alkynes to construct carbon–SCF3 bonds by using CF3SiMe3 and elemental sulfur as the nucleophilic trifluoromethylthiolating reagent. These oxidative trifluoromethylation and trifluoromethylthiolation reactions tolerate a wide range of functional groups, affording a diverse array of CF3- and CF3S-containing compounds with high efficiencies, and provide elegant and complementary alternatives to classical trifluoromethylation and trifluoromethylthiolation reactions. Because of the importance of the CF3 and SCF3 moieties in pharmaceuticals and agrochemicals, these reactions would have potential applications in the life science fields.
A silver‐mediated oxidative difluoromethylation of styrenes and vinyl trifluoroborates with TMSCF2H is reported for the first time. This method enables direct and facile access to CF2H‐alkenes from ...abundant alkenes with excellent functional‐group compatibility. Moreover, this Ag/TMSCF2H protocol could further enable a series of radical difluoromethylation reactions of a wide array of substrates, offering a generic and complementary platform for the construction of diversified C−CF2H bonds.
A silver‐mediated oxidative difluoromethylation of styrenes and vinyltrifluoroborates with TMSCF2H to construct vinyl−CF2H bonds has been achieved for the first time. This protocol also provides a generic platform for radical difluoromethylation of a broad array of substrates including diverse alkenes, carboxylic acids, heteroarenes, and isonitriles, enabling expedient construction of diversified C−CF2H bonds.
It is highly desirable, although very challenging, to develop self‐healable materials exhibiting both high efficiency in self‐healing and excellent mechanical properties at ambient conditions. ...Herein, a novel Cu(II)–dimethylglyoxime–urethane‐complex‐based polyurethane elastomer (Cu–DOU–CPU) with synergetic triple dynamic bonds is developed. Cu–DOU–CPU demonstrates the highest reported mechanical performance for self‐healing elastomers at room temperature, with a tensile strength and toughness up to 14.8 MPa and 87.0 MJ m−3, respectively. Meanwhile, the Cu–DOU–CPU spontaneously self‐heals at room temperature with an instant recovered tensile strength of 1.84 MPa and a continuously increased strength up to 13.8 MPa, surpassing the original strength of all other counterparts. Density functional theory calculations reveal that the coordination of Cu(II) plays a critical role in accelerating the reversible dissociation of dimethylglyoxime–urethane, which is important to the excellent performance of the self‐healing elastomer. Application of this technology is demonstrated by a self‐healable and stretchable circuit constructed from Cu–DOU–CPU.
A dimethylglyoxime–urethane (DOU)‐based polyurethane elastomer self‐heals immediately at room temperature and shows world‐record strength and toughness. Cu(II)DOU coordination bonds greatly strengthen the materials while enhancing the dynamics of the DOU bonds to facilitate self‐healing. This material design reconciles the contradictory properties of mechanical robustness and self‐healing efficiency, providing a powerful new strategy to create high‐performance self‐healing materials.
A large number of reagents have been developed for the synthesis of trifluoromethylated compounds. However, an ongoing challenge in trifluoromethylation reaction is the use of less expensive and ...practical trifluoromethyl sources. We report herein the unprecedented direct trifluoromethylation of (hetero)arenes using trifluoromethanesulfonic anhydride as a radical trifluoromethylation reagent by merging photoredox catalysis and pyridine activation. Furthermore, introduction of both the CF3 and OTf groups of the trifluoromethanesulfonic anhydride into internal alkynes to access tetrasubstituted trifluoromethylated alkenes was achieved. Since trifluoromethanesulfonic anhydride is a low‐cost and abundant chemical, this method provides a cost‐efficient and practical route to trifluoromethylated compounds.
The light FFFantastic: An unprecedented application of trifluoromethanesulfonic anhydride as a radical trifluoromethylation reagent was developed by merging photoredox catalysis and pyridine activation. The synthetic utility of this method is exemplified by the C−H trifluoromethylation of (hetero)arenes and trifluoromethyltriflation of alkynes.
The development of catalytic carboacylation of simple olefins, which would enable the rapid construction of ketones with high levels of complexity and diversity, is very challenging. To date, the ...vast majority of alkene carboacylation reactions are typically restricted to single- and two-component methodologies. Here we describe a three-component carboacylation of alkenes via the merger of radical chemistry with nickel catalysis. This reaction manifold utilizes a radical relay strategy involving radical addition to an alkene followed by alkyl radical capture by an acyl-nickel complex to forge two vicinal C-C bonds under mild conditions. Excellent chemoselectivity and regioselectivity have been achieved by utilizing a pendant weakly chelating group. This versatile protocol allows for facile access to a wide range of important β-fluoroalkyl ketones from simple starting materials.
A metallaphotoredox‐catalyzed strategy for the selective and divergent aminocarbonylation of alkynes with amines and 1 atm of CO is reported. This synergistic protocol not only enables the ...Markovnikov‐selective hydroaminocarbonylation of alkynes to afford α,β‐unsaturated amides, but also facilitates a sequential four‐component hydroaminocarbonylation/radical alkylation in the presence of tertiary and secondary alkyl boronate esters, which allows for straightforward conversion of alkynes into corresponding amides. Preliminary mechanistic studies disclose that a photoinduced oxidative insertion of aniline and CO into nickel followed by a migratory insertion of (carbamoyl)nickel species could be involved.
A metallaphotoredox‐catalyzed strategy for the Markovnikov‐selective hydroaminocarbonylation of alkynes with amines and 1 atm of CO is reported, offering a novel and complementary platform for accessing α,β‐unsaturated amides. This synergistic protocol facilitates an unprecedented sequential hydroaminocarbonylation/radical alkylation process with tertiary and secondary alkyl boronate esters.
A silver bullet: The title reaction results in selective formation of trifluoromethylated alkanes, and is in contrast to the previously reported transition‐metal‐catalyzed trifluoromethylation of ...olefins to generate a series of trifluoromethylated allylic compounds. Preliminary mechanistic investigations indicate that the current hydrotrifluoromethylation proceeds through a pathway involving a CF3 radical species.
This article describes the copper-catalyzed oxidative trifluoromethylation of heteroarenes and highly electron-deficient arenes with CF3SiMe3 through direct C–H activation. In the presence of ...catalyst Cu(OAc)2, ligand 1,10-phenanthroline and cobases tert-BuONa/NaOAc, oxidative trifluoromethylation of 1,3,4-oxadiazoles with CF3SiMe3 proceeded smoothly using either air or di-tert-butyl peroxide as an oxidant to give the corresponding trifluoromethylated 1,3,4-oxadiazoles in high yields. Di-tert-butyl peroxide was chosen as the suitable oxidant for oxidative trifluoromethylation of 1,3-azoles and perfluoroarenes. Cu(OH)2 and Ag2CO3 were the best catalyst and oxidant for direct oxidative trifluoromethyaltion of indoles. The optimum reaction conditions enable oxidative trifluoromethylation of a range of heteroarenes that bear numerous functional groups. The prepared trifluoromethylated heteroarenes are of importance in the areas of pharmaceuticals and agrochemicals. The preliminary mechanistic studies of these oxidative trifluoromethylations are also reported.
We report herein the three‐component radical addition reaction of SF5Cl, alkene and diazo compounds for the selective formation of α‐alkyl‐α‐SF5 carbonyl compounds. The three‐component addition ...reaction proceeded through the first reaction of SF5 radical with the diazo compound followed by the addition of the in situ generated carbon radical to alkene. The synthetic useful α‐allyl‐α‐SF5 carbonyl compounds were successfully prepared when allyl trimethylsilanes were used as the alkene substrates. Furthermore, the three‐component adducts formed from SF5Cl, α‐diazoacetophenones and vinyl acetates were converted into pentafluorosulfanylfurans. This transformation provided a practical and efficeint method for the synthesis of pentafluorosulfanylfurans.
A three‐component radical reaction of SF5Cl, alkenes, and diazo compounds for synthesis of α‐alkyl‐α‐SF5 carbonyl compounds was developed. Furthermore, the three‐component adducts formed from SF5Cl, α‐diazoacetophenones and vinyl acetates were converted into pentafluorosulfanylfurans.
An ongoing challenge in trifluoromethylthiolation reactions is the use of less expensive and easily available trifluoromethylthio sources. Herein, we disclose an unprecedented usage of ...trifluoromethanesulfonic anhydride (Tf2O) as a radical trifluoromethylthiolating reagent. Hydrotrifluoromethylthiolation of unactivated alkenes and alkynes with Tf2O in the presence of PMePh2 and H2O under visible‐light photoredox catalysis gave the addition products. The trifluoromethylthio radical (.SCF3) was first formed from Tf2O through a photoredox radical processes and deoxygenative reduction of PMePh2, and H2O serves as the H‐atom donor for the hydrotrifluoromethylthiolation reaction. This reaction provides a new strategy for radical trifluoromethylthiolation.
A practical anti‐Markovnikov hydrotrifluoromethylthiolation of unactivated alkenes using (CF3SO2)2O and H2O as the SCF3 and H sources was achieved through deoxygenative reduction with PMePh2 and photoredox radical processes. This reaction is the first example of using (CF3SO2)2O as a trifluoromethylthiolating reagent and provides a new strategy for radical trifluoromethylthiolation.
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