Photoinduced Trifluoromethylselenolation of Aryl Halides with [Me4N][SeCF3].

A visible-light-induced metal-free trifluoromethylselenolation of aryl iodides and bromides with [Me4N][SeCF3] is described. The reaction was conducted at ambient temperature by successfully harnessing the light-sensitive SeCF3 reagent. Mechanistically, the EDA complexes between aryl halide and the -SeCF3 anion or the base might be formed and excited by light, which subsequently undergo intracomplex SET processes to generate aryl and •SeCF3 radicals as key intermediates, allowing a convenient and green access to various aryl trifluoromethyl selenoethers.

Photoinduced Copper-Promoted Decarboxylative Trifluoromethylselenolation of Aromatic Carboxylic Acids with [Me4N][SeCF3].

Visible-light-induced decarboxylative trifluoromethylselenolation of (hetero)aromatic carboxylic acids with [Me4N][SeCF3], oxidant, and catalysts afforded a variety of (hetero)aryl trifluoromethyl selenoethers in good yields. The reaction might involve a radical process, which generated (hetero)aryl radicals from the stable (hetero)aromatic carboxylic acids via oxidative decarboxylation with NFSI as the oxidant, [di-tBu-Mes-Acr-Ph][BF4] as the photocatalyst, and 1,1'-biphenyl as the cocatalyst. Both catalysts had a decisive influence on the reaction. The trifluoromethylselenolation was further promoted by the copper salts probably via Cu-mediated cross-coupling of the sensitive SeCF3 species with the in situ formed (hetero)aryl radicals. Advantages of the method include visible light irradiation, mild reaction conditions at ambient temperature, good functional group tolerance, no pre-functionalization/activation of the starting carboxylic acids, and applicability to drug molecules. This protocol is promising and synthetically useful, which overcame the limitations of the known trifluoromethylselenolation methods and represented the first decarboxylative trifluoromethylselenolation of (hetero)aromatic carboxylic acids.

Recent Advances in the Synthesis and Transformation of Carbamoyl Fluorides, Fluoroformates, and Their Analogues.

Carbamoyl fluorides, fluoroformates, and their analogues are a class of important compounds and have been evidenced as versatile building blocks for the preparation of useful molecules in organic chemistry. While major achievements were made in the synthesis of carbamoyl fluorides, fluoroformates, and their analogues in the last half of 20th century, an increasing number of reports have focused on using O/S/Se=CF2 species or their equivalents as the fluorocarbonylation reagents for the direct construction of these compounds from the parent heteroatom-nucleophiles in recent years. This review mainly summarizes the advances in the synthesis and typical application of carbamoyl fluorides, fluoroformates, and their analogues by the halide exchanges and fluorocarbonylation reactions since 1980.

Divergent dehydroxyfluorination and carbonation of alcohols with trifluoromethyl trifluoromethanesulfonate.

Preparation of alkyl fluorides and carbonates via divergent dehydroxyfluorination and carbonation of alcohols with trifluoromethyl trifluoromethanesulfonate (CF3SO2OCF3) is described. The reactions performed with BTMG in THF provided alkyl fluorides in good yields, whereas those of two different alcohols with Et3N in DCM formed asymmetric carbonates in moderate to excellent yields. CF3SO2OCF3 was demonstrated to be either a "F" or a "CO" reagent in the reactions by changing the base, allowing the selective construction of alkyl fluorides and carbonates from the corresponding alcohols with high efficiency. Notably, the fluorine-containing asymmetric carbonates that are difficult to synthesize by other methods were comprehensively prepared by this method, which would have great application potential in both academic and industrial fields.

Copper-mediated aerobic trifluoromethyltelluration of boronic acids with [Me4N][TeCF3].

A copper-mediated trifluoromethyltelluration of arylboronic acids with [Me4N][TeCF3] using air as an environmental friendly oxidant is presented. The reaction proceeded smoothly under mild conditions in the presence of Cu(OTf)2 and bipyridine to provide the corresponding trifluoromethyltellurated products in good yields. Vinylboronic acid and arylboronic acid pinacol ester were also suitable substrates in the conversion but the yields are low. This transformation featured simplicity, good functional group tolerance, and a wide range of substrates, allowing for a convenient access to various TeCF3-containing molecules, and represented the first Chan-Lam type trifluoromethyltelluration with the highly reactive [Me4N][TeCF3] salt.

Deuteration of Arylthianthren-5-ium Salts in CD3OD.

Deuteration of arylthianthren-5-ium triflates with CD3OD or CD3OD/CD3COCD3 in the presence of Cs2CO3 by palladium catalysis or photoirradiation allowed the convenient synthesis of deuterated arenes in good yields. The Pd-catalyzed reaction generally gave better yields than the photoinduced deuteration, but exceptions also exist. They could complement each other in some cases. These reactions featured eco-friendly conditions, simplicity, inexpensive deuterium sources, good functional group tolerance, and a range of substrates. Since arylthianthren-5-ium salts could be readily synthesized from arenes and thianthrene 5-oxide, this protocol provided a formal aromatic C-H deuteration with high selectivity, enabling efficient deuterium labeling of multifunctionalized arenes and drug molecules.

Palladium-catalyzed C-H trifluoromethylselenolation of arenes with [Me4N][SeCF3] and an oxidant.

Trifluoromethylselenolation of arenes with [Me4N][SeCF3] in the presence of an oxidant through Pd-catalyzed C(sp2)-H activation under the assistance of a directing group is established for the first time. The reaction tolerates different directing groups and a variety of functional groups, enabling selective installation of a SeCF3 moiety onto the ortho positions of arenes. Mechanistic studies revealed that the CF3SeSeCF3 intermediate in situ generated from oxidation of [Me4N][SeCF3] might be the real SeCF3 reagent in the reaction.

Revisiting the Balz-Schiemann Reaction of Aryldiazonium Tetrafluoroborate in Different Solvents under Catalyst- and Additive-Free Conditions.

The thermal and photochemical Balz-Schiemann reaction in commonly used solvents was revisited under catalyst- and additive-free conditions. The study showed that using low- or non-polar solvents could improve the pyrolysis and photolysis of aryldiazonium tetrafluoroborates, enabling effective fluorination at a low temperature or under visible-light irradiation. PhCl and hexane were exemplified as cheap and reliable solvents for both reactions, providing good to excellent yields of aryl fluorides from the corresponding diazonium tetrafluoroborates. The combination of slight heating with visible-light irradiation was beneficial for the transformation of stable aryldiazonium tetrafluoroborates. Nevertheless, the electronic and steric nature of aryldiazonium tetrafluoroborates still had a pivotal effect on both fluorinations even in these solvents.

Pd/Cu-Catalyzed Vinylation of Terminal Alkynes with (2-Bromoethyl)diphenylsulfonium Triflate.

The potential of (2-bromoethyl)diphenylsulfonium triflate to be a powerful vinylation reagent was determined by the Sonogashira cross-coupling reactions with terminal alkynes. The vinylation proceeded smoothly at 25 °C under Pd/Cu catalysis to afford a variety of 1- and 2-unsubstituted 1,3-enynes in moderate to excellent yields. This protocol represents the first application of (2-haloethyl)diphenylsulfonium triflate as a CH═CH2 transfer source in organic synthesis.

Synthesis and Biological Evaluation of CF3 Se-Substituted α-Amino Acid Derivatives.

Several CF3 Se-substituted α-amino acid derivatives, such as (R)-2-amino-3-((trifluoromethyl)selanyl)propanoates (5 a/6 a), (S)-2-amino-4-((trifluoromethyl)selanyl)butanoates (5 b/6 b), (2R,3R)-2-amino-3-((trifluoromethyl)selanyl)butanoates (5 c/6 c), (R)-2-((S)-2-amino-3-phenylpropanamido)-3-((trifluoromethyl)selanyl)propanoates (11 a/12 a), and (R)-2-(2-aminoacetamido)-3-((trifluoromethyl)selanyl)propanoates (11 b/12 b), were readily synthesized from natural amino acids and [Me4 N][SeCF3 ]. The primary in vitro cytotoxicity assays revealed that compounds 6 a, 11 a and 12 a were more effective cell growth inhibitors than the other tested CF3 Se-substituted derivatives towards MCF-7, HCT116, and SK-OV-3 cells, with their IC50 values being less than 10 µM for MCF-7 and HCT116 cells. This study indicated the potentials of CF3 Se moiety as a pharmaceutically relevant group in the design and synthesis of novel biologically active molecules.

Trifluoromethylselenolation and N-acylation of indoles with [Me4N][SeCF3].

An efficient method for oxidative trifluoromethylselenolation/N-acylation of indoles with excess [Me4N][SeCF3] in the presence of acyl peroxides and their derivatives is described. The reaction is easy to handle, proceeds smoothly at room temperature under metal-free conditions, and shows advantages such as good functional group tolerance, excellent regioselectivity, and compatibility of a number of substrates, producing 1-acyl and 3-trifluoromethylselanyl substituted indoles in good yields. Acyl peroxides and peroxycarboxylic acid behave as both oxidants and acyl sources in the transformation. This one-pot procedure provides a convenient access to a new class of indole derivatives, representing the first trifluoromethylselanyl bifunctionalization of indoles with the nucleophilic [Me4N][SeCF3] reagent.

Pd/Cu-Catalyzed C-H/C-H Cross Coupling of (Hetero)Arenes with Azoles through Arylsulfonium Intermediates.

A highly efficient method for the selective formal C-H/C-H cross-coupling of azoles and (hetero)arenes was established through arylsulfonium intermediates under transition-metal catalysis, which produced a variety of 2-(hetero)aryl azoles in good to excellent yields. Advantages of the reaction included mildness, a good functional group tolerance, a wide range of substrates, a high regio- and chemoselectivity, one-pot procedures, and the late-stage functionalization of complex molecules without the use of oxidants, offering a promising strategy for the transition-metal-catalyzed C-H arylation of azoles.

Markovnikov-Type Hydrotrifluoromethylchalcogenation of Unactivated Terminal Alkenes with [Me4N][XCF3] (X = S, Se) and TfOH.

The first Markovnikov-type hydrotrifluoromethylselenolation of unactivated terminal alkenes with the readily accessible [Me4N][SeCF3] reagent and the superacid TfOH is reported. The reaction proceeded at room temperature under catalyst- and additive-free conditions to give the branched trifluoromethylselenolated products in good yields. This protocol is also applicable to the Markovnikov-type hydrotrifluoromethylthiolation of unactivated terminal alkenes using [Me4N][SCF3]/TfOH, but not to the hydrotrifluoromethoxylation with CsOCF3/TfOH under the same conditions. The successful hydrotrifluoromethylselenolation and hydrotrifluoromethylthiolation showed simplicity and high regioselectivity, taming the sensitive -XCF3 (X = Se, S) anions with TfOH, and offered a convenient method for the straightforward synthesis of branched trifluoromethyl selenoethers and thioethers from unactivated alkenes.

Tertiary-Amine-Initiated Synthesis of Acyl Fluorides from Carboxylic Acids and CF3 SO2 OCF3.

A convenient method for deoxyfluorination of aromatic and aliphatic carboxylic acids with CF3 SO2 OCF3 in the presence of a suitable base at room temperature has been developed. The reaction allows a straightforward access to a variety of acyl fluorides and proves that CF3 SO2 OCF3 is an effective deoxyfluorination reagent for carboxylic acids. The method features simplicity, expeditiousness, high efficiency, ease of handling, good functional group tolerance, a wide range of substrates, excellent yields of products, compatibility of many amine initiators, use of environmentally friendly reagents, and effortless removal of byproducts. This reaction represents the first utilization of trifluoromethyl trifluoromethanesulfonate as a fluorination reagent.

CaCl2-Promoted Dehydroxytrifluoromethylselenolation of Alcohols with [Me4N][SeCF3].

A direct trifluoromethylselenolation of alcohols with the readily accessible [Me4N][SeCF3] salt has been reported. The reaction is significantly promoted by CaCl2 and proceeds smoothly through unprecedented carbonoselenoate intermediates to form the corresponding alkyl trifluoromethyl selenoethers in good yields. This protocol is also applicable to the late-stage dehydroxytrifluoromethylselenolation of complex alcohols owing to its mildness, good compatibility, high efficiency, and broad functional group tolerance.

Fluoroalkylation of Diazo Compounds with Diverse Rfn Reagents.

Progress in the transition-metal-catalyzed or -free fluoroalkylation of diazo compounds with different types of fluoroalkyl (Rfn ) transfer reagents is summarized in this review. Special attention is focused on the straightforward trifluoromethylation, gem-difluoroolefination, trifluoromethoxylation, fluoroalkylthiolation, and trifluoromethylselenolation of diazo substrates. The mechanistic insights and the application of some of the products are also discussed in this article. We believe that this review will inspire both young and experienced chemists to further study the direct fluoroalkylation of diazo compounds as an efficient and convenient way to build complex fluorine-containing molecules.

Oxidative trifluoromethylselenolation of 1,3-dicarbonyls with [Me4N][SeCF3].

Reactions of 1,3-ketoesters, -diesters, -diketones, and -ketoamides with [Me4N][SeCF3] in the presence of an appropriate oxidant provided a series of 2-trifluoromethylselenolated 1,3-dicarbonyls in moderate to good yields. The trifluoromethylselenolation featured simplicity, mildness, high efficiency, transition-metal-free conditions, and compatibility of various oxidants, and represented the first oxidative trifluoromethylselenolation of 1,3-dicarbonyl compounds with [Me4N][SeCF3]. This protocol was also applicable to the oxidative trifluoromethylthiolation of 1,3-dicarbonyls with [Me4N][SCF3]/NCS, and oxidative trifluoromethylchalcogenation with nucleophilic XCF3 (X = O, S, and Se) reagents were compared. The results demonstrated that these nucleophilic XCF3 salts showed different reaction profiles towards 1,3-dicarbonyls under oxidation conditions.

Fluorine-Containing Inhalation Anesthetics: Chemistry, Properties and Pharmacology.

Studies on fluorinated inhalation anesthetics, including synthesis, physical chemistry and pharmacology, have been summarized in this review. Retrospecting the history of inhalation anesthetics revealed their increasing reliance on fluorine and ether structures. Halothane causes a rare but severe immune-based hepatotoxicity, which was replaced by enflurane in the 1970s. Isoflurane replaced enflurane in the 1980s, showing modest advantages (e.g. lower solubility, better metabolic stability, and without convulsive predisposition). Desflurane and sevoflurane came into use in the 1990s, which are better anesthetics than isoflurane (less hepatotoxicity, lower solubility, and/or markedly decreased pungency). However, they are still less than perfect. To gain more ideal inhalation anesthetics, a large number of fluorinated halocarbons, polyfluorocycloalkanes, polyfluorocycloalkenes, fluoroarenes, and polyfluorooxetanes, were prepared and their potency and toxicity were evaluated. Although the pharmacology studies suggested that some of these agents produced anesthesia, no further studies were continued on these compounds because they showed obvious lacking as anesthetics. Moreover, the anesthetic activity cannot be simply predicted from the molecular structures but has to be inferred from the experiments. Several regularities were found by experimental studies: 1) the potency and toxicity of the saturated linear chain halogenated ether are enhanced when its molecular weight is increased; 2) the margin of safety decreases and the recovery time is prolonged when the boiling point of the candidate increases; and 3) compounds with an asymmetric carbon terminal exhibit good anesthesia. Nevertheless, the development of new inhalation anesthetics, better than desflurane and sevoflurane, is still challenging not only because of the poor structure/activity relationship known so far but also due to synthetic issues.

Organic Photoredox-Catalyzed Decarboxylative Trifluoromethylselenolation of Aliphatic Carboxylic Acids with [Me4N][SeCF3].

Oxidative decarboxylation/trifluoromethylselenolation of primary, secondary, and tertiary aliphatic carboxylic acids with the nucleophilic [Me4N][SeCF3] salt and an organic photocatalyst is described. The reaction proceeds smoothly at room temperature under transition-metal-free conditions and affords the corresponding trifluoromethylselenolated products in good yields. Advantages of the method include good functional group tolerance, without preactivation of the acids, and late-stage functionalization of the complex drug molecules. This protocol represents the first decarboxylative trifluoromethylselenolation of carboxylic acids to trifluoromethyl selenoethers.

Ullmann-type N-arylation of anilines with alkyl(aryl)sulfonium salts.

A palladium/copper-cocatalyzed Ullmann-type N-arylation of anilines using alkyl(aryl)sulfonium triflates as arylation reagents has been accomplished. The reaction enabled Caryl-S bond cleavage over Calkyl-S bond breakage of alkyl(aryl)sulfoniums by Pd(P(tBu)3)2/CuI and gave the corresponding N-arylated products in good to high yields. It was also significant that the reactions of aniline with asymmetric butyl(mesityl)(aryl)sulfonium triflates showed excellent selectivity, in which the aryl groups other than the bulky and electron-rich mesityl moieties were transformed.