Bilguun Bayarmagnai

Sandmeyer Trifluoromethylation of Arenediazonium Tetrafluoroborates

The development of methods for the introduction of trifluoromethyl groups into functionalized molecules is of great importance due to their presence in many top-selling pharmaceuticals, agrochemicals, and functional materials. Trifluoromethyl groups are known to impart desirable properties, such as higher metabolic stability, increased lipophilicity, and stronger dipole moments to druglike molecules. Celecoxib, dutasteride, fluoxetine, and sitagliptin are some examples of top-selling pharmaceuticals featuring trifluoromethyl groups, and beflubutamid, diflufenican, and norfluazon examples of agrochemicals. However, traditional methods to access benzotrifluorides, for example, the Swarts reaction, typically require harsh conditions and have a low substrate scope, so that they are confined to the beginning of a synthetic sequence (Scheme 1a). Building on pioneering work on Cu– and Pd–perfluoroalkyl complexes by McLoughlin, Yagupolskii, Burton, Chambers, Grushin, and others, substantial progress has recently been made in the development of trifluoromethylation reactions that allow the selective introduction of CF3 groups into functionalized, late-stage synthetic intermediates. A wealth of new reactions has been disclosed, which can be roughly divided into five categories (Scheme 1b–f). The first are couplings of aryl halides with nucleophilic CF3 reagents (reaction type b), usually copper–CF3 complexes in stoichiometric amounts. These complexes may also be generated in situ from copper salts and Ruppert s reagent (CF3SiMe3), [7] fluoroform, potassium (trifluoromethyl)trimethoxyborate, trifluoroacetate salts, methyl trifluoroacetate, or fluorosulfonyldifluoroacetic acid. Grushin, Sanford, and Buchwald also disclosed trifluoromethylations of aryl halides based on palladium complexes. Palladium complexes also promote C H functionalizations of arenes with trifluoromethylating reagents (reaction type c). Examples are the ortho-trifluoromethylation of donor-substituted arenes with Umemoto s reagent described by Yu et al. and the Pd-catalyzed coupling of arenes with perfluoroalkyl iodides reported by Sanford et al. C H trifluoromethylations of heteroarenes have recently been reported also with nucleophilic trifluoromethylation reagents under oxidative conditions. Examples of couplings of aryl nucleophiles with electrophilic CF3 sources (reaction type d) include the coupling of arylboronic acids with Togni s and Umemoto s reagent disclosed by Shen and Liu, respectively. Sanford et al. employed a copper/ruthenium photocatalyst system to promote a radical trifluoromethylation of boronic acids. The copper-catalyzed syntheses of benzotrifluorides from boronic acids and CF3SiMe3 or K [CF3B(OMe)3] developed by Qing et al. and ourselves exemplify oxidative couplings of aryl nucleophiles with nucleophilic CF3 reagents (reaction type e). The radical trifluoromethylation of arenes (reaction type f) was pioneered by Langlois. Baran and MacMillan recently reported modern variants of this reaction concept based on peroxide or ruthenium initiators. From a practical standpoint, nucleophilic reagents are appealing for the introduction of trifluoromethyl groups for the following reasons. CF3SiMe3 and K [CF3B(OMe)3] are available in large quantities for a reasonable price, and are easy to store and handle. They are accessible not only from halofluorocarbons, but also from fluoroform, a by-product in the production of Teflon. One of the most widely used methods for the introduction of halides and related nucleophiles is the Sandmeyer reaction. Aromatic amines, which are available in great structural diversity, are diazotized using, for example, NaNO2 or organic nitrites. Upon treatment with the appropriate copper(I) halides, nitrogen gas is released, and a halide group is installed regiospecifically in the position Scheme 1. Strategies for the introduction of trifluoromethyl groups.

Sandmeyer trifluoromethylthiolation of arenediazonium salts with sodium thiocyanate and Ruppert–Prakash reagent

In the presence of copper thiocyanate, sodium thiocyanate and the inexpensive, easy-to-use trifluoromethylating reagent Me3Si–CF3, diazonium salts are smoothly converted into the corresponding aryl trifluoromethyl thioethers. Combined with diazotisation, this convenient and inexpensive method allows the straightforward synthesis of aryl or heteroaryl trifluoromethyl thioethers from the corresponding anilines.

Iron‐Catalyzed Decarboxylation of Trifluoroacetate and Its Application to the Synthesis of Trifluoromethyl Thioethers

Nucleophilic CF3 has been generated by decarboxylation of potassium trifluoroacetate, arguably the most easy-to-handle, inexpensive, and sustainable source of trifluoromethyl groups. Simple iron(II) chloride catalyzes the decarboxylation as well as a subsequent trifluoromethylation of organothiocyanates, resulting in a straightforward synthesis of trifluoromethyl thioethers. The KCN byproduct is absorbed by iron(II) with formation of nontoxic potassium hexacyanoferrate. An analogous trifluoromethylation of aldehydes with trifluoroacetate underlines the synthetic potential of such iron-catalyzed decarboxylative trifluoromethylations.

Convenient synthesis of pentafluoroethyl thioethers via catalytic Sandmeyer reaction with a stable fluoroalkylthiolation reagent

Aromatic and heteroaromatic diazonium salts were smoothly converted into the corresponding pentafluoroethyl thioethers by reaction with Me4NSC2F5 in the presence of catalytic amounts of elemental copper. This Sandmeyer-type reaction proceeds at room temperature under mild conditions and is applicable to a wide range of functionalised molecules. It enables the late-stage introduction of pentafluoroethylthio groups, a promising but largely unexplored substituent, into bioactive molecules.

Structurally stressed PT09SBA: A close look at the properties of large pore photoluminescent, redox active mesoporous hybrid silica

A thien-2-yl substituted, electron-rich phenothiazine has been converted over several steps into a redox active sol–gel precursor. Following a fluoride-catalyzed synthesis, a phenothiazine-based mesoporous hybrid organosilica was obtained. The electrochemical behavior and the luminescence properties of the immobilized chromophore have been studied using solid state fluorescence spectroscopy, electron paramagnetic resonance spectroscopy (EPR) and solid state voltammetry (CV and DPV). The influence of both the presence of fluoride anions and the acidic pH during the material synthesis were explored by means of scanning and transmission electron microscopy (SEM and TEM), X-ray powder diffraction (XRD) and nitrogen physisorption measurements. While a combination of acidic pH and fluoride was found necessary for the material formation, partial cleavage of the precursor was observed. Data obtained from both the chemical as well as the electrochemical oxidation/reduction of the immobilized PT dye indicates the formation of an organic layer containing several species inside the pore channels.