Tf2 O-Catalyzed Tandem Cyclization/Trifluoromethylselenolation of Alkynes for Synthesis of CF3 Se-Containing Heterocycles.

Herein, the tandem synthesis of various CF3 Se-containing heterocyclic compounds has been developed, using Tf2 O as the catalyst and trifluoromethyl selenoxides as the electrophilic trifluoromethylselenolation reagents. This process is characterized by its mild conditions, ease of operation, and good functional group compatibility. A variety of alkynes could be transferred into CF3 Se-containing indoles, benzofurans, benzothiophenes, isoquinolines and chromenes in good yields. A key step involving the formation of the electrophilic CF3 Se species was proposed.

Vinylic Trifluoromethylselenolation via Pd-Catalyzed C-H Activation.

Trifluorometylselenolation via C-H activation is barely described in literature. In particular, no such vinylic functionalization has been yet described. Herein, a palladium-catalyzed trifluoromethylselenolation of vinylic C-H bonds is described. The 5-methoxy-8-aminoquinoline has been used as auxiliary directing group to perform this reaction. The reaction gives excellent yields with α-substituted compounds whatever the substituents and a microwave activation can be used to accelerate the reaction. With ß-substituted substrates lower yields, but still satisfactory, are obtained. This methodology was also successfully extended to other fluoroalkylselenyl groups.

Gold (I/III)-Catalyzed Trifluoromethylthiolation and Trifluoromethylselenolation of Organohalides.

The first C-SCF3 /SeCF3 cross-coupling reactions using gold redox catalysis [(MeDalphos)AuCl], AgSCF3 or Me4 NSeCF3 , and organohalides as substrates are reported. The new methodology enables a one-stop shop synthesis of aryl/alkenyl/alkynyl trifluoromethylthio- and selenoethers with a broad substrate scope (>60 examples with up to 97 % isolated yield). The method is scalable, and its robustness is evidenced by the late-stage functionalization of various bioactive molecules, which makes this reaction an attractive alternative in the synthesis of trifluoromethylthio- and selenoethers for pharmaceutical and agrochemical research and development.

Aromatic Trifluoromethylselenolation via Pd-catalyzed C-H functionalization.

The synthesis of trifluoromethylselenolated aromatic molecules via an auxiliary-assisted, palladium catalyzed, C-H bonds functionalization with trifluoromethyl tolueneselenosulfonate as reagent is described. The mono- or bis-products can be preferentially formed. Some mechanistic investigations were realized to better understand the reaction. This methodology was also extended to fluoroalkylselenyl groups.

Forging C-SeCF3 Bonds with Trifluoromethyl Tolueneselenosulfonate under Visible-Light.

This account highlights some of our recent work on photoinduced trifluoromethylselenolation reactions. This research program relies primarily on the design of a new key shelf-stable selenating reagent that can be involved in various radical processes In particular, we demonstrated that trifluoromethylselenolation of arenes, alkenes, alkynes as well as aliphatic organic building blocks can be readily achieved under visible-light irradiation. Mechanistic investigations based on 19 F NMR studies, EPR spectroscopy, cyclic voltammetry and luminescence studies allowed us to shed the light on the different proposed mechanisms in the designed methodologies. The applicative potential of these strategies was further demonstrated through the synthesis of bioactive analogue containing SeCF3 motif.

Metal-free nucleophilic trifluoromethylselenolation via an iodide-mediated umpolung reactivity of trifluoromethylselenotoluenesulfonate.

We report herein a practical method to generate CF3Se- (and RFSe-) anions from shelf-stable reagents under iodide activation. Metal-free nucleophilic trifluoromethylselenolations have been then performed with this in situ-generated anion. Perfluoroalkylselenolations have also been described.

Copper-promoted/copper-catalyzed trifluoromethylselenolation reactions.

Copper catalysis and, more generally, copper chemistry are pivotal for modern organofluorine chemistry. Major advances have been made in the field of trifluoromethylselenolations of organic compounds where copper catalysis played a crucial role. Recent developments in this field are highlighted in this minireview.

Metal-Free Alpha Trifluoromethylselenolation of Carbonyl Derivatives under Batch and Flow Conditions.

Trifluoromethylselenolated carbonyl compounds represent an emerging class with potential applications in several fields; however, a widespread use of such compound is hampered by the very limited number of strategies for their preparation. In this study we developed a method for the preparation of α-SeCF3 substituted carbonyl derivatives using an in situ generated electrophilic ClSeCF3 species. We also implemented an in-flow protocol to improve the safety features of the process.

Visible-Light-Mediated Metal-Free Synthesis of Trifluoromethylselenolated Arenes.

The first visible-light-mediated synthesis of trifluoromethylselenolated arenes under metal-free conditions is reported. The use of an organic photocatalyst enables the trifluoromethylselenolation of arene diazonium salts using the shelf-stable reagent trifluoromethyl tolueneselenosulfonate at room temperature. The reaction does not require the presence of any additives and shows high functional-group tolerance, covering a very broad range of starting materials. Mechanistic investigations, including EPR spectroscopy, luminescence investigations, and cyclic voltammetry allow rationalization of the reaction mechanism.

Trifluoromethyl- and Fluoroalkylselenolations of Alkynyl Copper(I) Compounds.

The successful perfluoroalkylselenolation of alkynyl copper(I) compounds is described herein. The reaction occurs under oxidant free conditions at room temperature. This convenient one-pot procedure is based on the in situ generation of trifluoromethylselenyl chlorides. The developed system shows high functional group tolerance and also promotes the employment of fluoroalkyl derivatives.

Electrophilic Trifluoromethylselenolation of Boronic Acids.

Trifluoromethylselenylated compounds are emergent compounds with interesting physicochemical properties that still suffer from a lack of efficient synthetic methods. We recently developed an efficient one-pot strategy to generate in situ CF3SeCl and use it in various reactions. Herein, we continue our study of the reactivity scope of this preformed reagent. Cross-coupling reactions with aromatic and heteroaromatic boronic acids have been investigated. The expected products have been obtained, using a stoichiometric amount of copper, with moderate yields.

Electrophilic trifluoromethylselenolation of terminal alkynes with Se-(trifluoromethyl) 4-methylbenzenesulfonoselenoate.

Herein the nucleophilic addition of Se-(trifluoromethyl) 4-methylbenzenesulfonoselenoate, a stable and easy-to-handle reagent, to alkynes is described. This reaction provides trifluoromethylselenylated vinyl sulfones with good results and the method was extended also to higher fluorinated homologs. The obtained compounds are valuable building blocks for further syntheses of fluoroalkylselenolated molecules.

Synthesis of Cu(I) trifluoromethylselenates for trifluoromethylselenolation of aryl and alkyl halides.

The development of new strategies for synthesis of trifluoromethylthiolate compounds is of considerable importance in pharmaceuticals, agrochemicals, and advanced materials. Accordingly, currently much attention is being devoted to the development of effective methods and reagents for their synthesis. In contrast, considerably less effort has been afforded to the development of preparing CSeCF3 bonds. Herein we report a concise route to synthesize a family of copper(I) trifluoromethylselenolate reagents by the reaction of CuI with the Ruppert's reagent (Me3 SiCF3 ), KF, and elemental selenium in the presence of dinitrogen ligands in CH3 CN at room temperature. The reagent [Cu(bpy)(SeCF3 )]2 was proven to be air-stable and highly efficient for nucleophilic trifluoromethylthselenolation of a broad range of (hetero)aryl halides and alkyl halides. This method represents a powerful protocol for the construction trifluoromethylselenolate compounds.

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.