Synthesis of Fluorinated and Fluoroalkylated Heterocycles Containing at Least One Sulfur Atom via Cycloaddition Reactions

Fluorinated heterocycles constitute an important group of organic compounds with a rap- idly growing number of applications in such areas as medicinal chemistry, agrochemicals produc- tion, polymer chemistry, as well as chemistry of advanced materials. In the latter case, fluorinated thiophenes are considered as a lead class of compounds with numerous spectacular applications. On the other hand, cycloaddition reactions offer a superior methodology for stereo-chemically con- trolled synthesis of heterocycles with a diverse ring size and a variable number of heteroatoms. A comprehensive review of methods based on cycloaddition reactions and applied for construction of fluorinated and/or fluoroalkylated S-heterocycles has not yet been published. For this reason, the main goal of the presented review was to fill the existing gap and to summarize the results pub- lished over last six decades. In this context, the [3+2]- and [4+2]-cycloadditions (Huisgen reactions, and Diels–Alder reactions, respectively) are of special importance. Some questions related to the discussed mechanisms of cycloaddition processes observed in reactions with electron deficient, fluorinated substrates (dipolarophiles and dienophiles), and electron-rich sulfur containing counter partners, are of fundamental importance for the development of interpretations of organic reaction mechanisms

Fenntartható fluoros kémia = Sustainable fluorous chemistry

(1) A „zöldebb” fluoros kémia kialakítása érdekében számos trifluormetil-csoportban gazdag reagens hatékony szintézisét dolgoztuk ki, melyek könnyen hozzáférhető szerves fluorvegyületek hasznosítására és várhatóan nagyobb környezeti lebomlási készségére hívják fel a figyelmet. (2) Eljárásokat dolgoztunk ki 3-perfluoralkil-propanol és 3-perfluoralkil-propén típusú intermedierek előállítására, illetve a köztitermékként megjelenő ún. jódhidrinek sokoldalú preparatív átalakítására. (3) Új típusú fluoros ionos folyadékokat, imidazólium-sókat és más intermediereket állítottunk elő. (4) Orosz fejlesztésű kompozit anyagokat (FUKM, FUKM-M és FUKM-MT) kémiai reagensként, illetve átmenetifém katalizátor (Pd/FUKM) hordozóként alkalmaztunk. (5) Tanulmányoztuk a Hiyama- és a Heck-kapcsolási reakciók mechanizmusát és szintetikus alkalmazhatóságát. (6) CF3I reagnest S-alkilezőszerként alkalmaztuk (7) Prof. Bühlmann al együttműködve fluoros ionofórokat és elektrokémiai szenzorokat készítettünk. (8) Azonosítottuk egy új potenciális fluorátvivő reagens molekulaszerkezeti feltételeit, melynek segítségével lehetőségünk nyílik a fluoros kémiából (fluortartalmú modulok) a fluorkémiába (szén-fluor kötesek kialakítása) átlépnünk. Ez lehetőséget ad a gyógyszerkémia számára fontos egy, kettő, vagy három fluoratomot tartalmazó vegyületek hatékony előállításához. Több közlemény csak a kövtekező évben fog megjelenni, kérem az értékelésnél ezt vegyék figyelembe. | (1) For Greener Fluorous Chemistry we developed the synthesis of several reagents from easily accessible precursor, reach in CF3-goups, which expected to have less impact and shorter environmental half-lives. (2) Novel methods for the synthesis of 3-perfluoroalkyl-propanols and –propenes were disclosed along with the uses of their synthetic intermediates. (3) New types of fluorous ionic liquids were synthesised based on imidazolium-salts. (4) Carbon-fluorinated carbon composite materials of Russian origin were applied as chemical reagents and transition metal catalyst support material (e.g. Pd/FUKM) . (5) Hiyama- and Heck-reactions with fluorous substrates were studied for a synthetic and mechanistic point of view. (6) Trifluoroiodomethane was used for improved S-alkylating processes. (7) Fluorous ionophores and electrochemical sensors were designed for the first time in co-operation with Prof. Bühlmann. (8) The structural requirements for a potential new fluorine-transfer reagent were identified and a Patentable process designed. This will allow the introduction of one, two or three fluorine atoms into target pharmaceutical molecules, and allow a shift from the fluorous to the fluorine chemistry (i.e. from F-building blocks to create C-F bonds). Please consider that some more publications are expected to appear only in the next year

Stable Carbenes as Structural Components of Partially Saturated Sulfur-Containing Heterocycles

Recently, an unusual elongation of the C-S bond was observed experimentally for some sulfur-containing heterocycles. Using a superior ab initio (SCS-MP2/cc-pVTZ) level of theory, we showed that the phenomenon can be explained by a contribution of a donor-acceptor adduct of a carbene with an unsaturated ligand. One may achieve further elongation of the C-S bond, eventually turning it to a coordinate one, by increasing the stability of each part of the system as, e.g., in the utmost case of spiro adducts with Arduengo carbenes. The effect of carbene stability was quantified by employing the isodesmic reactions of carbene exchange.Peer reviewe

Stable Carbenes as Structural Components of Partially Saturated Sulfur-Containing Heterocycles

Recently, an unusual elongation of the C-S bond was observed experimentally for some sulfur-containing heterocycles. Using a superior ab initio (SCS-MP2/cc-pVTZ) level of theory, we showed that the phenomenon can be explained by a contribution of a donor–acceptor adduct of a carbene with an unsaturated ligand. One may achieve further elongation of the C-S bond, eventually turning it to a coordinate one, by increasing the stability of each part of the system as, e.g., in the utmost case of spiro adducts with Arduengo carbenes. The effect of carbene stability was quantified by employing the isodesmic reactions of carbene exchange

Stable Carbenes as Structural Components of Partially Saturated Sulfur-Containing Heterocycles

Recently, an unusual elongation of the C-S bond was observed experimentally for some sulfur-containing heterocycles. Using a superior ab initio (SCS-MP2/cc-pVTZ) level of theory, we showed that the phenomenon can be explained by a contribution of a donor–acceptor adduct of a carbene with an unsaturated ligand. One may achieve further elongation of the C-S bond, eventually turning it to a coordinate one, by increasing the stability of each part of the system as, e.g., in the utmost case of spiro adducts with Arduengo carbenes. The effect of carbene stability was quantified by employing the isodesmic reactions of carbene exchange

Oxidation and chlorination reactions of perfluoroketene-N,S-acetals

International audienc

Reactions of 2-oxo-2-polyfluoroalkyl-sulfones and –sulfamides with nucleophiles

<p>Reactions of 2-oxo-2-polyfluoroalkyl-sulfones and -sulfamides with heteronucleophiles—amines, alcohols, thiols and trialkyl phosphites—are studied. 2-Oxo-2-polyfluoroalkyl-sulfones and -sulfamides react with primary arylamines affording 2-imino-2-polyfluoroalkyl-sulfones and -sulfamides, whereas reactions with primary alkylamines and secondary amines result in the formation of alkylammonium enolate salts. Treatment of 2-oxo-2-polyfluoroalkyl-sulfones and -sulfamides with alcohols and thiols gives hemi(thio)ketals. Reactions of 2-oxo-2-trifluoromethyl-sulfones(-sulfamides) with trimethyl phosphite produce equimolar mixture of dimethyl(3-sulfonyl-1,1,1-trifluoropropan-2-yl)phosphate and 3,3,3-trifluoro-2-methoxy-1-sulfonylprop-1-ene.</p

The Antiviral Activity of Trifluoromethylthiolane Derivatives

The search for new antiviral agents is an important task today. The aim of this study was to elucidate the impact of trifluoromethylthiolane derivatives on herpetic and adenoviral infections. It was found that the 2-hydroxy-2-trifluoromethylthiolane significantly inhibited Herpes simplex virus type 1 (HSV-1) reproduction, reducing the virus titer obtained de novo. Such activity indicates that virus offspring are formed, but the virus particles are not complete and are not able to cause an infection process. Therefore, trifluoromethylthiolane derivatives may be a potential compounds for the development on their basis agents for the treatment of herpetic infections

Synthesis of new 3-(2,2,2-trifluoroethyl)-5-hydroxy-5-(phenylsulfanyl- or phenylsulfonyl-methyl)-1,5-dihydropyrrol-2-ones starting from alpha,beta-unsaturated gamma-lactones and primary amines

The paper presents an efficient and straightforward transformation of alpha,beta-unsaturated gamma-lactones into 2,2,2-trifluoroethyl substituted gamma-lactams, starting from a variety of primary amines. The structures of all new compounds were ascribed using 1D NMR (F-19, H-1, C-13), IR, MS. Selected 19F, 13 C NMR and IR data of gamma-lactams were compared to those of one which was characterized by X-ray diffraction analysis. The possible mechanism for the formation of gamma-lactams is also presented. (c) 2007 Elsevier B.V. All rights reserved