Bicyclic Pyrrolidines for Medicinal Chemistry via [3 + 2]-Cycloaddition.

A general approach to bicyclic fused pyrrolidines via [3 + 2]-cycloaddition between nonstabilized azomethyne ylide and endocyclic electron-deficient alkenes was elaborated. "Push-pull" alkenes and CF-alkenes did not react with the azomethyne ylide under the previously reported conditions, and we developed a superior protocol (LiF, 140 °C, no solvent). Among obtained products were medchem-relevant bicyclic sulfones, monofluoro-, difluoro-, and trifluoromethyl-substituted pyrrolidines.

Sulfonimidamides and Imidosulfuric Diamides: Compounds from an Underexplored Part of Biologically Relevant Chemical Space.

Two novel solid reagents-1-sulfonimidoyl- and 1-sulfamimidoyl-3-methylimidazolium derivatives-for the synthesis of sulfonimidamides and imidosulfuric diamides, respectively, were developed. It is shown that these reagents are very effective in substitution reactions with various N- and O-nucleophiles; therefore, they significantly extend the accessibility to the chemical space covered by organosulfur(VI) compounds with S=N bonds. In addition, previously unknown imidosulfuric diamides with free imino nitrogen groups were prepared, and their physical and chemical properties were characterized (including molecular geometry, pK , Log P, microsomal stability, and reactivity towards typical electrophiles).

New three-step domino reaction, "thiophilic addition-beta-elimination of fluoride-[3,3] sigmatropic rearrangement": Synthesis of alpha-allylic and alpha,alpha-bis(allylic) alpha-trifluoromethyl dithioesters.

The three-step domino reaction, "thiophilic addition of an organomagnesium reagent onto dithioester-beta-elimination of fluoride-[3,3] sigmatropic rearrangement", provides the product of formal regiospecific substitution of a fluorine atom by an allyl group. This mild and versatile methodology was applied to the synthesis of various alpha-allylic and alpha,alpha-bis(allylic) alpha-trifluoromethyl dithioesters.

Synthesis of a new polyfluorinated vinylogue of tetrathiafulvalene through 1,3-dipolar cycloaddition of ethyl beta-bromoperfluorodithiocrotonate with dimethyl acetylenedicarboxylate.

The ethyl ester of beta-bromoperfluorodithiocrotonic acid reacts with dimethyl acetylenedicarboxylate to give 1,4-difluoro-2,3-bis(trifluoromethyl)-but-2-ene-1,4-diylidene-2,2'-bis(4',5'-dicarbomethoxy-1',3'-dithiole) (4), a new type of vinylogue of tetrathiafulvalene. The thermal transformations of this compound lead, depending on the temperature, to the formation of the cyclization products: 11,14-difluoro-2,3,8,9-tetra(carbomethoxy)-12,13-bis(trifluoromethyl)-1,4,7,10-tetrathiadispiro[4.0.