Alexander D. Dilman

Reactions of Difluorocarbene with Organozinc Reagents

Reactions of difluorocarbene with benzyl and alkylzinc halides leading to fluorinated organozinc species have been described. The generated α-difluorinated organozinc reagents are reasonably stable in solution and can be quenched with external electrophiles (iodine, bromine, proton), affording compounds containing the CF(2) fragment.

Difluoromethylene Phosphabetaine as an Equivalent of Difluoromethyl Carbanion

A method for nucleophilic difluoromethylation of reactive Michael acceptors, aldehydes, and azomethines is described. The reaction is performed using the readily available and air-stable reagent difluoromethylene phosphabetaine. The process involves interaction of an electrophilic substrate with in situ generated difluorinated phosphonium ylide followed by hydrolysis of the carbon-phosphorus bond under mild conditions.

Difluoro(trimethylsilyl)acetonitrile: synthesis and fluoroalkylation reactions.

A new silicon reagent, difluoro(trimethylsilyl)acetonitrile, was prepared by insertion of difluorocarbene into silyl cyanide. The obtained silane served as a good cyanodifluoromethylating reagent toward aldehydes, N-tosylimines, N-alkylimines, and enamines under basic or acidic conditions.

Difluorohomologation of Ketones

A method for the homologation of ketones with the CF2 fragment is described. The reaction involves silylation, room-temperature difluorocyclopropanation of silyl enol ethers, and selective ring opening of cyclopropanes under acidic conditions. The whole three-step sequence is conveniently performed in a one-pot mode.

Reactions of Sulfur- and Phosphorus-Substituted Fluoroalkylating Silicon Reagents with Imines and Enamines under Acidic Conditions

Nucleophilic fluoroalkylation reactions of imines and enamines with α-phenylthio, α-phenylsulfonyl, and α-diethylphosphoryl substituted fluorinated silanes have been investigated. The reactions are promoted by hydrofluoric acid generated in situ from potassium hydrodifluoride and trifluoroacetic acid. Sulfur reagents worked well with both imines and enamines, whereas phosphorus reagent efficiently coupled only with enamines.

Geminal Silicon/Zinc Reagent as an Equivalent of Difluoromethylene Bis-carbanion

A new difluorinated reagent, [difluoro(trimethylsilyl)methyl]zinc bromide, bearing C-Zn and C-Si bonds is described. The reagent is conveniently prepared by cobalt-catalyzed halogen/zinc exchange. It can be coupled with two different C-electrophiles in a stepwise manner (with allylic halides for C-Zn bond and aldehydes for C-Si bond) affording products containing a difluoromethylene fragment.

Copper-Catalyzed Allylation of α,α-Difluoro-Substituted Organozinc Reagents

A method for the coupling of organozinc reagents, difluorocarbene, and allylic electrophiles is described. The reaction involves insertion of difluorocarbene into the carbon-zinc bond followed by copper-catalyzed allylic substitution.

Nucleophilic bromo- and iododifluoromethylation of aldehydes.

A method for bromo- and iododifluoromethylation of aldehydes using bromo- and iodo-substituted difluoromethyl silicon reagents (Me(3)SiCF(2)X) is described. The reaction is performed in the presence of a combination of tetrabutylammonium and lithium salts Bu(4)NX/LiX (X = Br or I) in propionitrile. It is believed that, in this process, a short-lived halodifluoromethyl carbanion serves as nucleophile, which is reversibly generated from difluorocarbene and a halide anion.

Trifluoromethylation of N-Benzoylhydrazones

A method for the nucleophilic trifluoromethylation of N-benzoylhydrazones using Me3SiCF3/AcONa has been described. The CN bond of the hydrazones is activated by difluoroboron group, which is introduced by means of boron trifluoride and allylsilane.

Nucleophilic Bromodifluoromethylation of Iminium Ions

A method for bromodifluoromethylation of iminium ions using Me3SiCF2Br is described. The reaction involves room temperature activation of the silicon reagent by HMPA to generate difluorocarbene, which upon interacting with excess of bromide ion provides bromodifluoromethyl carbanionic species. The iminium electrophiles are generated in situ from aldehydes, secondary amines, proton sponge, and silyl triflate. The reaction can be extended for introduction of chlorodifluoromethyl and iododifluoromethyl groups.