gem-Difluoroolefination of Amides.

A metal-free one-pot process for the gem-difluoroolefination of amides is described. The reaction is based on interaction of generated in situ α-chloroiminium salts with difluorinated phosphorus ylide formed from difluorocarbene and triphenylphosphine. The olefination involves nucleophile-assisted dephosphorylation and proceeds within one hour at low temperature. The gem-difluoroenamines were used in further transformations leading to a variety of fluoroalkylated amines.

Synthesis of Difluoroalkylated Heteroarenes via Difluorocarbene.

A diversity-oriented and C2-selective synthesis of difluoroalkyl-substituted heteroarenes from three fragments, N-methoxyazinium salts, difluorocarbene, and electrophilic or radical reagents, is described. The reaction proceeds via the addition of difluorinated phosphorus ylide to in situ methylated heteroarene N-oxides, leading to phosphonium salts, which can undergo further transformations under basic or photoinduced conditions.

Visible-Light-Promoted Iododifluoromethylation of Alkenes via (Phosphonio)difluoromethyl Radical Cation.

A reaction of an iododifluoromethylphosphonium salt with unactivated alkenes mediated by peri-xanthenoxanthene under blue-light irradiation is described. The reaction proceeds via activation of the carbon-iodine bond to generate (phosphonio)difluoromethyl radical cation, which attacks the double bond with subsequent quenching by the iodine. The intermediate phosphonium salts are easily hydrolyzed, furnishing products of iododifluoromethylation of alkenes.

Difluoromethylation of Carboxylic Acids via the Addition of Difluorinated Phosphorus Ylide to Acyl Chlorides.

A one-step protocol for the difluoromethylation of carboxylic acids is described. The reaction involves the interaction of intermediate acyl chlorides with in situ generated difluorinated phosphorus ylide Ph3P═CF2. Aromatic acids can be selectively transformed within one step either to bis-difluoromethylated alcohols or to difluorinated ketones depending on the particular reaction conditions. For bulky α-branched carboxylic acids, only ketones are produced.

Nucleophilic Difluoromethylation Using (Bromodifluoromethyl)trimethylsilane.

A combination of (bromodifluoromethyl)trimethylsilane (Me3SiCF2Br), triphenylphosphine, and DMPU serves as a source of difluorinated phosphorus ylide Ph3P═CF2 under mild conditions. The system was used to effect nucleophilic difluoromethylation of ketones and nitro alkenes. The reaction efficiency is believed to be associated with Lewis acidic activation of the substrates by a silylium species formed upon generation of the phosphorus ylide.

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.