A hexafluoroisopropanol (HFIP)-promoted hydroxydifluoromethylation of aniline, indole, and pyrrole derivatives with difluoroacetaldehyde ethyl hemiacetal has been developed. This protocol provides a facile and straightforward approach to access diverse difluoromethylated carbinols in good to excellent yields under mild conditions. Furthermore, gram-scale and synthetic derivatization experiments have also been demonstrated.

A HFIP-promoted highly selective hydroxyalkylation of aniline derivatives with arylglyoxal hydrates has been realized. The reaction produces various N,N-dialkylanilines and their derivatives with α-hydroxy carbonyl units in good to excellent yields under mild conditions. Furthermore, the synthetic potential of this method has been demonstrated by the facile synthesis of several structurally interesting molecules such as benzil, 1,2,4-triazine, quinoxaline, hydantoin, and 2-thiohydantoin with aromatic amine units.

A novel efficient HFIP-catalyzed synthesis of structurally diverse 2,2-difluoro-3-hydroxy-1,4-diketone derivatives from readily available glyoxal monohydrates and difluoroenoxysilanes is described. This convenient protocol is induced by the distinctive fluorine effect of the reactants and the fluoroalcohol catalyst, which represents the first application of fluoroalcohol catalysis in a Mukaiyama aldol reaction.

A convenient approach for the synthesis of 3-difluoroalkyl phthalides has been developed from phthalaldehydic acids and difluoroenoxysilanes by using relatively inexpensive p-toluenesulfonic acid monohydrate (PTSA) as a catalyst. A series of 3-difluoroalkyl phthalides and cyclic difluoroalkyl ethers were obtained in up to 99% yield. The products obtained could be readily converted into difluoroalkyl phthalide derivatives by simple modifications.