Synthesis of stereocontrolled α,α-difluoro-β-hydroxycarbonyl materials

Synthesis and chemistry of α-iodoperfluoroacid esters

“…1 Reaction of ethyl heptafluorobutyrate (1) to give ethyl aiodohexafluorobutyrate (2) is a representative example. Under our conditions, (1) the iododefluorination is about 60% complete after 24 h, but requires 4 days for complete conversion and a 90% yield (by NMR). Because of their solubility in both water and organic solvents, the tetrabutylammonium salts in the reaction mixture complicate the workup.…”

“…Yield of dimethyl 2-iodoperfluoroadipate: 0.30 g, 39%. 1 2962, 1763, 1438, 1289, 1254, 1155, 1118. The other isomer of dimethyl 2,5-diiodoperfluoroadipate (smaller R f on silica gel) was contaminated with dimethyl 2-iodoperfluoroadipate.…”

“…The other isomer of dimethyl 2,5-diiodoperfluoroadipate (smaller R f on silica gel) was contaminated with dimethyl 2-iodoperfluoroadipate. 1 Methyl perfluoro-2-iodopropionate (17) (1.0 g, 3.5 mmol) was dissolved in ethanol/water solution (1:1, 5 mL). Potassium hydroxide (0.23 g, 3.5 mmol) was dissolved in the same solvent (5 mL), and it was added dropwise to the ester solution.…”

“…One of the most important transformations of these compounds is the Reformatsky reaction, which yields b-hydroxy esters [1]. A variation on this reaction entails prior conversion to O-silylketene acetals [2], from which chiral b-hydroxy esters have been obtained [3].…”

Palladium-Catalyzed Carbonylative Cross-Coupling of Difluoroalkyl Halides with Alkylboranes under 1 atm of CO

“…2 As a consequence, it is of great interest to access such a valuable fluorinated motif. Traditionally, two common methods are used to prepare alkyldifluoroalkyl ketones: one is based on the nucleophilic addition of α,α-difluoro carboxylic acid amides with organolithium or Grignard reagents; 3 the other relies on the oxidation of α,α-difluorinated alcohols. 4 However, the former method suffers from the limited substrate scope and poor functional group tolerance, and the latter requires a multistep synthetic procedure to prepare the corresponding alcohols, thus significantly restricting their widespread synthetic applications.…”