A research team led by Prof. WU Xiaofeng from the Dalian Institute of Chemical Physics (DICP) of the Chinese Academy of Sciences (CAS) has realized the palladium-catalyzed difluoroalkylative carbonylation of styrenes toward difluoropentanedioates.
This study was published in Chemical Science on August 3.
Organic fluorides play an important role in organic synthesis, especially in medicinal chemistry and materials science. Among them, difluoromethylene has good metabolic stability, and its electron-absorbing property can affect the electronic and chemical properties of adjacent functional groups, thus it is present in a variety of drug molecules and bioactive molecules.
However, the fluoroalkylation carbonylation of aryl olefins remains a challenge due to their strong tendency to oligometrize and polymerize.
In this study, the researchers developed a new method for carbonylation of aryl olefins by palladium-catalyzed difluoroalkylation.
They used inexpensive industrial reagent ethyl bromodifluoroacetate both as a difluorinated precursor and as a nucleophilic reagent, and converted a variety of aryl olefins to the corresponding difluoroglutaryl compounds in good yields, with broad functional group tolerance and excellent selectivity.
The reaction could be scaled up to 3 mmol, and the product difluoroglutarate compounds could be efficiently converted to the corresponding diacids and diols. (Text by BAO Zhipeng)