The introduction of fluorine(s) into bioactive molecules typically increases their metabolic stability, lipophilicity, bioavailability, permeability and binding affinity of bioactive molecules. An estimated 30-40% of all agrochemicals and 20% of pharmaceuticals contain fluorine.Oxindole derivatives are useful synthetic intermediates for the preparation of biologically active molecules. The replacement of the keto carbonyl in isatinswith the isosteric gem-difluoro moiety leads to 3,3-difluoroxindole, a useful analogue for biological studies. This is often synthesized directly by nucleophilic fluorination of isatinsusing the thermally unstable diaminosulfur trifluoride (DAST), or more recently,  bis(methoxyethyl)-aminosulfur trifluoride (Deoxofluor) and 4-tert-butyl-2,6-dimethylphenylsulfur trifluoride (Fluolead). Yet, there has been no report on the direct conversion of broadly available indoles to 3,3-difluoroxindoles  to-date. Herein, a convenient one-pot method for the synthesis of 3,3-difluorooxindoles from readily available indoles via electrophilic fluorination has been developed.

Direct synthesis of 3,3-difluorooxindoles from indoles via electrophilic fluorination

245th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.