Tandem nucleophilic addition-intramolecular aza-Michael reaction: facile synthesis of chiral fluorinated isoindolines.

A highly stereoselective synthesis of fluorinated 1,3-disubstituted isoindolines is described. To this end, a tandem reaction consisting of a diastereoselective addition of fluorinated nucleophiles to Ellman's N-(tert-butanesulfinyl)imines followed by an intramolecular aza-Michael reaction has been developed. This strategy allows for the construction of isoindolines bearing several degrees of fluorination (mono-, di-, or trifluoromethyl as well as heavier fluorinated groups). In the majority of all cases, the products are formed as single isomers.