DIRECTED ORTHO METALATIONS OF TERTIARY BENZAMIDES USING LACTONES AS ELECTROPHILES

The efficient and regiospecific synthesis of polysubstituted aromatic compounds has been aided significantly by the advances made in the use of directed ortho metalation reactions. This approach involves deprotonation of a site ortho to a heteroatom-containing directed metalating group (DMG) by a strong base, normally an alkyllithium reagent, leading to an ortho-lithiated species which upon treatment with electrophilic reagents yield 1,2-disubstituted products.(1) The addition of a range of carbon electrophiles has been investigated including ketones, aldehydes, acyl halides and alkyl halides, carbamoyl chlorides, carbon dioxide and dimethyl formamide. Ester and lactone electrophiles have been less widely used.(1) In the latter case only a few examples have been reported using lactones derived from a carbohydrate with the use of an ether as the directed metalating group.(2,3)