O-Methylarenehydroxamates as ortho-lithiation directing groups. Titanium(III)-mediated conversion of O-methyl hydroxamates to primary amides

Abstract

Reaction of O-methyl benzohydroxamates 2a-c with sec-butyllithium in the presence of TMEDA at -40 o C regiospecifically generates the highly reactive N,ortho-dilithiated species (e.g. 3). These dilithio species react avidly with a wide spectrum of electrophilic reagents, including allyl halides, giving adducts which on reduction with TiCl 3 are converted into ortho-substituted primary benzamides in excellent yields. Ortho lithiation of O-methyl benzohydroxamates is thus formally equivalent to ortho lithiation of primary benzamides themselves. The utility of these synthetic operations is enhanced by the well-known facility with which the primary amide moiety can be transformed into other useful functional groups