Metalation of o-methylanisole (o-MA); an optional-site selectivity reassessment

‘Deficiency catalysis’ is the concept applied to metalation chemistry that increments of TMEDA or an equivalent or two of an ether activate alkyllithiums in hydrocarbon media. Amplification of this concept to conflicting reports of α- and ortho-metalation of ortho-methylanisole (o-MA) is explored. Both regioselective metalations were realized in selectivity ratios of >7:1 for the desired isomers. Some rationale is provided for the various selectivities. These results are at variance with prior results and interpretations thereof found in the literature.