Synthesis of carboxylic amides by ring-opening of oxazolidinones with Grignard reagents

Treatment of N-alkyl-oxazolidin-2-ones with Grignard reagents gives tertiary carboxylic amide products. Various substituted oxazolidinones can be used as illustrated with phenyl, benzyl or isopropyl groups on the 4-position, and methyl, benzyl or p-methoxybenzyl groups on the 3-position (the nitrogen atom). A selection of Grignard reagents were successful, including allyl, benzyl, alkyl and phenyl magnesium halides. The organomagnesium species attacks the carbonyl group and promotes ring-opening of the oxazolidinone. The product tertiary amides are useful substrates for stereoselective transformations and were applied to a highly selective enolate alkylation and to a ring-closing metathesis reaction to a six-membered lactam and hence a formal synthesis of the alkaloids (-)-coniine and (+)-stenusine.