NEW SYNTHESIS OF ALPHA-AMINO-ACID N-CARBOXY ANHYDRIDES THROUGH BAEYER-VILLIGER OXIDATION OF ALPHA-KETO BETA-LACTAMS

A conceptually new route for the generation of optically active alpha- aminoacid N-carboxy anhydrides (NCAs) and hence alpha-amino acid deriv atives is described. The strategy developed is simple and consists of the oxidation of alpha-hydroxy beta-lactams to the corresponding alpha -keto beta-lactams followed by a Baeyer-Villiger rearrangement. By tha t means, a wide variety of functionalized alpha-aminoacid N-carboxy an hydrides can be obtained, i.e., alpha,beta-diamino acid and alpha-amin o beta-hydroxy acid-derived NCAs. The starting alpha-hydroxy(alkoxy) b eta-lactams required for the study are easily prepared in large quanti ties either by the cycloaddition reaction of achiral alkoxyketenes wit h chiral aldehyde-derived imines or by the addition of Grignard reagen ts to a 3-(benzyloxy)-4-formylazetidin-2-one. The construction of a wi de variety of NCA's from non-amino acid precursors becomes the most re markable point of the reaction methodology developed.