Enantioselective synthesis of (3S)-trans-4-(substituted methyl)monobactams from 2,3-O-isopropylidene-D-glyceraldehyde

The enantioselective synthesis of various (3S)-trans-4-(substituted methyl)-2-oxoazetidine-1-sulphonic acid derivatives from 2,3-O-isopropylidene-D-glyceraldehyde is described. Reaction of this aldehyde with trimethylsilyl cyanide gave a 80:20 ratio of the corresponding threo and erythroα-aminonitriles, which by amino protection and subsequent treatment with basic hydrogen peroxide provided the corresponding α-amino carboxamides. Successive selective protection, activation, sulphonation and, finally, stereospecific cyclization of the threoα-carboxamide yielded (2S,4R)-3-benzyloxycarbonylamino-4-hydroxymethyl-2-oxoazetidine-1-sulphonic acid, an intermediate for the synthesis of the corresponding 4-acyloxymethyl-, 4-carbamoyloxymethyl-, 4-methylsulphonyloxymethyl-, 4-iodomethyl-, and 4-methyl-2-oxozetidines.