Abstract
It is well established that the N-nitrosoamide derived from peracetylated derivatives of N-acetyl neuraminic acid on treatment with a mixture of sodium isopropoxide and trifluoroethanol, followed by the addition of acetic acid, gives an oxidative deamination product, in which the AcN(NO)-C5 bond is replaced with a AcO-C5 bond with the retention of configuration, affording a practical synthesis of 2-keto-3-deoxy-D-glycero-D-galactononulosonic acid (KDN) derivatives. Application of other strong acids, including hydrogen fluoride, thioacetic acid, trifluoromethanesulfonic acid, and hydrogen azide, functions similarly to afford KDN derivatives functionalized at the 5-position. We describe our attempts to extend the range of useful nucleophiles employed in this oxidative deamination process to include phenols and thiophenols, resulting in the discovery of a new branch of the general reaction and the formation of a series of products resulting from substitution of the S-acetamido group and of the 4-acetoxy group from neuraminic acid. A mechanistic rationale for the formation of these products is advanced according to which, in the absence of acids of pK(a) <= 8, the intermediate diazonium ion resulting from the elimination of acetic acid and nitrogen from the nitrosoacetamide undergoes elimination of acetic acid from the 4-position to afford a highly electrophilic alkenediazonium ion. Reversible conjugate addition of the nucleophile to the 4-position then initiates the reaction cascade leading to the ultimate products.