Selective Reaction of Glycine Residues in Hydrogen Atom Transfer from Amino Acid Derivatives

Article abstract of DOI:10.1021/ja00185a039

Relative rates of reaction of the N-benzoylamino acid methyl esters 1a-4a with N-bromosuccinimide and of 1a-4a with di-tert-butyl peroxide are reported.The selective reaction of glycine derivatives in these and other reactions of N-acylamino acid derivatives is attributed to the relative stability of intermediate radicals produced by hydrogen atom transfer.Radicals formed by hydrogen abstraction from N-acylglycine derivatives may adopt planar conformations which are relatively free of nonbonding interactions and in which there is maximum delocalization of the unpairedelectron, whereas radicals produced by similar reactions of derivatives of other amino acids are relatively unstable because of nonbonding interactions.In accord with this hypothesis, methyl pyroglutamate (5a) reacts at a faster rate than N-benzoylglycine methyl ester (1a) in reactions with either N-bromosuccinimide or di-tert-butyl peroxide.Anomalous rates of reaction of N-benzoylproline methyl ester (6a) are rationalized in terms of the regioselectivity of hydrogen atom transfer.Evidence for the mechanisms of reactions of 1a-6a is derived from product studies and by comparison of the relative rates of reactions of 1a-6a with those of the deuteriated amino acid derivatives 1b, 2b, 3b,c, 5b, and 6b,c.