Chemoselective Amide Formation Using O-(4-Nitrophenyl)hydroxylamines and Pyruvic Acid Derivatives
Abbreviated Journal Title
J. Org. Chem.
SELECTIVE REDUCING AGENT; ALPHA-KETOACIDS; BIOLOGICAL EVALUATION; O-ARYLHYDROXYLAMINES; N-(BENZOYLOXY)AMINES; CHEMISTRY; MECHANISM; CONDENSATIONS; MYCOBACTERIA; REDUCTION; Chemistry, Organic
A series of O-(4-nitrophenyl)hydroxylamines were synthesized from their respective oximes using a pulsed addition of excess NaBH3CN at pH 3 in 65-75% yield. Steric hindrance near the oxime functional group played a key role in both the ease by which the oxime could be reduced and the subsequent reactivity of the respective hydroxylamine. Reaction of the respective hydroxylamines with pyruvic acid derivatives generated the desired amides in good yields. A comparison of phenethylamine systems bearing different leaving groups revealed significant differences in the rates of these systems and suggested that the leaving group ability of the N-OR substituent plays an important role in determining their reactivity with pyruvic acid. Competition experiments (in 68% DMSO/phosphate buffered saline) using 1 equiv of N-phenethyl-O-(4-nitrophenyl)hydroxylamine and 2 equiv of pyruvic acid in the presence of other nucleophiles such as glycine, cysteine, phenol, hexanoic acid, and lysine demonstrated that significant chemoselectivity is present in this reaction. The results suggest that this chemoselective reaction can occur in the presence of excess alpha-amino acids, phenols, acids, thiols, and amines.
Journal of Organic Chemistry
"Chemoselective Amide Formation Using O-(4-Nitrophenyl)hydroxylamines and Pyruvic Acid Derivatives" (2012). Faculty Bibliography 2010s. 2895.