Title

Chemoselective Amide Formation Using O-(4-Nitrophenyl)hydroxylamines and Pyruvic Acid Derivatives

Authors

Authors

S. Kumar; R. Sharma; M. Garcia; J. Kamel; C. McCarthy; A. Muth;O. Phanstiel

Comments

Authors: contact us about adding a copy of your work at STARS@ucf.edu

Abbreviated Journal Title

J. Org. Chem.

Keywords

SELECTIVE REDUCING AGENT; ALPHA-KETOACIDS; BIOLOGICAL EVALUATION; O-ARYLHYDROXYLAMINES; N-(BENZOYLOXY)AMINES; CHEMISTRY; MECHANISM; CONDENSATIONS; MYCOBACTERIA; REDUCTION; Chemistry, Organic

Abstract

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 Title

Journal of Organic Chemistry

Volume

77

Issue/Number

23

Publication Date

1-1-2012

Document Type

Article

Language

English

First Page

10835

Last Page

10845

WOS Identifier

WOS:000311926100038

ISSN

0022-3263

Share

COinS