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

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• 作者：Sonali Kumar ; Rashi Sharma ; Megan Garcia ; Joseph Kamel ; Caroline McCarthy ; Aaron Muth ; Otto Phanstiel ; IV
• 刊名：The Journal of Organic Chemistry
• 出版年：2012
• 出版时间：December 7, 2012
• 年：2012
• 卷：77
• 期：23
• 页码：10835-10845
• 全文大小：393K
• 年卷期：v.77,no.23(December 7, 2012)
• ISSN：1520-6904

文摘

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鈥?5% 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鈥揙R 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 伪-amino acids, phenols, acids, thiols, and amines.