Chemoselective N-Acylation via Condensations of N-(Benzoyloxy)amines and α-Ketophosphonic Acids under Aqueous Conditions

• Published in: Journal of organic chemistry 2008-08, Vol.73 (16), p.6182-6186
• Main Authors: Arora, Jasbir Singh, Kaur, Navneet, IV, Otto Phanstiel
• Format: Article
• Language: English
• Subjects: Acylation; Aliphatic compounds; Amides - chemical synthesis; Amines - chemistry; Chemistry; Exact sciences and technology; Ketones - chemistry; Organic chemistry; Organophosphonates - chemistry; Preparations and properties; Water - chemistry
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo800223j

A new amide-forming reaction with N-benzoyloxyamines and α-ketophosphonic acids was investigated. A mixed solvent of t-BuOH/water (1:1) at 40 °C provided the desired amide in high yield (71−96%). Both phosphonic acids (9, 12, or 13) and their disodium salts (e.g., 10) were shown to react with the respective N-benzoyloxyamines (1b and 4) in excellent yields. The phosphonic acid methyl ester monosodium salt 11 did not react under these conditions. However, compound 11 did provide the desired amide in 22% yield upon addition of 2 equiv of TFA. The N-acylation reaction is highly chemoselective for N-benzoyloxyamines as both aliphatic amines and N-hydroxylamines were shown not to react productively with the α-ketophosphonic acids under the conditions tested. Moreover, the α-ketophosphonic acids are more selective than the related α-ketocarboxylic acid systems, which react with both the N-hydroxylamines and N-benzoyloxyamines. In this regard, this novel phosphonic acid methodology provides a new high-yielding, chemoselective acylating reagent for further study.