Mechanistic Evidence for an -Oxoketene Pathway in the Formation of 
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- 作者：Feng Xu ; Joseph D. Armstrong III ; George X. Zhou ; Bryon Simmons ; David Hughes ; Zhihong Ge ; and Edward J. J. Grabowski
- 刊名：Journal of the American Chemical Society
- 出版年：2004
- 出版时间：October 13, 2004
- 年：2004
- 卷：126
- 期：40
- 页码：13002 - 13009
- 全文大小：183K
- 年卷期：v.126,no.40(October 13, 2004)
- ISSN：1520-5126
文摘
A practical, one-pot process for the preparation of 
-keto amides via a three-component reaction,including Meldrum's acid, an amine, and a carboxylic acid, has been developed. Key to development of anefficient, high-yielding process was an in-depth understanding of the mechanism of the multistep process.Kinetic studies were carried out via online IR monitoring and subsequent principal component analysiswhich provided a means of profiling the concentration of both the anionic and free acid forms of the Medrum'sadduct 6 in real time. These studies, both in the presence and absence of nucleophiles, strongly suggestthat formation of -keto amides from acyl Meldrum's acids occurs via 
-oxoketene species 2 and rule outother possible reaction pathways proposed in the literature, such as via protonated -oxoketeneintermediates 3 or nucleophilic addition-elimination pathways.
-keto amides via a three-component reaction,including Meldrum's acid, an amine, and a carboxylic acid, has been developed. Key to development of anefficient, high-yielding process was an in-depth understanding of the mechanism of the multistep process.Kinetic studies were carried out via online IR monitoring and subsequent principal component analysiswhich provided a means of profiling the concentration of both the anionic and free acid forms of the Medrum'sadduct 6 in real time. These studies, both in the presence and absence of nucleophiles, strongly suggestthat formation of -keto amides from acyl Meldrum's acids occurs via -oxoketene species 2 and rule outother possible reaction pathways proposed in the literature, such as via protonated -oxoketeneintermediates 3 or nucleophilic addition-elimination pathways.