A Highly Enantioselective Amino Acid-Catalyzed Route to Functionalized -Amino Acids
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- 作者：Armando Có ; rdova ; Wolfgang Notz ; Guofu Zhong ; Juan M. Betancort ; and Carlos F. Barbas ; III
- 刊名：Journal of the American Chemical Society
- 出版年：2002
- 出版时间：March 6, 2002
- 年：2002
- 卷：124
- 期：9
- 页码：1842 - 1843
- 全文大小：39K
- 年卷期：v.124,no.9(March 6, 2002)
- ISSN：1520-5126
文摘
The development of syntheses providing enantiomerically pure 
-amino acids has intrigued generations of chemists and been the subject of intense research. This report describes a general approach to functionalized -amino acids based on catalytic asymmetric synthesis. Proline catalyzed Mannich-type reactions of N-PMP-protected -imino ethyl glyoxylate with a variety of unmodified ketones to provide functionalized -amino acids in high yields with excellent regio-, diastereo-, and enantioselectivities. Study of seven examples yielded six with product ee values of 
99%. In reactions involving ketone donors where diastereoisomeric products could be formed, two adjacent stereogenic centers were created simultaneously upon carbon-carbon bond formation with complete syn-stereocontrol. Significantly, this methodology utilizes readily available and rather inexpensive starting materials, does not require any preactivation of substrates or metal ion assistance, and can be carried out on a gram scale under operationally simple reaction conditions. The keto-functionality present in the products provides a particularly attractive site for versatile modifications. This study compliments and extends our bioorganic approach to asymmetric synthesis to a versatile synthon class. Given that we have shown that a variety of optically active amino acids can be synthesized with proline catalysis, where an L-amino acid begets other L-amino acids, our results may stimulate thoughts concerning prebiotic syntheses of optically active amino acids based on this route.
-amino acids has intrigued generations of chemists and been the subject of intense research. This report describes a general approach to functionalized -amino acids based on catalytic asymmetric synthesis. Proline catalyzed Mannich-type reactions of N-PMP-protected -imino ethyl glyoxylate with a variety of unmodified ketones to provide functionalized -amino acids in high yields with excellent regio-, diastereo-, and enantioselectivities. Study of seven examples yielded six with product ee values of 99%. In reactions involving ketone donors where diastereoisomeric products could be formed, two adjacent stereogenic centers were created simultaneously upon carbon-carbon bond formation with complete syn-stereocontrol. Significantly, this methodology utilizes readily available and rather inexpensive starting materials, does not require any preactivation of substrates or metal ion assistance, and can be carried out on a gram scale under operationally simple reaction conditions. The keto-functionality present in the products provides a particularly attractive site for versatile modifications. This study compliments and extends our bioorganic approach to asymmetric synthesis to a versatile synthon class. Given that we have shown that a variety of optically active amino acids can be synthesized with proline catalysis, where an L-amino acid begets other L-amino acids, our results may stimulate thoughts concerning prebiotic syntheses of optically active amino acids based on this route.