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Communication

A Highly Enantioselective Amino Acid-Catalyzed Route to Functionalized α-Amino Acids

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Armando Córdova, Wolfgang Notz, Guofu Zhong, Juan M. Betancort, and Carlos F. Barbas III*

The Skaggs Institute for Chemical Biology and the Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, California 92037

J. Am. Chem. Soc., 2002, 124 (9), pp 1842–1843

DOI: 10.1021/ja017270h

Publication Date (Web): February 8, 2002

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

Abstract

The development of syntheses providing enantiomerically pure α-amino acids has intrigued generations of chemists and been the subject of intense research. This report describes a general approach to functionalized α-amino acids based on catalytic asymmetric synthesis. Proline catalyzed Mannich-type reactions of N-PMP-protected α-imino ethyl glyoxylate with a variety of unmodified ketones to provide functionalized α-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.

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Published In Issue March 06, 2002
Received October 9, 2001

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Communication

A Highly Enantioselective Amino Acid-Catalyzed Route to Functionalized α-Amino Acids

Abstract

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History

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Related Content

A Highly Enantioselective Route to Either Enantiomer of Both α- and β-Amino Acid Derivatives

The Proline-Catalyzed Direct Asymmetric Three-Component Mannich Reaction: Scope, Optimization, and Application to the Highly Enantioselective Synthesis of 1,2-Amino Alcohols

Direct Catalytic Asymmetric Synthesis of anti-1,2-Amino Alcohols and syn-1,2-Diols through Organocatalytic anti-Mannich and syn-Aldol Reactions

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