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. 2024 Jan 10;29(2):342.
doi: 10.3390/molecules29020342.

Phosphine Catalyzed Michael-Type Additions: The Synthesis of Glutamic Acid Derivatives from Arylidene- α-amino Esters

Lesly V Rodríguez-Flórez  1 , María González-Marcos  1 , Eduardo García-Mingüens  2 , María de Gracia Retamosa  1 , Misa Kawase  1 , Elisabet Selva  2 , José M Sansano  1
Affiliations

Phosphine Catalyzed Michael-Type Additions: The Synthesis of Glutamic Acid Derivatives from Arylidene- α-amino Esters

Lesly V Rodríguez-Flórez et al. Molecules. .

Abstract

The reaction of arylidene-α-amino esters with electrophilic alkenes to yield Michael-type addition compounds is optimized using several phosphines as organocatalysts. The transformation is very complicated due to the generation of several final compounds, including those derived from the 1,3-dipolar cycloadditions. For this reason, the selection of the reaction conditions is a very complex task and the slow addition of the acrylic system is very important to complete the process. The study of the variation in the structural components of the starting imino ester is performed as well as the expansion of other electron-poor alkenes. The crude products have a purity higher than 90% in most cases without any purification. A plausible mechanism is detailed based on the bibliography and the experimental results. The synthesis of pyroglutamate entities, after the reduction of the imino group and cyclization, is performed in high yields. In addition, the hydrolysis of the imino group, under acidic media, represents a direct access to glutamate surrogates.

Keywords: Michael addition; glutamates; imino esters; organocatalysis; phosphines; pyroglutamates.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Scheme 1
Scheme 1
(a–c) Strategies for the preparation of glutamate derivatives.
Scheme 2
Scheme 2
Optimization of the Michael-type addition of imino ester 1a onto methyl acrylate (MA).
Scheme 3
Scheme 3
Mechanism of the formation of products 2a, 3a, 4 and 5.
Scheme 4
Scheme 4
Scope of the Michael-type addition of imino esters 1 onto alkyl acrylates.
Scheme 5
Scheme 5
Michael-type addition of imino ester 1g onto AN and PVS.
Scheme 6
Scheme 6
Synthesis of pyroglutamate derivatives 8. (a) From compounds 2. (b) From compounds 1 without isolating intermediate molecules 2.
Scheme 7
Scheme 7
Synthesis of glutamate derivative 9.
See this image and copyright information in PMC

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