Phosphine Catalyzed Michael-Type Additions: The Synthesis of Glutamic Acid Derivatives from Arylidene-<i>α</i>-amino Esters
The reaction of arylidene-<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi mathvariant="sans-serif">α</mi></semantics></math></inline-formula>-amino esters with electrophilic...
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| Format: | Article |
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MDPI AG
2024-01-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/29/2/342 |
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| author | Lesly V. Rodríguez-Flórez María González-Marcos Eduardo García-Mingüens María de Gracia Retamosa Misa Kawase Elisabet Selva José M. Sansano |
| author_facet | Lesly V. Rodríguez-Flórez María González-Marcos Eduardo García-Mingüens María de Gracia Retamosa Misa Kawase Elisabet Selva José M. Sansano |
| author_sort | Lesly V. Rodríguez-Flórez |
| collection | DOAJ |
| description | The reaction of arylidene-<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi mathvariant="sans-serif">α</mi></semantics></math></inline-formula>-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. |
| first_indexed | 2024-03-08T09:49:45Z |
| format | Article |
| id | doaj.art-745e8a8584c74ba193664604de69f768 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-08T09:49:45Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-745e8a8584c74ba193664604de69f7682024-01-29T14:07:42ZengMDPI AGMolecules1420-30492024-01-0129234210.3390/molecules29020342Phosphine Catalyzed Michael-Type Additions: The Synthesis of Glutamic Acid Derivatives from Arylidene-<i>α</i>-amino EstersLesly V. Rodríguez-Flórez0María González-Marcos1Eduardo García-Mingüens2María de Gracia Retamosa3Misa Kawase4Elisabet Selva5José M. Sansano6Departamento de Química Orgánica, Centro de Innovación en Química Avanzada (ORFEO-CINQA) and Instituto de Síntesis Orgánica, Universidad de Alicante, Ctra. Alicante-San Vicente s/n, 03080 Alicante, SpainDepartamento de Química Orgánica, Centro de Innovación en Química Avanzada (ORFEO-CINQA) and Instituto de Síntesis Orgánica, Universidad de Alicante, Ctra. Alicante-San Vicente s/n, 03080 Alicante, SpainMedalchemy, S. L. Ancha de Castelar, 46-48, entlo. A. San Vicente del Raspeig, 03690 Alicante, SpainDepartamento de Química Orgánica, Centro de Innovación en Química Avanzada (ORFEO-CINQA) and Instituto de Síntesis Orgánica, Universidad de Alicante, Ctra. Alicante-San Vicente s/n, 03080 Alicante, SpainDepartamento de Química Orgánica, Centro de Innovación en Química Avanzada (ORFEO-CINQA) and Instituto de Síntesis Orgánica, Universidad de Alicante, Ctra. Alicante-San Vicente s/n, 03080 Alicante, SpainMedalchemy, S. L. Ancha de Castelar, 46-48, entlo. A. San Vicente del Raspeig, 03690 Alicante, SpainDepartamento de Química Orgánica, Centro de Innovación en Química Avanzada (ORFEO-CINQA) and Instituto de Síntesis Orgánica, Universidad de Alicante, Ctra. Alicante-San Vicente s/n, 03080 Alicante, SpainThe reaction of arylidene-<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi mathvariant="sans-serif">α</mi></semantics></math></inline-formula>-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.https://www.mdpi.com/1420-3049/29/2/342organocatalysisphosphinesimino estersMichael additionglutamatespyroglutamates |
| spellingShingle | Lesly V. Rodríguez-Flórez María González-Marcos Eduardo García-Mingüens María de Gracia Retamosa Misa Kawase Elisabet Selva José M. Sansano Phosphine Catalyzed Michael-Type Additions: The Synthesis of Glutamic Acid Derivatives from Arylidene-<i>α</i>-amino Esters Molecules organocatalysis phosphines imino esters Michael addition glutamates pyroglutamates |
| title | Phosphine Catalyzed Michael-Type Additions: The Synthesis of Glutamic Acid Derivatives from Arylidene-<i>α</i>-amino Esters |
| title_full | Phosphine Catalyzed Michael-Type Additions: The Synthesis of Glutamic Acid Derivatives from Arylidene-<i>α</i>-amino Esters |
| title_fullStr | Phosphine Catalyzed Michael-Type Additions: The Synthesis of Glutamic Acid Derivatives from Arylidene-<i>α</i>-amino Esters |
| title_full_unstemmed | Phosphine Catalyzed Michael-Type Additions: The Synthesis of Glutamic Acid Derivatives from Arylidene-<i>α</i>-amino Esters |
| title_short | Phosphine Catalyzed Michael-Type Additions: The Synthesis of Glutamic Acid Derivatives from Arylidene-<i>α</i>-amino Esters |
| title_sort | phosphine catalyzed michael type additions the synthesis of glutamic acid derivatives from arylidene i α i amino esters |
| topic | organocatalysis phosphines imino esters Michael addition glutamates pyroglutamates |
| url | https://www.mdpi.com/1420-3049/29/2/342 |
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