{"id":{"repo_id":"aachen","oai_identifier":"oai:publications.rwth-aachen.de:61534"},"canonical_url":"https://search.dev.ndltd.org/etd/aachen/oai:publications.rwth-aachen.de:61534","repository":{"repo_id":"aachen","name":"RWTH Aachen University","base_url":"https://publications.rwth-aachen.de/oai2d"},"display":{"title":"Synthesis and reactivity of alpha-trialkylsilyl alpha-amino acids","abstract":"This work deals with the synthesis and reactivity of alpha-trialkylsilyl alpha-amino acids. They were synthesised using an established protocol involving rhodium(II)-catalysed insertion reactions of alpha-trialkylsilyl alpha-diazo esters into N-H bonds of carbamates. As an extension to this procedure, it was accounted that a diastereoselective approach to N-protected alpha-trialkylsilyl alpha-amino acids precursors may lead, after deprotection, to the formation of enantiomerically-pure alpha-trialkylsilyl alpha-amino acids. A variety of diastereoselective synthetic strategies were examinated. These investigations involved the use of alpha-trialkylsilyl alpha-keto-acetates as substrates, as well as various reactants such as chiral amines, ureas, or carbamates as sources of the chiral information. Carbamates were confirmed as the mostly efficient N-H sources for rhodium(II)-catalysed reaction. A diastereoselective N-H insertion reaction was attempted between a alpha-triethylsilyl alpha-diazo benzyl acetate and L-menthyl carbamate. The reaction proceeded in a diastereoselective formation of the N-H inserted product in a diastereomeric ratio of 75 to 25. A part of this project was then devoted to the synthesis of the racemic N-Cbz-protected 2-trimethylsilyl glycine. The possibility to obtain the free carboxylic functional group of the named compound from selective deprotection of a corresponding ester moiety was investigated. Various ester protecting groups were considered, the removal of which could give access to the free carboxylic acids and thus to enantiopure alpha-silyl alpha-amino acids through resolution by chemical methods. The most promising result was obtained when the 2-triethylsilyl-2-diazo-(4-methoxybenzyl) acetate underwent reaction with aluminum thrichloride/ethanthiol to yield to the mono-deprotected compound in a 1H NMR ratio 1.6 to 1 respect to the substrate. Attempts to selective removal of the benzyl ester moiety of N-Cbz-protected alpha-silyl alpha-amino benzyl acetate through selective hydrogenation remained unsuccessful. Hydrogenation over palladium(0) allowed exclusively the formation of the bi-deprotected alpha-silyl alpha-amino acetic acid. The alpha-silyl alpha-amino acid core could become a substructure of a more complicated structure, as for example of a modified Matrix metalloproteinase (MMP) inhibitor. Various synthetic strategies were considered and attempted towards the synthesis of the two building blocks of a silyl modified succinyl hydroxamic acid based MMPs inhibitor. The coupling of a iso-butyl succinyl hydroxamic acid (or the corresponding iso-propyl analogue) and the trifluoroacetic salt of 2-triethylsilyl-2-amino benzyl acetate using various coupling reagents, between them, PyBOP(R) combined with ethyldiisopropylamine, appeared the most promising. Finally, studies on microwave assisted synthesis of N-protected alpha-trialkylsilyl alpha-amino esters were described. A final summary of the several examples reported indicated a shortening of the reaction times under microwave irradiation in comparison to the same transformations performed under standard conditions and conventional heating. To these results, although, did not correspond a sensible enhancement of the chemo- and the stereoselectivity of the discussed reactions.","abstract_html":"This work deals with the synthesis and reactivity of alpha-trialkylsilyl alpha-amino acids. They were synthesised using an established protocol involving rhodium(II)-catalysed insertion reactions of alpha-trialkylsilyl alpha-diazo esters into N-H bonds of carbamates. As an extension to this procedure, it was accounted that a diastereoselective approach to N-protected alpha-trialkylsilyl alpha-amino acids precursors may lead, after deprotection, to the formation of enantiomerically-pure alpha-trialkylsilyl alpha-amino acids. A variety of diastereoselective synthetic strategies were examinated. These investigations involved the use of alpha-trialkylsilyl alpha-keto-acetates as substrates, as well as various reactants such as chiral amines, ureas, or carbamates as sources of the chiral information. Carbamates were confirmed as the mostly efficient N-H sources for rhodium(II)-catalysed reaction. A diastereoselective N-H insertion reaction was attempted between a alpha-triethylsilyl alpha-diazo benzyl acetate and L-menthyl carbamate. The reaction proceeded in a diastereoselective formation of the N-H inserted product in a diastereomeric ratio of 75 to 25. A part of this project was then devoted to the synthesis of the racemic N-Cbz-protected 2-trimethylsilyl glycine. The possibility to obtain the free carboxylic functional group of the named compound from selective deprotection of a corresponding ester moiety was investigated. Various ester protecting groups were considered, the removal of which could give access to the free carboxylic acids and thus to enantiopure alpha-silyl alpha-amino acids through resolution by chemical methods. The most promising result was obtained when the 2-triethylsilyl-2-diazo-(4-methoxybenzyl) acetate underwent reaction with aluminum thrichloride/ethanthiol to yield to the mono-deprotected compound in a 1H NMR ratio 1.6 to 1 respect to the substrate. Attempts to selective removal of the benzyl ester moiety of N-Cbz-protected alpha-silyl alpha-amino benzyl acetate through selective hydrogenation remained unsuccessful. Hydrogenation over palladium(0) allowed exclusively the formation of the bi-deprotected alpha-silyl alpha-amino acetic acid. The alpha-silyl alpha-amino acid core could become a substructure of a more complicated structure, as for example of a modified Matrix metalloproteinase (MMP) inhibitor. Various synthetic strategies were considered and attempted towards the synthesis of the two building blocks of a silyl modified succinyl hydroxamic acid based MMPs inhibitor. The coupling of a iso-butyl succinyl hydroxamic acid (or the corresponding iso-propyl analogue) and the trifluoroacetic salt of 2-triethylsilyl-2-amino benzyl acetate using various coupling reagents, between them, PyBOP(R) combined with ethyldiisopropylamine, appeared the most promising. Finally, studies on microwave assisted synthesis of N-protected alpha-trialkylsilyl alpha-amino esters were described. A final summary of the several examples reported indicated a shortening of the reaction times under microwave irradiation in comparison to the same transformations performed under standard conditions and conventional heating. To these results, although, did not correspond a sensible enhancement of the chemo- and the stereoselectivity of the discussed reactions.","abstract_has_math":false,"creators":["Veri, Elisabetta"],"institution":"Publikationsserver der RWTH Aachen University","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Bolm, Carsten"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2006,"date_issued":"2006","date_published":"2006","updated_at":"2026-07-30T19:43:10Z","subjects":["info:eu-repo/classification/ddc/540","Chemie","Aminosäuren","Carbene","Rhodium-katalyse","NH Insertion","Amino Acids","Rhodium-catalysis"],"languages":["eng"],"rights":["info:eu-repo/semantics/openAccess"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-123191%22"],"render_values":[{"text":"https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-123191%22","href":"https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-123191%22","code":true}]}]},"links":{"outbound_url":"https://publications.rwth-aachen.de/record/61534","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Bolm, Carsten"]},{"key":"dc:creator","label":"Author","values":["Veri, Elisabetta"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:coverage","label":"Dc Coverage","values":["DE"]},{"key":"dc:date","label":"Dc Date","values":["2006"]},{"key":"dc:publisher","label":"Institution","values":["Publikationsserver der RWTH Aachen University"]},{"key":"dc:relation","label":"Dc Relation","values":["info:eu-repo/semantics/altIdentifier/urn/urn:nbn:de:hbz:82-opus-16924"]},{"key":"dc:type","label":"Dc Type","values":["info:eu-repo/semantics/doctoralThesis","info:eu-repo/semantics/publishedVersion"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["info:eu-repo/classification/ddc/540","Chemie","Aminosäuren","Carbene","Rhodium-katalyse","NH Insertion","Amino Acids","Rhodium-catalysis"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["info:eu-repo/semantics/openAccess"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://publications.rwth-aachen.de/record/61534","https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-123191%22"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["This work deals with the synthesis and reactivity of alpha-trialkylsilyl alpha-amino acids. They were synthesised using an established protocol involving rhodium(II)-catalysed insertion reactions of alpha-trialkylsilyl alpha-diazo esters into N-H bonds of carbamates. As an extension to this procedure, it was accounted that a diastereoselective approach to N-protected alpha-trialkylsilyl alpha-amino acids precursors may lead, after deprotection, to the formation of enantiomerically-pure alpha-trialkylsilyl alpha-amino acids. A variety of diastereoselective synthetic strategies were examinated. These investigations involved the use of alpha-trialkylsilyl alpha-keto-acetates as substrates, as well as various reactants such as chiral amines, ureas, or carbamates as sources of the chiral information. Carbamates were confirmed as the mostly efficient N-H sources for rhodium(II)-catalysed reaction. A diastereoselective N-H insertion reaction was attempted between a alpha-triethylsilyl alpha-diazo benzyl acetate and L-menthyl carbamate. The reaction proceeded in a diastereoselective formation of the N-H inserted product in a diastereomeric ratio of 75 to 25. A part of this project was then devoted to the synthesis of the racemic N-Cbz-protected 2-trimethylsilyl glycine. The possibility to obtain the free carboxylic functional group of the named compound from selective deprotection of a corresponding ester moiety was investigated. Various ester protecting groups were considered, the removal of which could give access to the free carboxylic acids and thus to enantiopure alpha-silyl alpha-amino acids through resolution by chemical methods. The most promising result was obtained when the 2-triethylsilyl-2-diazo-(4-methoxybenzyl) acetate underwent reaction with aluminum thrichloride/ethanthiol to yield to the mono-deprotected compound in a 1H NMR ratio 1.6 to 1 respect to the substrate. Attempts to selective removal of the benzyl ester moiety of N-Cbz-protected alpha-silyl alpha-amino benzyl acetate through selective hydrogenation remained unsuccessful. Hydrogenation over palladium(0) allowed exclusively the formation of the bi-deprotected alpha-silyl alpha-amino acetic acid. The alpha-silyl alpha-amino acid core could become a substructure of a more complicated structure, as for example of a modified Matrix metalloproteinase (MMP) inhibitor. Various synthetic strategies were considered and attempted towards the synthesis of the two building blocks of a silyl modified succinyl hydroxamic acid based MMPs inhibitor. The coupling of a iso-butyl succinyl hydroxamic acid (or the corresponding iso-propyl analogue) and the trifluoroacetic salt of 2-triethylsilyl-2-amino benzyl acetate using various coupling reagents, between them, PyBOP(R) combined with ethyldiisopropylamine, appeared the most promising. Finally, studies on microwave assisted synthesis of N-protected alpha-trialkylsilyl alpha-amino esters were described. A final summary of the several examples reported indicated a shortening of the reaction times under microwave irradiation in comparison to the same transformations performed under standard conditions and conventional heating. To these results, although, did not correspond a sensible enhancement of the chemo- and the stereoselectivity of the discussed reactions."]},{"key":"dc:source","label":"Dc Source","values":["Aachen : Publikationsserver der RWTH Aachen University 155 S. (2006). = Aachen, Techn. Hochsch., Diss., 2006"]},{"key":"dc:title","label":"Title","values":["Synthesis and reactivity of alpha-trialkylsilyl alpha-amino acids"]}]}],"canonical_facts":{"dc:contributor":["Bolm, Carsten"],"dc:coverage":["DE"],"dc:creator":["Veri, Elisabetta"],"dc:date":["2006"],"dc:description":["This work deals with the synthesis and reactivity of alpha-trialkylsilyl alpha-amino acids. They were synthesised using an established protocol involving rhodium(II)-catalysed insertion reactions of alpha-trialkylsilyl alpha-diazo esters into N-H bonds of carbamates. As an extension to this procedure, it was accounted that a diastereoselective approach to N-protected alpha-trialkylsilyl alpha-amino acids precursors may lead, after deprotection, to the formation of enantiomerically-pure alpha-trialkylsilyl alpha-amino acids. A variety of diastereoselective synthetic strategies were examinated. These investigations involved the use of alpha-trialkylsilyl alpha-keto-acetates as substrates, as well as various reactants such as chiral amines, ureas, or carbamates as sources of the chiral information. Carbamates were confirmed as the mostly efficient N-H sources for rhodium(II)-catalysed reaction. A diastereoselective N-H insertion reaction was attempted between a alpha-triethylsilyl alpha-diazo benzyl acetate and L-menthyl carbamate. The reaction proceeded in a diastereoselective formation of the N-H inserted product in a diastereomeric ratio of 75 to 25. A part of this project was then devoted to the synthesis of the racemic N-Cbz-protected 2-trimethylsilyl glycine. The possibility to obtain the free carboxylic functional group of the named compound from selective deprotection of a corresponding ester moiety was investigated. Various ester protecting groups were considered, the removal of which could give access to the free carboxylic acids and thus to enantiopure alpha-silyl alpha-amino acids through resolution by chemical methods. The most promising result was obtained when the 2-triethylsilyl-2-diazo-(4-methoxybenzyl) acetate underwent reaction with aluminum thrichloride/ethanthiol to yield to the mono-deprotected compound in a 1H NMR ratio 1.6 to 1 respect to the substrate. Attempts to selective removal of the benzyl ester moiety of N-Cbz-protected alpha-silyl alpha-amino benzyl acetate through selective hydrogenation remained unsuccessful. Hydrogenation over palladium(0) allowed exclusively the formation of the bi-deprotected alpha-silyl alpha-amino acetic acid. The alpha-silyl alpha-amino acid core could become a substructure of a more complicated structure, as for example of a modified Matrix metalloproteinase (MMP) inhibitor. Various synthetic strategies were considered and attempted towards the synthesis of the two building blocks of a silyl modified succinyl hydroxamic acid based MMPs inhibitor. The coupling of a iso-butyl succinyl hydroxamic acid (or the corresponding iso-propyl analogue) and the trifluoroacetic salt of 2-triethylsilyl-2-amino benzyl acetate using various coupling reagents, between them, PyBOP(R) combined with ethyldiisopropylamine, appeared the most promising. Finally, studies on microwave assisted synthesis of N-protected alpha-trialkylsilyl alpha-amino esters were described. A final summary of the several examples reported indicated a shortening of the reaction times under microwave irradiation in comparison to the same transformations performed under standard conditions and conventional heating. To these results, although, did not correspond a sensible enhancement of the chemo- and the stereoselectivity of the discussed reactions."],"dc:identifier":["https://publications.rwth-aachen.de/record/61534","https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-123191%22"],"dc:language":["eng"],"dc:publisher":["Publikationsserver der RWTH Aachen University"],"dc:relation":["info:eu-repo/semantics/altIdentifier/urn/urn:nbn:de:hbz:82-opus-16924"],"dc:rights":["info:eu-repo/semantics/openAccess"],"dc:source":["Aachen : Publikationsserver der RWTH Aachen University 155 S. (2006). = Aachen, Techn. Hochsch., Diss., 2006"],"dc:subject":["info:eu-repo/classification/ddc/540","Chemie","Aminosäuren","Carbene","Rhodium-katalyse","NH Insertion","Amino Acids","Rhodium-catalysis"],"dc:title":["Synthesis and reactivity of alpha-trialkylsilyl alpha-amino acids"],"dc:type":["info:eu-repo/semantics/doctoralThesis","info:eu-repo/semantics/publishedVersion"]},"updated_at":"2026-07-30T19:43:10Z"}