Asymmetrische Synthese 3-substituierter 4-Methylenproline und Untersuchungen zur Metathese mit vinylischen Sulfoximinen

In the first part an enantio- and diastereselective synthesis of 3-substituted 4-methylene prolines was developed. (S)-N,S-dimethyl-S-phenylsulfoximine was tansformed via an addition, elimination, isomerization route (AEI-route) into the corresponding mixture of E and Z allylic sulfoximines. This conversion yields in all cases more than 85% of the mixture. The ratio between the two isomers ranges from 51/49 to 82/18 depending on the rest R (alkyl, aryl or alkoxy substituent). After separation of the two isomers the (E) allylic sulfoximine was transformed in a titanium mediated aminoalkylation reaction with ethyl N-2-methylpropane-2-sulfonylimino acetate into the two diastereomeric amino acid esters. The two new stereocenters were formed with more than 98% d.e. Only the double bond is formed in a mixture of (E) and (Z). The yield ranges from 58 to 74%. After activation of the two diastereomeric amino acid esters with trimethyloxoniumtetrafluoroborate the intermediate aminosulfoxonium salt were cyclized with KF or DBU to the same 3-substituted 4-methylene prolin in yields between 54 and 78%. The sulfinamide splitted off was isolated in yields greater than 81% and with an enantiomeric excess of 99%. This sulfinamide may be converted to enantiomerically pure (S)-N,S-dimethyl-S-phenylsulfoximine. The deprotection of one of the proline derivatives (R = isopropyl) was successful with diluted trifluoromethane sulfonic acid. The yield was 76%. Further transformations at the double bond (for example hydroboration or dihydroxylation) opens the natural class of the kainoids. Therefore the alkoxy-substituted 4-methylenproline is needed. Oxidation of the alcohol should give the second carboxylic acid, which is common for all kainoids.In the second part there were investigations towards the cross metathesis or ring closing metathesis of vinylic sulfoximines. The synthesis of (S)-vinylic sulfoximine starting from (S)-N,S-dimethyl-S-phenylsulfoximine succeeded only after activation with a phosphoric acid ester and only in 15% yield. This vinylic sulfoximine did not react in cross metathesis reaction. Two other vinylic sulfoximines with a second, endstanding double bond were synthesized. The ring closing metathesis of these two dienes failed despite of different reaction conditions and catalysts. But the results show that a vinylic sulfoximine group is tolerated in metathesis reactions.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2006

Author dc:creator

• Lindenmaier, Andreas

Contributors dc:contributor

• Gais, Hans-Joachim

• info:eu-repo/classification/ddc/540
• Chemie
• Aminosäuren
• Asymmetrische Synthese
• Sulfoximide
• Alkenylsulfoximide
• Prolinderivate
• Aminoalkylierung
• Ringschlussmetathese
• Kreuzmetathese
• Sulfoximine
• alpha-Aminosäuren
• Proline
• asymmetric synthesis
• sulfoximines
• alpha amino acids
• prolines

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-122655%22

OAI identifier oai:identifier

oai:publications.rwth-aachen.de:60970