Asymmetrische Synthese Delta 3a,4 -ungesättigter bicyclischer Prolin-Analoga und Festphasensynthese mit vinylischen Sulfoximinen

In the first part enantiomerically pure acyclic and cyclic allylic sulfoximines were transformed to the corresponding alpha-titanated compounds and reacted with N-tert-butylsulfonyl a-imino ethyl ester to give acyclic and monocyclic protected alpha-amino acid esters in yields of 32-97%. In all cases the alpha-amino acid esters were formed in a highly regio and diastereoselective fashion (>=98% de). The amino alkylation of cyclic allylic sulfoximines with N-tert-butylsulfonyl alpha-imino ethyl ester provided mixtures of E and Z-konfigured monocyclic alpha-amino acid derivatives. Both diastereomers were formed highly diastereoselective (>=98% de). The stereoselective formation of the products could be explained assuming a six-membered transition state model. The four step synthesis of N-tert-butylsulfonyl alpha-imino ethyl ester was optimized so that the overall yield could be raised from 20% to 63%. The E and Z-konfigured monocyclic alpha-amino acid derivatives were treated with Me3OBF4 to give the corresponding 1-alkenyl dimethylamino sulfoxonium salts in excellent yields of 93-96%. The obtained 1-alkenyl dimethylamino sulfoxonium salts were transformed via intramolecular nucleophilic substitution with either DBU or lithium-tert-butyl amide in good yields of 76-81% to D3a,4-unsaturated bicyclic proline analogues. The cyclization reaction starts with a base induced isomerization of the 1-alkenyl dimethylamino sulfoxonium salts to the novel 2-alkenyl dimethylamino sulfoxonium salts. Then the nucleophilic substitution occurs under formation of the unsaturated bicyclic proline derivatives and N,N-dimethylphenylsulfinamide of >=99% ee. The obtained yields were in a range of 74-76%. Finally, cleavage of the protecting group with anhydrous triflic acid furnished the fused bicyclic proline analogue containing an unsaturated six-membered ring in a high yield of 83%. In the second part the attempt to prepare an axial chiral vinylic sulfoximine on Merrifield resin failed because in all steps the conversion of the starting material was not complete. Therefore a mixture of at least four different compounds remained on solid support after three steps and it was impossible to calculate the equivalents of reagents used in the next transformation accurately. At this point the project was stopped. In a second approach (+)-(aS,SS)-(S-(4-tert-butyl-cyclohexylidene methane)-(N-(2-hydroxy ethyl)-S-phenyl sulfoximine was synthesized in solution in 47% and >=98% de. The plan was to heterogenize this compound in enantiomerically pure form on a silyl chloride resin. Four different approaches were tried to fix the compound to solid support but in all cases the loading was only 21-25%. In a control experiment a literature known compound was heterogenized successfully. Because of the low loadings also this project was cancelled.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2004

Author dc:creator

• Koep, Stefan

Contributors dc:contributor

• Gais, Hans-Joachim

• info:eu-repo/classification/ddc/540
• Prolinderivate
• Bicyclische Verbindungen
• Ungesättigte Verbindungen
• Allylgruppe
• Aminoalkylierung
• Synthon
• Chemie
• Asymmetrische Synthese
• Sulfoximine
• bicyclische Aminosäuren
• Festphasensynthese

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-123581%22

OAI identifier oai:identifier

oai:publications.rwth-aachen.de:61979