Derivatisierungsreaktionen von Cinchona-Alkaloiden und eine Cinchona-Alkaloid-katalysierte asymmetrische Synthese von 2,5-Diarylphopholanen

This thesis consists of two parts: The first part deals with the synthesis of structurally diverse cinchona alkaloid derivatives via nucleophilic addition of organometallic reagents. An addition of organolithium reagents leads to 2´-alkylated products. The reaction with Grignard reagents leads to new 4´-substituted cinchona alkaloid derived aminals via conjugate addition. Direct core-alkylation by means of organometallic reagents is an easy way to access structural analogues of the cinchona alkaloids. Several functional groups of the alkaloid do not partake in this reaction and thus remain within the reaction products, providing a handle for further functionalization, or suggesting use of those derivatives as organocatalysts or as ligands for transition metals. The second part of this thesis describes an asymmetric catalytic total synthesis of (2R,5R)-diphenylphospholanic acid (Fiaud’s acid; 1-hydroxy-1r-oxo-2c,5t-diphenylphospholane). We have developed a nickel-catalyzed cross-coupling reaction of thiophene with aryl Grignard reagents to form (E,E)-1,4-diarylbutadienes. Trialkylphosphines as well as N-heterocyclic carbenes serve as ligands for nickel. Under these conditions we were able to synthesize various diarylbutadienes in yields of up to 75%. Submitted to a McCormack cycloaddition reaction, these butadienes reacted to give meso-2,5-diarylphosphol-3-enamides. The yield of the phosphacycles varied between 24 and 84%, depending on the steric hinderance of the aryl substituent. An organocatalytic asymmetric desymmetrization of the meso-phospholenes with cinchona alkaloids acting as bifunctional catalysts in acetonitrile solution gave the corresponding 2-phospholenes in quantitative yields with an enantiomeric excess of up to 91%. The 2,5-diphenyl-2-phospholeneamide was hydrolyzed to the phospholenic acid in aqueous acid. Diastereoselective reduction of the unsaturated acid with sodium in liquid ammonia and ammonia sulphate as proton source gave the phospholanic acid in quantitative yield in a diastereomeric ratio of trans/cis = 7.7:1. Crystallization from methanol gave the pure trans-diastereomer of Fiaud’s phospholanic acid with an enantiomeric excess of >98%.

Grantor dc:publisher

Publikationsserver der RWTH Aachen University

Year dc:date

2009

Author dc:creator

• Schmitz, Marco

Contributors dc:contributor

• Hintermann, Lukas

• info:eu-repo/classification/ddc/540
• Cinchonaalkaloide
• Phospholane
• Homogene Katalyse
• Asymmetrische Synthese
• Nickel
• Grignard-Reaktion
• Chemie
• cinchona alkaloids
• phospholanes
• homogeneous catalysis
• asymmetric synthesis
• grignard reaction

Statement dc:rights

• info:eu-repo/semantics/openAccess

Language dc:language

ger

Identifier

https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-113531%22

OAI record oai:identifier

https://publications.rwth-aachen.de/oai2d?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Apublications.rwth-aachen.de%3A51219