Novel sulfur containing electrophiles in asymmetric organocatalysis

Hoffman, Krzysztof; Enders, Dieter

doi:2853

Novel sulfur containing electrophiles in asymmetric organocatalysis = Schwefel-Elektrophile in der Asymmetrische Organokatalyse

Hoffman, Krzysztof (Author)

2008

Verantwortlichkeitsangabevorgelegt von Krzysztof Hoffman

ImpressumAachen : Publikationsserver der RWTH Aachen University 2008

UmfangII, 128 S.

Aachen, Techn. Hochsch., Diss., 2008

Genehmigende Fakultät
Fak01

Hauptberichter/Gutachter
Enders, Dieter (Thesis advisor)

Tag der mündlichen Prüfung/Habilitation
2008-10-13

Online
URN: urn:nbn:de:hbz:82-opus-28535
URL: https://publications.rwth-aachen.de/record/51123/files/Hoffman_Krzysztof.pdf

Einrichtungen

Fachgruppe Chemie (150000)

Inhaltliche Beschreibung (Schlagwörter)
Organokatalyse (Genormte SW) ; Sulfonate (Genormte SW) ; Chemische Synthese (Genormte SW) ; Asymmetrische Synthese (Genormte SW) ; Biomimetische Synthese (Genormte SW) ; Chemie (frei) ; asymmetric (frei) ; organocatalysis (frei) ; sulfonates (frei) ; hydrogenbonding (frei)

Thematische Einordnung (Klassifikation)
DDC: 540

Kurzfassung
Ziel dieser Arbeit war die Untersuchung von drei Typen von Schwefel-Elektrophilen in verschiedenen metall- und organokatalysierten Reaktionen. Die erste diasteroselektive Reaktion von beta-Ketoestern mit 1-Chloromethylphenylsulfiden katalysiert von Cinchona-Alkaloiden wurde gezeigt. Gleichzeitig, sehr hohe Substratspezifität in Reaktionen mit alpha-Chlorosulfiden wurde bestätigt. Diese Arbeit zeigt dass enanantioselektive und diastereoselektive Reaktionen mit alpha-Chlorosulfiden möglich sind, wobei zwei gleichzeitig wirkende Katalysatoren am Reaktionsmechanismus beteiligt sind. Auch erste Phenylthiometylierung von Aldehyden und Ketonen wurde augewertet. Leider, war es nicht möglich, diesen Prozess enantioselektiv durchzuführen. Davon abgesehen kann die untersuchte Reaktion aber als Methode für indirekte Methylierung von Carbonylverbindungen dienen welche auch mit säurelabilen Substraten funktioniert. Darüber hinaus, wurden alpha,beta-ungesättigte Sulfonate als Elektrophile in verschiedenen metall- und organokatalysierten Reaktionen untersucht. Erste Sulfa-Michael-Additionen von aromatischen Thiolen an (E)-Sulfonate wurden gezeigt. Die Produkte wurden in guten bis sehr guten Ausbeuten und mit Enantiomerenüberschussen von bis zu 64% erhalten. Diese Studien zeigen auch das erste Beispiel für Wasserstoffbrückenbindung zwischen der Sulfonatgruppe und einer chiralen Säure in Übergangszustand.

Three different kinds of sulfur containing electrophiles in organo- and metal catalyzed reactions have been evaluated. We demonstrated the first diastereoselective reaction of beta-keto esters with 1-chloroethylphenyl sulfide catalyzed by cinchona alkaloids. At the same time, we could confirm the high substrate specificity of the reactions with alpha-chlorosulfides. The conditions optimized for methyl-2-cyclopentanonecarboxylate allowed us to perform reactions only with the very similar 2-acetylbutyrolactone. It has been shown that diastereo- and enantioselective reactions with this class of electrophiles are possible. They involve a dual catalytic cycle. In both cases moderate to very good yields and diastereoselectivities were obtained. However, the design of a general method for wide substrate scope was unsuccessful. Due to their liability, alpha-chlorosulfides are problematic electrophiles for use in Lewis acid- and organocatalyzed reactions. We also demonstrated the first catalytic phenylthiometylation of ketones and aldehydes. Unfortunately, it was impossible to perform this process with any enantioselectivity. However, this method can be used for indirect methylation of carbonyls and works well with acid-sensitive compounds such as dioxanone. We also evaluated the reactivity of various phenylthiomethyl amines towards protonation. We claim that aromatic are a stable class of compounds, which do not undergo acid-catalyzed cleavage of free amine to furnish a reactive carbocation. Lastly, we investigated the reactivity of alpha,beta-unsaturated sulfonates in many metal- and organocatalyzed reactions. We evaluated their reactivity and assembled a general procedure for the sulfa-Michael addition of aromatic thiols to (E)-sulfonates. However, this group of compounds turned out to be not very reactive and little similarities to nitroolefins can be postulated. We were able to obtain SMA-products with generally good yields and with enantiomeric excesses up to 64%. We observed that with the increase of enantioselectivity the reaction rate decreased. We also observed that more sterically hindered acceptors gave lower enantiomeric excess. The studies here represent the first activation of sulfonates via hydrogen bond formation with chiral thioureas. We also demonstrated that bifunctional catalysts are the catalysts of choice for many organocatalyzed processes. Furthermore, the reactivity of alpha,beta-unsaturated sulfonates in various reactions has been evaluated. It has been shown that organocatalyzed reactions with carbon nucleophiles (enamine-catalyzed Michael addition, addition of malonates) were impossible to perform. Moreover, our efforts to perform MBH-reactions with benzaldeyde or Henry reactions with different nitro compounds were unsuccessful. In general, alpha,beta-unsaturated sulfonates were not reactive under various reactions conditions with different catalytic systems.

Fulltext:
PDF