Carbene catalyzed asymmetric nucleophilic acylations with novel triazolium salts

Han, Jianwei; Enders, Dieter

doi:urn:nbn:de:hbz:82-opus-26575

Carbene catalyzed asymmetric nucleophilic acylations with novel triazolium salts = Carben-katalysierten asymmetrischen nucleophilen Acylierungen mit neue Triazoliumsalze

Han, Jianwei

2008

Verantwortlichkeitsangabevorgelegt von Jianwei Han

ImpressumAachen : Publikationsserver der RWTH Aachen University 2008

Umfang173 S.

Aachen, Techn. Hochsch., Diss., 2008

Genehmigende Fakultät
Fak01

Hauptberichter/Gutachter
Enders, Dieter (Thesis advisor)

Tag der mündlichen Prüfung/Habilitation
2008-12-08

Online
URN: urn:nbn:de:hbz:82-opus-26575
URL: https://publications.rwth-aachen.de/record/50530/files/Han_Jianwei.pdf

Einrichtungen

Inhaltliche Beschreibung (Schlagwörter)
Stetter-Reaktion (Genormte SW) ; Acylierung (Genormte SW) ; Chemie (frei) ; nucleophile Carbene (frei) ; Triazoliumsalze (frei) ; nucleophilic carbene (frei) ; Stetter reaction (frei) ; Triazolium salts (frei) ; nucleophilic acylation (frei)

Thematische Einordnung (Klassifikation)
DDC: 540

Kurzfassung
Wir haben eine Familie neuer chiralen Triazoliumsalze entwickelt, welche die Benzoin Kondensation mit 8-95% Ausbeute und 21-95% Enantioüberschuß katalysierten. Basierend auf dieser Strategie des Carben-Designs haben wir verschiedene N-substituierte Triazioliumsaze entwickelt, welche die intermolekulare Stetter Reaktion katalysierten. Dadurch wurde 1,4-Diketone in moderater bis exellenter Ausbeute (49-98%) und moderater bis guter Enantioselektivität (56-78%) erhalten, die durch Umkristallisation zum exellenten Niveau (bis 99% ee) erhöht werden konnte. Zusätzlich wurde die N-heterocyclische Carbene katalysierte asymmetrische Addition der heterocyclischen Aldehyde an Arylidenmalonate entwickelt, wodurch chirale Polycarbonylverbindungen mit guter Ausbeute (>85%) und guter Enantioselektivität (bis 78% ee) gebildet wurden. Wichtiger ist, dass exellenter Enantioüberschuß (> 99% ee) einfach durch Umkristallisation erhalten werden konnte. Die Anwendung der intramolekularen Kondensation zur Synthese des Naturstoffs (-)-Eucomol wurde untersucht.

We have developed a practical and efficient synthesis of a family of new chiral trazolium salts from (S)-glutamic acid. With access to the new precarbene catalysts we started to verify their ability to promote the benzoin condensation and intramolecular Stetter reaction. The optimal conditions were identified and allowed for an expansion of the reaction scope with 8-95% yield and enantiomeric excesses of 21-95% in the benzoin condensation. Furthermore, these carbene precatalysts have been applied to intramolecular Stetter reaction with good efficiency and moderate selectivity. Based on the strategy of carbene design, we have developed different N-substituted triazolium salts, which successfully catalyzed the intermolecular Stetter reaction. The structure of 1-Methyl triazolidine was elucidated by X-ray structure analysis. Moreover, we have demonstrated that 1-methyl triazolidine lacked catalytic activity in the intermolecular Stetter reaction. In the processes of searching the optimal carbene generating high enantioselectivities, we prepared a variety of chiral, nucleophilic carbenes which has benefited from the expected impact of the fused ring, N-based substituent and nature of the side chain steric demand. Finally, after screening different conditions, we were able to obtain the 1,4 diketones in moderate to excellent yields (49 98%) and moderate to good enantioselectivities (56 78% ee), which could be enhanced by one recrystallization to excellent levels (90 99% ee). In addition, examination of the reaction course revealed new mechanistic insights about the formation of the Stetter product. We have extended the intermolecular Stetter reaction to a variety of electron rich aldehydes coupled to a variety of Michael acceptors. In this context, we have developed the asymmetric version of the addition of heterocyclic aldehydes to arylidene-malonates catalyzed by N-heterocyclic carbenes, which afforded chiral polycarbonyl compounds in good yields (>85%) and good enantioselectivities (up to 78% ee). More importantly, excellent enantiomeric excesses (up to >99% ee) were obtained after single recrystallization. Furthermore, this method can open a practical entry to develop gram-scale nucleophilic acylation products for polycarbonyl compounds, which could used for synthesizing potential precursors of enzymatic inhibitors.The intramolecular benzoin condensation to synthesize natural products (-)-eucomol have been explored.

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