Transition-Metal Catalyzed Synthesis of Small- and Medium-Sized Rings Applications toward oxazole synthesis, cycloheptadienes, and natural products

Henrik von Wachenfeldt

Research output: ThesisDoctoral Thesis (compilation)

Abstract

This thesis deals with the development of novel methodologies for the synthesis of hetero- and carbocycles enabled by transition metal catalysis.
The second chapter of the thesis describes a gold-catalyzed three-component reaction to form a variety of substituted oxazoles from readily available N-benzylimines, terminal alkynes, and acyl chlorides. Sacrificial benzyl groups are used to merge two otherwise incompatible reactions: acetylide addition to acyl-iminium and cyclization of propargylamides to oxazoles. The mechanism of the reaction is studied by chemical observations and DFT-calculations. Conclusions made from the mechanistic studies were used to develop a non-catalyzed version of the reaction where N-benzyl propargylamines are reacted with acyl chlorides to form oxazoles in up to quantitative yields. Furthermore, this work has also led to the development of novel decarboxylation and 1,2-rearrangements with oxazoles as migrating group and a convenient method to access highly sensitive formylsilanes.
In the third chapter, cationic iridium is used to catalyze the intramolecular 5+2 cycloaddition between vinyl-cyclopropanes and alkynes to form cycloheptadienes. The different reactivity of iridium compared to previously used transition-metals also led to the discovery of an efficient β-hydride elimination to form 1,4-diene and an iridium catalyzed cyclopropanation.
The fourth chapter describes efforts towards a recently discovered propellane natural product that is a possible lead compound in the battle against diabetes. An eight step synthesis of a late intermediate, containing all of the heavy atoms and the stereocenters with correct relative stereochemistry, is presented. The synthesis is initiated by a novel ruthenium-mediated Pauson-Khand reaction between an electron deficient alkyne and an ethylene-equivalent to introduce ten of the twenty-one heavy atoms of the target molecule.
Original languageEnglish
QualificationDoctor
Awarding Institution
  • Centre for Analysis and Synthesis
Supervisors/Advisors
  • Strand, Daniel, Supervisor
Award date2015 May 28
Publisher
ISBN (Print)978-91-7422-396-5
Publication statusPublished - 2015

Bibliographical note

Defence details

Date: 2015-05-28
Time: 13:00
Place: Kemicentrum, Lecture hall B

External reviewer(s)

Name: Hashmi, A. Stephen K.
Title: Professor
Affiliation: Heidelberg University

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Subject classification (UKÄ)

  • Chemical Sciences

Free keywords

  • catalysis
  • transition metal
  • cyclization
  • cycloaddition
  • natural product

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