Mechanistic Investigation, Development and Synthetic Applications of a Catalytic Enantioselective and Diastereoselective Allylboration Methodology

  • Author / Creator
    Rauniyar, Vivek
  • Over the past two decades and continuing on, carbonyl allylation chemistry has been a very useful and popular tool for the stereocontrolled formation of carbon-carbon bonds in the field of organic synthesis. In the context of natural product synthesis, the efficiency and status of aldehyde allylboration method is only matched by the asymmetric and diastereoselective aldol methodology. Unfortunately, prior to the new millennium, the means to control the absolute stereoselectivity in the addition of allylic boron reagents had been restricted to stoichiometric chiral directors, appended onto the metal center. In 2002, the research groups of Hall and Miyaura reported a new Lewis acid-catalyzed allylboration reaction manifold, which raised intriguing mechanistic questions and also paved the way for a catalytic enantioselective methodology development. Chapter 2 of this thesis details mechanistic studies related to the new Lewis acid-catalyzed allylboration. In this chapter, various control experiments and kinetic studies are presented, the results of which allowed us to propose a hypothesis involving the electrophilic boronate activation as the key factor for the observed rate enhancement. Chapter 3 describes the initial phase of our research to develop a catalytic enantioselective allylboration methodology. We discovered that Brønsted acid catalysts derived from diol•SnCl4 complexes were promising catalysts for the asymmetric addition of air and moisture stable and commercially available allylic pinacol boronates. Under this 1st generation catalyst-system, the corresponding homoallylic alcohols were obtained in moderate to good enantioselectivity and excellent diastereoselectivity. The development of a novel chiral Brønsted acid catalyst for the highly enantio- and diastereoselective allylboration reaction methodology is the single most important result to come from this thesis. Chapter 4 outlines the development of the 2nd generation catalyst system. A systematic study of the diol component of the catalyst system led us to arrive at a novel diol nicknamed Vivol on behalf of my contribution. The resulting Brønsted acid derived from Vivol•SnCl4 now provided the corresponding homoallylic alcohol products in very good to excellent enantioselectivity. Preliminary mechanistic studies along with the X-ray diffraction structure of the catalyst system are also presented. Based on this information, an even better performaning diol (termed F-Vivol) was developed. This 3rd generation catalyst system derived from F-Vivol•SnCl4 complex was shown to display consistently superior reactivity and selectivity over its 2nd generation predecessor. Chapter 5 describes our efforts to expand the reagent scope of the Brønsted acid catalyzed allylboration methodology. Furthermore, this chapter also describes the successful application of the catalytic process towards the synthesis of simple and complex molecules. Accordingly, the preparation and application of the Brønsted acid-catalyzed addition of 2-bromoallyl boron pinacolate is described. The successful transformation of the corresponding bromo-homoallylic alcohols to a compelling class of γ-butyrolactones is also presented. The later part of the Chapter presents the synthesis of natural products (+) dodoneine and palmerolide A.

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  • Degree
    Doctor of Philosophy
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    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
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    University of Alberta
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  • Supervisor / co-supervisor and their department(s)
  • Examining committee members and their departments
    • Frederick G. West, Department of Chemistry, Jeffrey M. Stryker, Department of Chemistry, Steven H. Bergens, Department of Chemistry, Kamaljit Kaur, Faculty of Pharmacy and Pharmaceutical Sciences, William D. Wulff, Department of Chemistry, Michigan State University