Yan, Xingchen

English

As a result of decades of research, it is currently possible to perform catalytic asymmetric conjugate additions of organometallics to many classes of Michael acceptors with excellent enantioselectivities and product yields. However, most of these examples comprise relatively reactive and conventional Michael acceptors. Conjugate additions to unconventional less reactive Michael acceptors such α,β-unsaturated carboxamides, α,β-unsaturated carboxylic acids and quinolines which are of major importance in organic synthesis, are still unreachable despite decades of research in this direction. To solve these long standing problems, we have developed a new strategy based on our previous researches. By combining reactive Lewis acids and Grignard reagents, we have tackled their reactivity issues and enabled their asymmetric conjugated addition reactions. Solving these problems allowed us to obtain a series of interesting chiral molecules that can be used for future transformations and applications

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   University of GroningenCopper-catalyzed enantioselective conjugate addition of Grignard reagent to non-activatedacceptorsYan, XingchenIMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2019Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Yan, X. (2019). Copper-catalyzed enantioselective conjugate addition of Grignard reagent to non-activatedacceptors. University of Groningen.CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.Download date: 07-06-2022     Copper-catalyzed enantioselective conjugate addition of Grignard reagent to non-activated acceptors enabled by Lewis acid                                                             Xingchen Yan                             The work described in this thesis was carried out at Stratingh Intitute for Chemistry, University of Groningen (The Netherlands) This work was financially supported by Ministry of Education, Culture and Science (Gravitation program 024.001.035), the Netherlands Organization for Scientific Research (NWO) and China Scholarship Council (CSC) Printed by Ridderprint BV, Ridderkerk, The Netherlands ISBN: 978-94-034-1746-2 (Printed Book) ISBN: 978-94-034-1745-5 (Ebook)             Copper-catalyzed enantioselective conjugate addition of Grignard reagent to non-activated acceptors enabled by Lewis acid      PhD thesis     to obtain the degree of PhD at the University of Groningen on the authority of the Rector Magnificus prof. E. Sterken and in accordance with the decision by the College of Deans.  This thesis will be defended in public on   Friday 12 July 2019 at 12.45 hours    by    Xingchen Yan  born on 25 May 1988 in Shandong, China     Supervisors Prof. S. R. Harutyunyan  Prof. W. R. Browne     Assessment committee Prof. M. A. Fernandez Ibanez  Prof. E. Otten  Prof. M. D. Witte             Table of contents 1. Chapter 1: Introduction                                                                                                                       1.1 Catalytic enantioselective conjugate addition of organometallics                        pag. 2 1.2 Catalytic asymmetric conjugate addition of Grignards to α,β-unsaturated ketones                                                                                                                                                           pag. 2 1.3 Catalytic asymmetric conjugate addition of Grignards to α,β-unsaturated esters                                                                                                                                                         pag. 10 1.4 Catalytic asymmetric conjugate addition of Grignards to other Michael acceptors                                                                                                                                                         pag. 15 1.5 Catalytic asymmetric conjugate addition of Grignards enabled by Lewis acid                                                                                                                                                         pag. 16 1.6 Outline of this thesis                                                                                                         pag. 20 1.7 References                                                                                                                           pag. 22  2. Chapter 2: Lewis acid enabled copper-catalyzed asymmetric synthesis of chiral β-substituted amides 2.1 Introduction                                                                                                                        pag. 26 2.2 Results and discussions                                                                                                   pag. 27  2.3 Conclusions                                                                                                                          pag. 34 2.4 Experimental section                                                                                                        pag. 35 2.5 References                                                                                                                           pag. 63  3. Chapter 3: Mechanistic studies on Lewis acid enabled copper-catalyzed enantioselective conjugate addition of Grignards to α,β-unsaturated carboxamides 3.1 Introduction                                                                                                                        pag. 68 3.2 Results and discussions                                                                                                   pag. 70  3.3 Conclusions                                                                                                                          pag. 95 3.4 Experimental section                                                                                                        pag. 95     3.5 References                                                                                                                         pag. 102  4. Chapter 4: Copper-catalyzed enantioselective direct conjugate addition of Grignard reagents to α,β-unsaturated carboxylic acids enabled by Lewis acid 4.1 Introduction                                                                                                                      pag. 104 4.2 Results and discussions                                                                                                 pag. 105  4.3 Conclusions                                                                                                                       pag. 114 4.4 Experimental section                                                                                                     pag. 115 4.5 References                                                                                                                         pag. 145  5. Chapter 5: Lewis acid enabled copper-catalyzed enantioselective conjugate addition of Grignards to quinolines 5.1 Introduction                                                                                                                      pag. 150 5.2 Results and discussions                                                                                                 pag. 153  5.3 Conclusions                                                                                                                       pag. 162 5.4 Experimental section                                                                                                     pag. 163 5.5 References                                                                                                                         pag. 165  6. Summary English summary                                                                                                                    pag. 167 Nederlandse samenvatting                                                                                                 pag. 169   7. List of abbreviations                                                                                                                    pag. 173  8. Acknowledgements                                                                                                                     pag. 175        

Copper-catalyzed enantioselective conjugate addition of Grignard reagent to non-activated acceptors

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Copper-catalyzed enantioselective conjugate addition of Grignard reagent to non-activated acceptors

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