University of Groningen
Copper-catalyzed enantioselective conjugate addition of Grignard reagent to non-activated acceptors
Yan, Xingchen
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Publication date: 2019
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Yan, X. (2019). Copper-catalyzed enantioselective conjugate addition of Grignard reagent to non-activated acceptors. University of Groningen.
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Copper-catalyzed enantioselective conjugate addition of
Grignard reagent to non-activated acceptors enabled by
Lewis acid
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)
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
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
