University of Groningen
Exploring asymmetric catalytic transformations
Guduguntla, Sureshbabu
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Exploring Asymmetric Catalytic Transformations
The work described in this thesis was carried out at the Stratingh Institute
for Chemistry, University of Groningen, The Netherlands.
This work was financially supported by the NWO-CW NSF astrochemistry
program and the University of Groningen.
Printed by Ipskamp Printing BV, Enschede, The Netherlands.
Cover design by Joana Romão and Sureshbabu Guduguntla.
ISBN: 978-94-028-0529-1 (printed version)
Exploring Asymmetric
Catalytic Transformations
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 10 March 2017 at 16.15 hours
by
Sureshbabu Guduguntla
born on 4 June 1988
in Kavalakuntla, India
Supervisor:
Prof. B. L. Feringa
Assessment Committee
Prof. W. R. Browne
Prof. S. R. Harutyunyan
Prof. F. P. J. T. Rutjes
Table of contents
Chapter 1 Introduction 1
1.1 Design of a self-replicating system 3
1.2 Asymmetric autocatalysis and autoinduction 6
1.2.1 Asymmetric autoinduction 6
1.2.2 Asymmetric autocatalysis 8
1.3 Cu-catalyzed asymmetric allylic substitution 11
1.4 Thesis outline 13
1.5 References 14
Chapter 2 Synthesis of optically active β- or γ-alkyl substituted alcohols through copper-catalyzed asymmetric allylic alkylation with organolithium
reagents 21
2.1 Introduction 22
2.2 Results and discussions 23
2.3 Conclusions 29
2.4 Experimental section 29
2.4.1 General procedures 29
2.4.2 General procedure for the one-pot synthesis of β-alkyl substituted alcohols through Cu-catalyzed asymmetric allylic alkylation of allyl bromides with organolithium reagents followed by reductive
ozonolysis 30
2.4.3 General procedure for the synthesis of γ-alkyl substituted alcohols through Cu-catalyzed asymmetric allylic alkylation of allyl bromides with organolithium reagents followed by a
hydroboration/oxidation 37
2.4.4 General procedure for the one-pot synthesis of α-alkyl substituted aldehydes through Cu-catalyzed asymmetric allylic alkylation of allyl bromides with organolithium reagents followed by ozonolysis 41 2.4.5 General procedure for the synthesis of β-alkyl substituted aldehydes through the oxidation of γ-alkyl substituted primary alcohols with
Dess- Martin periodinane 42
2.4.6 General procedure for the synthesis of benzoate ester of the alcohols
2.5 References 43
Chapter 3 Chiral Diarylmethanes via Copper-Catalyzed Asymmetric
Allylic Arylation with Organolithium Compounds 47
3.1 Introduction 48
3.2 Results and discussions 50
3.3 Conclusions 56
3.4 Experimental section 57
3.4.1 General procedure 57
3.4.2 Preparation of allyl bromides 58
3.4.3 Procedure for the synthesis of chiral imidazolium salts 59 3.4.4 General procedure for the preparation of ArLi using lithium metal 64 3.4.5 Genral procedure for the preparation of ArLi using n-BuLi 64 3.4.6 General procedure for the copper-catalyzed asymmetric allylic arylation with organolithium reagents 65 3.4.7 General procedure for the hydroboration-oxidation of the
corresponding alkenes 65
3.4.8 Characterization and analysis of the molecules 66
3.5 References 88
Chapter 4 Enantioselective synthesis of di- and tri- arylated all-carbon quaternary stereocenters via copper catalyzed allylic arylations with
organolithium compounds 91
4.1 Introduction 92
4.2 Results and discussions 94
4.3 Conclusions 99
4.4 Experimental section 100
4.4.1 General procedures 100
4.4.2 GC-MS conditions 101
4.4.3 General procedure for the synthesis of (E)-allyl bromides 102 4.4.4 Procedure for the synthesis of (+)-CuClL16 106
4.4.5 General procedure for the synthesis of copper-catalyzed asymmetric allylic arylation with organolithium reagents 107 4.4.6 General procedure for the hydroboration-oxidation of the
corresponding alkenes 108
4.5 References 121
Chapter 5 Efforts towards the development of a new asymmetric
autocatalytic reaction: nucleophilic addition of dialkyl phosphites to
aldehydes 127
5.1 Introduction 128
5.1.1 Enantioselective synthesis of α-hydroxy phosphonates: nucleophilic addition of dialkyl phosphites to carbonyl compounds 129
5.2 Goal 131
5.3 Results and discussions 132
5.4 Conclusions 141
5.5 Experimental section 141
5.5.1 General procedures 141
5.5.2 Synthesis of (S)-diisopropyl hydroxy(phenyl)methylphosphonate
(9) 142
5.5.3 Synthesis of (R)-dimethyl hydroxy(phenyl)methylphosphonate
(12) 144
5.5.4 General procedure for the synthesis of chiral (racemic) non-
symmetrical dialkyl phosphites 145 5.5.5 General procedure for the entries in Table 1 146
5.5.6 General procedure for the entries 3, 4, 6, 7, 10, 11 and 12 in Table
2 147
5.5.7 General procedure for the entries 1, 2, 5, 8, 9 and 13 in Table
2 147
5.5.8 General procedure: Nucleophilic addition of diisopropyl phosphite 8 to benzaldehyde 7 in the presence of chiral Mg-alkoxide 13 148 5.5.9 General procedure: Nucleophilic addition of diisopropyl phosphite 8 to benzaldehyde 7 in the presence of chiral Li-alkoxide 14 148
5.5.10 General procedure: Nucleophilic addition of diisopropyl phosphite 8 to benzaldehyde 7 in the presence of chiral Al-alkoxide 15 149 5.5.11 General procedure: Nucleophilic addition of ethylmethyl phosphite 24 to benzaldehyde 7 in the presence of chiral Li-alkoxide 28 150
Chapter 6 Efforts towards the development of a new asymmetric
autocatalytic reaction: metal-ligand approach 157
6.1 Introduction 158
6.1.1 Titanium-promoted catalytic enantioselective addition of Grignard
reagents to aldehydes 158
6.1.2 Asymmetric reduction of ketones using CBS-oxazaborolidine 162
6.2 Design 164
6.3 Results and discussion 165
6.4 Conclusions 172
6.5 Experimental section 173
6.5.1 General procedures 173
6.5.2 Synthesis of racemic 1-(hydroxy(phenyl)methyl)naphthalen-2-ol
(14) 174
6.5.3 Synthesis of (S)-1-(hydroxy(phenyl)methyl)naphthalen-2-ol (14) 175 6.5.4 Synthesis of 2-methoxy-1-naphthaldehyde (20) 178 6.5.5 Synthesis of (S)-(2-Methoxynaphthalen-1-yl)(phenyl)methanol
(21) 179
6.5.6 General procedure: nucleophilic addition of PhMgBr to aldehydes in the presence of a chiral ligand 180 6.5.7 Nucleophilic addition of PhMgBr to 2-hydroxy-1-naphthaldehyde 7 in the presence of (S)-14 with 92% ee 181 6.5.8 Nucleophilic addition of PhMgBr to 2-methoxy-1-naphthaldehyde 20 in the presence of (S)-21 with 94% ee (Table 1) 181 6.5.9 Nucleophilic addition of PhMgBr to 2-methoxy-1-naphthaldehyde 20 in the presence of (S)-BINOL 181 6.5.10 Asymmetric reduction of (2-hydroxynaphthalen-1-
yl)(phenyl)methanone 16 in the presence (S)-14 with 10% ee 182
6.5.11 Reduction of ketone 16 with borane 182
6.6 References 183
Chapter 7 Efforts towards the development of new asymmetric
autocatalytic reactions: H-bond donor approach 187
7.1 Introduction 188
7.1.1 Bifunctional urea or thiourea catalyzed Mannich reaction 188 7.1.2 Bifunctional urea or thiourea catalyzed Kabachnik–Fields (phospha-
7.2 Design 193
7.3 Results and discussion 194
7.3.1 Bisurea system 194 7.3.2 Kabachnik–Fields reaction 196 7.4 Conclusions 199 7.5 Experimental section 200 7.5.1 General procedures 200 7.5.2 Synthesis of imine (16) 201 7.5.3 Synthesis of 4-(N,N-dimethylamino)picolinaldehyde (26) 204 7.5.4 Synthesis of 2-((N,N-dimethylamino)methyl)benzaldehyde (27) 204 7.5.5 General procedure for the Mannich reaction 205 7.5.6 General procedure for the three component (Kabachnik–Fields)
reaction 205
7.6 References 206
Samenvatting 211
Summary 217
