Synthesis and exploration of chiral aza-bis(oxazolines) and organocatalysts in asymmetric reactions [Elektronische Ressource] / vorgelegt von Ramesh Rasappan

Ramesh

Informations

• Publié par: universitat_regensburg
• Publié le: 01 janvier 2009
• Nombre de lectures: 9
• Langue: English
• Poids de l'ouvrage: 27 Mo

Extrait

Synthesis and exploration of chiral aza-bis(oxazolines)
and organocatalysts in asymmetric reactions




Dissertation!


des Doktorgrades der Naturwissenschaften (Dr. rer. nat.)
der Naturwissenschaftlichen Fakultät IV - Chemie und Pharmazie
der Universität Regensburg!



!
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vorgelegt von

Ramesh Rasappan





Aus
Pandamangalam (Indien)

Regensburg - 2009













Diese Arbeit wurde angeleitet von Prof. Dr. O. Reiser
Promotionsgesuch eingereicht am: 9 Februar, 2009
Tag der mündlichen Prüfung: 17 März, 2009

Prüfungsausschluß: Prof. Dr. S. Elz (Vorsitzender)
Prof. Dr. O. Reiser (1. Gutachter)
Prof. Dr. F. E. Kühn (2. Gutachter)
Prof. Dr. B. König (3. Prüfer)


Die vorliegende Arbeit wurde unter der Leitung von Herrn Prof. Dr. O. Reiser in der Zeit
von Oktober 2005 bis März 2009 am Institut für Organische Chemie der Universität
Regensburg angefertigt.
















Herrn Prof. Dr. O. Reiser möchte ich für die Überlassung des äußerst interessanten Themas,
die anregenden Diskussionen und stete Unterstützung während der Durchführung dieser
Arbeit danken. !
!
!
!
!
!
!
!
!
for my Parents
& sister
"The setting sun
asked who will
light this
world after me"
"A little lamp
said I WILL
DO MY
PART" !"#$%&'(&)'*+%*+, &
&
1 Introduction
1.1 Catalysis 1
1.2 Historical development 1
1.3 Landmarks in asymmetric catalysis 6
1.4 New generation of catalyst design 10
1.5 Conclusion 12
2 Aim of the work
2.1 Secondary activation of azabox-MX complex 15 n
2.2 Immobilization of azabox on fluorous supports and dendrimers 17
3 Synthesis and immobilization of aza-bis(oxazolines)
3.1 Synthesis of aza-bis(oxazolines) 20
3.2 Immobilization of aza-bis(oxazolines) 21
4 Michael addition of indoles to benzylidene malonates
4.1 Bis(oxazolines) mediated asymmetric Friedel-Crafts alkylations 25
4.2 Tris-(oxazoline) ligands 25
4.3 Aza-bis(oxazolines) 26
4.4 Importance of ligand/metal ratio 27
4.5 Conclusion 30
5 Immobilization of aza-bis(oxazoline) on fluorous supports
5.1 Introduction 34
5.2 Immobilization of azabox on fluorous supports 35
5.3 Kinetic resolution of (±)-hydrobenzoin 36
5.4 Henry (Nitro Aldol) reaction 38
5.5 Palladium mediated allylation 40
5.6 Michael addition of indoles to benzylidene malonates 41
5.7 Conclusion 41
6 Secondary activation of azabox-MX Complex n
6.1 Introduction 44
6.2 Kinetic resolution of (±)-1,2-diols 45
6.3 Boron trifluoride as a secondary Lewis acid 46 !"#$%&'(&)'*+%*+, &
&
6.4 Enantioselective Friedel-Crafts alkylation of indoles 48
6.5 Diels-Alder reaction 50
6.6 Conclusion 51
7 Kinetic resolution of sulfinamide and sulfinyl imines
7.1 Introduction 53
7.2 Kinetic resolution of sulfinamide 53
7.3 Kinetic resolution of sulfinimines 54
7.4 Conclusion 56
8 Copper(II) mediated C!C coupling reaction
8.1 Introduction 58
8.2 In(III) and Yb(III) mediated coupling reaction 59
8.3 Fe(III), Cu(II) and Sc(III) mediated direct coupling 60
8.4 Allylic alcohols as an electrophile 61
8.5 Benzylic acetate as an effective electrophile 63
8.6 Coupling of allylic acetate and !-ketoesters 65
8.7 Pd(II) and Cu(II) combined allylations 67
8.8 Conclusion 68
9 Hydroamination and aminohalogenation
9.1 Introduction 70
9.2 Cu(II) and Fe(III) mediated hydroamination 70
9.3 Hydroamination at room temperature 73
9.4 Asymmetric haloamination 74
9.5 Conclusion 79
10 Organocatalysis
10.1 Introduction 80
10.2 Historical background 80
10.3 Primary amine organocatalyst 84
10.4 New catalyst design 86
10.5 Synthesis of cyclohexadiamine derived organocatalysts 86
10.6 Cyclohexadiamine organocatalyst mediated aldol reactions 87 !"#$%&'(&)'*+%*+, &
&
10.7 Michael additions of ketones to nitro olefins 88
10.8 Role of additives in pyrrole formation 92
10.9 Conclusion 93
11 Summary
11.1 Michael addition of indoles to benzylidene malonates 96
11.2 Immobilization of aza-bis(oxazolines) on fluorous supports 97
11.3 Organocatalysis 100
12 Experimental part
12.1 General information 102
12.2 Synthesis of aza-bis(oxazolines) 104
12.3 Michael addition of indoles to benzylidene malonates 108
12.4 Immobilization of aza-bis(oxazoline) on fluorous tag 112
12.5 Secondary activation of azabox-MX Complex 118 n
12.6 Kinetic resolution of sulfinamide and sulfinyl imines 119
12.7 Copper(II) mediated C!C coupling reaction 122
12.8 Hydroamination and aminohalogenation 125
12.9 Organocatalysis 130
13 Appendix
1 1313.1 H and C NMR spectra 141
13.2 HPLC spectra 193
14 Acknowledgement 200
15 Curriculum vitae 202 Abbreviations
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Abbreviations

Me methyl
Abs absolute
MeCN acetonitrile
AIBN azo-isobutyronitrile
Mes mesyl
BOC tert-butoxycarbonyl
min minute
Bn benzyl
MS molecular sieves
Bu n-butyl
NBS N-bromosuccinimide
BuLi n-butyl lithium
NMR nuclear magnetic resonance
Bu P tri-n-butyl phosphine 3
NMO N-methylmorpholin-N-oxide
Bz benzoyl
NOE nuclear overhauser effect
CAN ceric ammonium nitrate
Nu nucleophile
cat catalytic
p- para
dr diastereomeric ratio
PCC pyridinium chlorochromate
DBU 1,8-Diazabicyclo[4.4.0]
Ph phenyl
undec-7-ene
PPh tri-phenyl phosphine 3
DCE dichloroethane
PMB p-methoxy-benzyl
DEAD diethylazodicarboxylate
pyr pyridine
DMAP N,N-dimethylamino pyridine
quant quantitative
DMF dimethyl formamide
RCM ring closing metathesis
DMS dimethyl sulfide
rt room temperature
ee enantiomeric excess
sat. saturated
eq equivalents
t/(tert) tertiary
EI electronic ionization
TBME tert-butyl-methyl-ether
epi epimer
TBDMS tert-butyldimethylsily
Et ethyl
TBAF tetrabutylammonium fluoride
EWG electron withdrawing group
Tf trifluormethanesulfonate
Glc glucose tBu tert-butyl
h hour
TES triethylsilyl
HAT histone-acetyl-transferase
THF tetrahydrofuran
HPLC high-pressure liquid
TMS trimethylsilyl
chromatography
Tf trifluormethanesulfonate
HRMS high resolution mass
Ts tosyl
spectrometry
X halogens
iPr iso-propyl
IR infrared
L ligand
LAH lithium aluminium hydride
LDA lithiumdiisopropylamide
LiHMDS lithium hexamethyldisilazide
M metal
mCPBA m-chloroperbenzoic acid