Homogeneous Hydrogenation of Electron-Deficient Alkenes by Using Iridium-Complexes

322 Pages·2009·3.12 MB·English

by  Semeniuchenko, Volodymyr

HOMOGENEOUS HYDROGENATION OF
ELECTRON-DEFICIENT ALKENES BY USING
IRIDIUM-COMPLEXES

Dissertation
zur Erlangung des akademischen Grades
eines Doktors der Naturwissenschaften
an der Universität Konstanz

vorgelegt von

Volodymyr Semeniuchenko

Konstanz 2009
Tag der mündlichen Prüfung: 19.05.2009
Erstgutachter: Prof. Dr. Ulrich Groth
Zweitgutachter: Prof. Dr. Helmut Fischer
Prüfungsvorsitzender: Prof. Dr. Thomas Exner
For my wonderful family
The present work has been completed from October 2005 to February 2009 in the workgroup
of Prof. Ulrich M. Groth, Department of Chemistry of the University of Konstanz, within the
partnership between the University of Konstanz and the National Taras Shevchenko
University Kiev.

Special thanks to:
Prof. Dr. Ulrich Groth for giving me the opportunity to work in his group, for discussions
concerning my work and for his entire support;
Prof. Dr. Volodymyr Khilya for the interesting topic, for discussions concerning my work and
for his entire support;
Prof. Dr. Thomas Exner for quantum-chemical computations, theirs interpretation and
discussions;
Prof. Dr. Helmut Fischer, for writing the second evaluation;
Michael Burgert, Victor Iaroshenko, Dr. Thomas Huhn, Anton Kotljarov, Dr. Markus
Ringwald, Dr. Olga Tšubrik, Dr. Christian Kesenheimer, Aleksei Bredihhin, Kateryna Gura,
Angelika Früh, Steffen Lang and all the members of workgroup Groth for interesting
discussions and useful comments regarding the topic of the work and to Milena Quentin for
all the help she gave me;
Anke Friemel, Ulrich Haunz, Prof. Dr. Heiko Möller and Andreas Berkefeld for
measurements and discussions of NMR-spectra;
Michael Burgert, Rheinhold Weber, Dmitry Galetsky and Sascha Keller for measurements
and discussions of mass-spectra;
Thomas Haas for a possibility to perform column chormatography at low temperature;
Qiong Tong and Yan Wang for Chinese translations, Stelmakh Svetlana and Christian
Kesenheimer for Japanese translations;
All my friends in Konstanz with whom I had a wonderful time here;
Last but not least I wish to thank and to express my deep gratitude to my family and my
parents for supporting and encouraging me during this time.

The research would not have been possible without the scholarships on part of the Herbert-
Quandt Stiftung der Altana AG (now Nycomed) and the Deutsche Akademische
Austauschdienst (DAAD). The scholarships are kindly acknowledged.
This dissertation has been published in part, and presented at the following conferences:

PUBLICATIONS

Volodymyr Semeniuchenko, Volodymyr Khilya, Ulrich Groth. Nucleophilic Homogeneous
Hydrogenation by Iridium Complexes, Synlett, 2009, 2, 271-275

CONFERENCE PRESENTATIONS

Volodymyr Semeniuchenko, Volodymyr Khilya, Ulrich Groth. Nucleophilic homogeneous
hydrogenation by Ir-complexes, 10th Frühjarssymposium, 27th-29th March 2008, Rostock
(Germany).

Volodymyr Semeniuchenko, Volodymyr Khilya, Ulrich Groth. Nucleophilic homogeneous
hydrogenation by Ir-complexes, International Synposium on Homogeneous Catalysis ISHC-
XVI, 6th-11th July 2008, Florence (Italy).

Volodymyr Semeniuchenko, Volodymyr Khilya, Ulrich Groth. High-efficient Synthesis of
(Phosphanodihydrooxazole) (1,5-cyclooctadiene) Iridium Complexes, 11th
Frühjarssymposium, 11th-14th March 2009, Essen (Germany).
TABLE OF CONTENTS I
TABLE OF CONTENTS

1 INTRODUCTION..................................................................................................1
1.1 Synthesis of chroman-4-ons by reduction of chromones.........................................1
1.1.1 Hydrogenation of chromones...................................................................................4
1.1.1.1 With palladium on charcoal.....................................................................................4
1.1.1.2 With palladium on the other support or elemental palladium................................11
1.1.1.3 With platinum.........................................................................................................13
1.1.1.4 With Raney-Nickel.................................................................................................16
1.1.2 Transfer hydrogenation of chromones on palladium.............................................18
1.1.3 Reduction of chromones with complex hydrides...................................................22
1.1.4 Reduction of chromones with diisobutylaluminium hydride.................................28
1.1.5 Reduction of flavonols with sodium dithionite......................................................29
1.1.6 Other methods for the reduction of chromones......................................................30
1.1.7 Conclusion..............................................................................................................36
1.2 Synthesis of chroman-2-ons by reduction of coumarins........................................36
1.2.1 Hydrogenation of coumarins..................................................................................39
1.2.1.1 With palladium on charcoal...................................................................................39
1.2.1.2 With palladium on the other support or elemental palladium................................47
1.2.1.3 With platinum.........................................................................................................50
1.2.1.4 With nickel.............................................................................................................52
1.2.2 Transfer hydrogenation of coumarins....................................................................53
1.2.3 Reduction of coumarins with metals......................................................................56
1.2.4 Reduction of coumarins with complex hydrides....................................................60
1.2.5 Homogeneous hydrogenation of coumarins...........................................................64
1.2.6 Electrochemical reduction......................................................................................67
1.2.7 Other methods for the reduction of coumarins.......................................................68
1.2.8 Conclusion..............................................................................................................71
1.3 Biologically active compounds: racemates versus pure enantiomers....................72
1.4 Homogeneous catalytic hydrogenation of alkenes.................................................75
1.4.1 Homogeneous hydrogenation of alkenes: rhodium catalysis.................................76
1.4.2 Homogeneous hydrogenation of alkenes: iridium catalysis...................................79
1.4.3 Homogeneous hydrogenation of alkenes: ruthenium and osmium catalysis.........81
TABLE OF CONTENTS II
1.4.4 Homogeneous hydrogenation of alkenes: metallocenes........................................84
1.4.5 Homogeneous hydrogenation of alkenes: other metals..........................................85
1.5 Enantioselective homogeneous catalytic hydrogenation........................................86
2 OBJECTIVES.......................................................................................................92
3 RESULTS AND DISCUSSION...........................................................................93
3.1 Attempts to hydrogenate model flavonoids...........................................................93
3.2 Attempts to prepare a heterogenized catalyst.......................................................100
3.3 Nucleophilic hydrogenation of 7-methoxyisoflavone..........................................110
3.4 Nucleophilic hydrogenation: catalyst screening..................................................114
3.5 Nucleophilic hydrogenation of various substrates...............................................129
3.6 Proposed mechanism of nucleophilic hydrogenation...........................................135
3.7 Hydrogenation of 7-methoxy-3-(pyridin-2-yl)chromone.....................................146
4 SUMMARY.........................................................................................................152
5 ZUSAMMENFASSUNG...................................................................................159
6 OUTLOOK.........................................................................................................166
7 EXPERIMENTAL SECTION..........................................................................169
7.1 Attempts to hydrogenate model flavonoids.........................................................170
7.2 Attempts to prepare a heterogenized catalyst.......................................................182
7.3 Nucleophilic hydrogenation of 7-methoxyisoflavone..........................................186
7.4 Nucleophilic hydrogenation: catalyst screening..................................................188
7.5 Nucleophilic hydrogenation of various substrates...............................................228
7.6 Proposed mechanism of nucleophilic hydrogenation...........................................234
7.7 Hydrogenation of 7-methoxy-3-(pyridin-2-yl)chromone.....................................275
8 REFERENCES...................................................................................................283
ABBREVIATIONS III

ABBREVIATIONS

Ac Acetyl (actinium is not mentioned in the dissertation)
ATR Attenuated Total Reflectance
B3LYP Becke 3-Parameter (Exchange), Lee, Yang and Parr (correlation;
density functional theory)
BARF Tetrakis(3,5-bis(trifluoromethyl)phenyl) borate
9-BBN 9-Borabicyclo[3.3.1]nonane
BEMP 2-tert-Butylimino-2-diethylamino-1,3-dimethyl-perhydro-1,3,2-
diazaphosphorin
BINAP 2,2`-Bis(diphenylphosphino)-1,1`-binaphtyl
borsm Based on recovery of starting material
BTED Bis[t-butylthio]ethane-diborane
iBu iso-Butyl
nBu n-Butyl
sBu sec-Butyl
tBu tert-Butyl
C^N Chelating ligand, having coordinations sites at carbon (carbene) and
on nitogen atoms
C^P Chelating ligand, having coordinations sites at carbon (carbene) and
on phosphorus atoms
CD Circular Dichroism
COD 1,5-Cyclooctadiene
COE Cyclooctene
COSY COrrelation SpectroscopY
COX Cyclooxygenase
CP Cross-Polarization
CPTOSS Cross-Polarization TOtal Side-band Suppresion
CTH Catalytic Transfer Hydrogenation
Cy Cyclohexyl
de Diastereomeric excess
DFT Density Functional Theory
ABBREVIATIONS IV
DIPEA Diisopropylethylamine, Hünig’s base
DMF Dimethylformamide
DMSO Dimethylsulfoxide
DPPB 1.4-Bis(diphenylphosphinyl)butane
DPPP 1.4-Bis(diphenylphosphinyl)propane
ee Enantiomeric excess
ESI ElectroSpray Ionisation
ESP Electro-Static Potential
Et Ethyl
EWG Electron Withdrawing Group
FT-ICR Fourier Transfrom - Ion-Cyclotrone Resonance
GC/MS Gas-Chromatogphy with Mass Selective detector
GLC Gas-Liquid Chromatography
GLYMO Glycidoxypropyltrimethoxysilane (trimethoxy(3-(oxiran-2-
ylmethoxy)propyl)silane)
HMBC Heteronuclear Multiple Bond Correlation
HMDS Hexamethyldisilazane
HOMO Highest Occupied Molecular Orbital
HRMS High-Resolved Mass-Spectrometry
HSQC Heteronuclear Single Quantum Coherence
HTC High Throughput Computation
HTE High Throughput Experimentation
HTS High Throughput Screening
IL Interleukin
IMe 1,3-dimethylimidazol-2-ene
IR Infrared
LAH Lithium tetrahydridoaluminate, LiAlH
4
LHMDS Lithium hyxamethyldisilazide
LOX Lypooxygenase
LSR Lantanoid Shift Reagent
LUMO Lowest Unoccupied Molecular Orbital
MAS Magic Angle Spinning
Me Methyl
ABBREVIATIONS V
MeO Methoxy
MOM Methoxymethyl
MS Mass-Spectrometry
MW Microwave
N/A Not available
Na EDTA Dinatrium salt of ethylendiamine tetraacetic acid
2
NADH Nicotinamide Adenine Dinucleotide carrying two electrons and
bonded with H+
NADPH Nicotinamide adenine dinucleotide phosphate carrying two electrons
and bonded with H+
NBD Nor-bornadiene
NBO Natural Bond Orbital
NHC N-Hetecocyclic Carbene
NMR Nuclear Magnetic Resonance
NOESY Nuclear Overhauser Effect SpectroscopY
NPA Natural Population Analysis
P^N Chelating ligand, having coordinations sites at phosphorus and on
nitogen atoms
P^P Chelating ligand, having coordination sites at both phosphorus atoms
PCC Pyridinium chlorochromate
PM3 Parameterized Model number 3 (semi-empirical method, based on
Neglect of Differential Diatomic Overlap)
Ph Phenyl
Phox Phosphinooxazoline
iPr iso-Propyl
Py Pyridine
Rf Retention factor
ROESY Rotational nuclear Overhauser Effect SpectroscopY
r.t. Room temperature
Tf Triflyl
TFA Trifluoroacetic acid
THF Tetrahydrofuran
TLC Thin-Layer Chromatography