Novel Applied Hydroamination Novel Calcium Comp Applied to Hydroamination Calcium ...

284 Pages·2012·5.37 MB·English

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Abstract
This Thesis discusses the synthesis, characterisation, and reactivity studies of a range of
new chiral calcium complexes supported by various polydentate N-donor ligands and their
suitability as catalysts for intramolecular hydroamination.
Chapter One outlines the case for developing organocalcium complexes, including a
general overview of their current application to a variety of heterofunctionalisation
reactions.
Chapter Two introduces the chiral ethylene diamines which are extensively used as
calcium supporting ligands and later as precursors for the synthesis of bisimidazoline and
potential imoxazoline ligands. Chapter Two provides details of the diamine synthesis and
includes studies related to racemisation concerns of the chiral centre.
Chapter Three discusses novel calcium complexes supported by the chiral ethylene
diamine analogues presented in Chapter Two. Complex synthesis, characterisation, and
catalytic performance in intramolecular hydroamination is probed and discussed.
Chapter Four details a range of new bisimidazoline ligands and their employment as
supporting ligands on calcium. The catalytic performance of the resulting complexes in
intramolecular hydroamination is subsequently analysed and discussed.
Chapter Five investigates the attempted development of a total synthetic pathway to a new
class of imoxazoline ligand and related issues.
Chapter Six contains all experimental procedures, characterising data pertaining to all new
compounds and complexes presented in this Thesis.
Appendices A-K contain additional catalytic figures and tables of crystallographic data for
all new crystallographically characterised compounds. Summary sheets of every literature
and new compound presented mentioned in this Thesis are also included, along with copies
of both printed publications resulting from this Thesis at the time of submission.

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Acknowledgements
Firstly I must express my deepest gratitude to my supervisor Dr. Benjamin Ward. I will
never forget the first time I stepped into your office to discuss a PhD position within your
group nor shall I forget your boundless help, advice, and optimism, which truly are virtues
that I greatly admire and look up to.
I would like to thank the Ward group members both past and present. The last few years
working with and alongside each of you in the laboratory has left me with many fond
memories. In no particular order: Stacey Bennett for your help and kindness with so many
aspects during my studies. Tom O’Brien for your humour and excellent company, which
was especially welcomed on the many occasions when working late. I must also thank
Angelica Orsi, Fred Seeley, David Collis, Kate Smith, Matt Craig, Matt O’Brien, Scott
Board and Victoria Hallhead for all your individual contributions when assisting me on the
challenging synthetic side of my work. To Dr. Andy Hallett and Dr. Tracy Nixon, thank
you both for your time and advice.
I would not have made it through the past three years without the support and friendship of
Wei Ye Lu, Steven Robert Hughes, Benjamin Palmer, Andreas Schneeman, Daniel
Russell, Dominic Caswell, Chris Mackay, Wilson Fung, Joanna Ha, Iris Cheung, Diane
Chung and Mark Stevenson. I am especially grateful to Kim MacPhee, for her endless
encouragement.
Throughout my doctoral studies I have had the pleasure of knowing Dr. Sanka
Meenakshisundaram, Dr. Yulia Rogan, Dr. Barry Dean, Dr. Tanya Kotionova and Piotr
Rutkowski. I have very much enjoyed the time spent with you all, although this group
would not be complete without mention of Ewa Nowicka; of whom I am thankful for the
many discussions on the delights of the continent with.
Particular thanks must go to Dr. Robert Jenkins for his help, patience, and advice related to
the NMR spectroscopy that constitutes such a large proportion of this Thesis. I would also
like to convey my appreciation to Dr. Benson Kariuki for assistance in obtaining the
crystallographic data presented in this Thesis. I extend my thanks to Robin Hicks and Dave
Walker for their sterling work with respect to the Mass Spectrometry analysis that
accompanies this Thesis. I am also ever appreciative of Ricky Fearne’s glassblowing
expertise that without many of my experiments would not have been possible.
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To Dr. Huw Tallis, Dr. Angelo Amoroso, Dr. James Knight, Dr. Paul Newman, Dr. Ian
Morgan, Dr. Tom Tatchell and Dr. Anthony Thompson; I am indebted to each of you for
the time you spent with me discussing my work, my frustrations, or my future aspirations.
The ladies and gentlemen of the Chemical Stores, Technical Services and Administrative
Staff: Gary Coleman, Jamie Cross, Sham Ali, John Cavanagh, Alun Davies, Steven Morris,
Terrie Dumelow, Matthew James and Alison Rowlands; It has been a pleasure to know
you all during my post-graduate years at Cardiff and I am ever thankful to each of you for
the help and backing you have given me during this time.
I would especially like to say to Malcolm Bryant that it has been an enjoyment to work
with you and to have known you during the last three years. I am in your debt for the
support you have rendered.
I never anticipated taking on a part time job during my final year of research, however the
year I spent working at the Barocco Bar in Cardiff’s Highstreet will not easily be forgotten.
The hard work, the good times, nor the friends I made; Caroline Venter, Carl Rowlands,
Gareth Rees, Vanessa Brown, James Moinet, Arnaud Ritter, Rhys Littlejohns, Josh
Windsor, Chris Mcilquham, Vikki Paskell, Sam Spierling, Gemma Dick, Jess Magness,
Tori Cowley, Dan Busby and Yusef Canning.
Finally I wish to thank my family, Mum and Dad, Andy, Lind, and Catherine for your
unwavering support. You have all offered your help to me over the many years, which has
not gone amiss.
I am grateful to the EPSRC and Leverhulme Trust for providing the funding which allowed
me to accomplish the work described within this Thesis.
Thank you all.

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Abbreviations
General
Å Angstrom
Ac acetate group, [CH COO]-
3
acac acetylacetonate
AE Alkaline Earth
Ar aryl
BBL β-butyrolactone
BINOL 1,1’-bi-2-napthol
BDI β-diketimidato
Boc tert-butyloxycarbonyl
BOX bisoxazoline
tBu tert-butyl
°C degrees Celsius
ca. circa, about
cf. compared with
ε-CL ε-caprolactone
COD cyclooctadiene
Cp* cyclopentadiene anion
d day(s)
DIPEA diisopropylethylamine
DMAP N,N-dimethylaminopyridine
DMAT 2-N(CH ) -α-Si(CH ) -CH(C H )
3 2 3 3 6 5
DME 1,2-dimethoxyethane
DPE 1,1-diphenylethylene
Dpp diphenylphosphinyl group
e.e enantiomeric excess
E.I. Electron Impact
Et ethyl
g gram
h hour(s)
HBCat Catecholborane, (1,3,2-Benzodioxaborole)
iv
HBPin pinacolborane, (4,4,5,5-tetramethyl-1,3,2-dioxaborolane)
HMDS hexamethyldisilazane, [N(Si(Me ) ]-
3 2
HMPA Hexamethylphosphoramide, (Me N) PO
3 3
HNNR ethylene 1,2-diamine
iBCF iso-butylchloroformate
IMOX imoxazoline
ipso- ipso substituted
L mono-anionic supporting ligand
2
LA lactide
Ln lanthanide
M metal atom
m- meta substituted
Me methyl
MS Mass Spectrometry
min minute(s)
NMM N-methylmorpholine
o- ortho substituted
OTf triflate group, [CF SO ]-
3 3
p- para substituted
PDI Polymer Dispercity Indices
Ph phenyl
Pht phthalic anhydride moiety
PPN+ µ-nitrido-bis(triphenylphosphine)1+
iPr iso-propyl
py pyridine
py-Box pyridinebisoxazoline
R rectus enantiomer
R alkyl or aryl group
R-BIM bisimidazoline
R-MIM mono-imidazoline imoxazoline precursor
ROP Ring-Opening Polymerisation
S sinister enantiomer
sec second(s)
v
ST styrene
TBTU O-(benzotriazol-1-yl)-N,N,N’,N’-tetramethyluronium
tetrafluoroborate
tBu tert-Butyl
TFPB tetrakis(3,5-bistrifluoromethylphenly)borate
THF tetrahydrofuran
TMC trimethylenecarbonate
TMS trimethylsilane
Tpm HC(3,5-dimethylpyrazole)
3
Ts tosyl group, (CH C H SO )
3 6 4 2
vs. Versus
Viz. videlicet, that is to say
X1 mono-anionic σ-bound substituent

Nuclear Magnetic Resonance Spectroscopic Data
app. apparent
br. broad
13C-{1H} proton-decoupled 13C
COSY Correlation SpectroscopY
d doublet
δ chemical shift in ppm
J coupling constant
HMBC Heteronuclear Multiple Bond Connectivity
HSQC Heteronuclear Multiple Quantum Coherence
Hz Hertz
m multiplet
MHz Megahertz
NMR Nuclear Magnetic Resonnance
nOe nuclear Overhauser effect
ppm parts per million
q quartet
quin. quintet
vi
s singlet
sept. septet
t triplet

Infrared Spectroscopic Data
br broad
cm-1 wave number
IR Infrared
m medium
ʋ frequency
s strong
w weak

Notes about numbering of literature compounds described in this Thesis
Literature compounds described in this Thesis are sequentially numbered 1.X, 2.X, 3.X,
4.X, and 5.X, according to the Chapter in which they are first presented. The new
compounds expressed in this Thesis are numbered 1-16.

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Contents

Chapter One – Organocalcium Catalysis
1.1 The Case for Calcium 2
1.1.1 Taming Calcium 4
1.2 Calcium in Catalysis 5
1.2.1 Hydroamination 6
1.2.1.1 Intermolecular Hydroamination 13
1.2.1.2 Asymmetric Hydroamination of Alkenes 16
1.2.1.3 Intermolecular Hydroamination of Isocyanates and
Carbodiimides 21
1.2.2 Hydrosilylation 26
1.2.2.1 Asymmetric Hydrosilylation of Alkenes 32
1.2.3 Hydrophosphination 33
1.2.3.1 Hydrophosphination of Carbodiimides 38
1.2.4 Hydrogenation 41
1.2.5 Hydroboration of Alkenes 43
1.3 References 47

Chapter Two – Chiral Ethylene Diamine Synthesis
2.1 Introduction 54
2.2 Route One – Acid Anhydride Intermediate 57
2.2.1 Amino Acid Protection 57
2.2.2 Amidation of N-phthaloyl valine via an Acid Anhydride Route 58
2.3 Route Two – Aziridine Intermediate 60
2.3.1 Catalysed Aziridine Ring-Opening 61
2.4 Route Three – Acid Chloride Intermediate 62
2.4.1 Amidation via an Acid Chloride 64
2.4.2 Removal of Phthalamide Protecting Group 66
2.4.3 Amide Reduction 68
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2.5 Racemisation of the Chiral Centre 72
2.6 References 77

Chapter Three – Calcium Complexes Supported by Diamine Ligands
3.1 Introduction 80
3.2 Preparation of Calcium Complexes Supported by Diamine Ligands 82
3.3 Spectroscopic Characterisation 83
3.4 DFT 88
3.5 Intramolecular Hydroamination Catalysis 90
3.5.1 Catalytic Performance and Enantioselectivity 94
3.6 References 100

Chapter Four – Chiral Bisimidazoline Supported Calcium Complexes
4.1 Introduction 103
4.2 Ligand Synthesis and Characterisation 108
4.2.1 Ligand Bridge Component 109
4.2.2 Structural Tautomers and Evidence of Diastereoisomerism 112
4.3 Chiral Calcium Complexes Supported by Bisimidazolines 113
4.3.1 Complex Synthesis 113
4.3.2 Complex Characterisation 115
4.4 Complex Redistribution 118
4.5 DFT 124
4.6 Catalytic Performance 126
4.6.1 Enantiomeric Excess Determination 127
4.6.2 Kinetics of Catalysis 127
4.6.3 Catalyst Performance Analysis 130
4.7 References 136

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