Department of Chemistry Towards the Synthesis of Isocoronene Iain William Currie This thesis is presented for the Degree of Doctor of Philosophy of Curtin University April 2018 Declaration To the best of my knowledge and belief this thesis contains no material previously published by any other person except where due acknowledgement has been made. This thesis contains no material which has been accepted for the award of any other degree or diploma in any other university. Signature: Date: i Abstract The concept of aromaticity and its implications are fundamentally important to a wide range of applied sciences involving organic molecules. Aromaticity arises from the delocalisation of electrons through a cyclic conjugated system known as a conjugated circuit. Monocyclic aromatic compounds possess a single conjugated circuit while polycyclic aromatic hydrocarbons (PAHs) may have numerous potential conjugated circuits. The aromaticity of PAHs is complicated by the presence of multiple conjugated circuits which may have varying contribution to the overall properties depending on several factors such as geometry and topology. Isocoronene 105 is one example of a PAH classified as a non-benzenoid corannulene. Isocoronene is unique among corannulenes since the conjugated circuits are restricted to the peripheral and central rings only. Isocoronene has been used as a model compound for computational studies into aromaticity and may provide the first example of a superaromatic molecule. The synthesis of novel aromatic structures such as isocoronene is essential in providing unambiguous empirical data which can be used to verify and develop computational methods. In addition, the development of new synthetic methodologies towards PAHs is important in the field of organic electronics. The following thesis describes synthetic strategies and experimental work towards the synthesis of isocoronene. The initial strategy for the synthesis of isocoronene was through a threefold intramolecular Buchner reaction. The key intermediate triphenylene diazoketone 156 was synthesised from methyl anthranilate 138 in six steps. Rhodium catalysed decomposition of the diazoketone gave coronene 159 in high yield as a single major product with no detectable amount of the desired isocoronene derivative. The formation of coronene was attributed to an intramolecular C-H insertion reaction. The desired Buchner ring expansion may be disfavoured due to the electron ii withdrawing carbonyl groups of 156. The synthesis of coronene 159 through intramolecular C-H insertion has not previously been reported in the literature. This method could be applied to the synthesis of coronene derivatives with substitution patterns and functional groups that are not accessible through known methods. The second approach towards isocoronene involved an intramolecular aldol condensation of trindane derivative 218. To this end, the norbornadiene cyclotrimer 250 was synthesised in 6 steps from dicyclopentadiene 242 and trichloroethylene 243. Several attempts were made at the oxidative ring opening of 250 resulting in a product that could not be characterised by NMR. iii The final synthetic strategy towards isocoronene utilised the trindene ring structure as a key intermediate. The reactivity of trindene 230 towards electrophiles was investigated with the aim of introducing benzylic linking groups for the construction of the isocoronene framework. Trindene was found to react with aromatic aldehydes to give the symmetrical trifulvene product 278, however no reaction was observed with aliphatic aldehydes. The aryl substituents of 278 are not suitable as linking groups and attempts at introducing linking groups to the aryl trifulvene were not successful. The synthesis of trifulvene is the first reported bond forming reaction with trindene and represents a new class of fulvene structures. An alternative approach to trindene derivatives was explored through the use of perchlorotrindene 320. Perchlorotrindene was synthesised in a single step through the cyclotrimerisation reaction of perchlorocyclopentadiene 319. The geminal dichloro groups of perchlorotrindene were then hydrolysed with silver nitrate to give perchlorotrindenone 324. The reactivity of perchlorotrindenone towards carbon nucleophiles was subsequently investigated with the objective of introducing substituents at the benzylic positions. Perchlorotrindenone was found to undergo rapid decomposition in the presence of hard and soft carbon nucleophiles. It was concluded that perchlorotrindenone is unstable under basic reaction conditions and so alternative bond forming reactions were considered. iv The use of metal catalysed cross coupling reactions was subsequently examined as a method of introducing linking groups to perchlorotrindenone 324. The cross coupling reaction was expected to occur selectively at the benzylic vinyl chloride positions due to the electron withdrawing effect of the carbonyl. The reactivity of perchlorotrindenone towards the Suzuki coupling reaction was initially investigated using phenylboronic acid. Under standard reaction conditions, perchlorotrindenone reacted with phenylboronic acid to yield the desired triphenyl-trindenone 335 (R = phenyl). This demonstrates the feasibility of introducing the desired carbon chain to perchlorotrindenone through the use of a linear coupling partner. The use of a suitably functionalised coupling partner would open the possibility for an intramolecular ring closing reaction to access the isocoronene ring system. v Acknowledgements I would like to thank my supervisor Dr Alan Payne for his advice and guidance throughout my studies. It was Alan’s enthusiasm and knowledge which inspired me to pursue a doctoral degree in organic chemistry. I would also like to thank my cosupervisor Associate Professor Mauro Mocerino for providing valuable feedback during the writing process. In addition, I am grateful for the funding provided through the Australian Postgraduate Award program which has been essential during my PhD studies. Finally, I would like to thank my friends and family for their support and understanding throughout the entire process. vi Contents 1 Introduction 1 1.1 History of aromaticity 1 1.2 Aromaticity of non-benzenoid compounds 4 1.3 Aromaticity of polycyclic aromatic hydrocarbons 6 1.4 Clar’s rule 7 1.5 Aromaticity of corannulene 10 1.6 Scholl and Meyer synthesis of coronene 11 1.7 Newman synthesis of coronene 14 1.8 Scott synthesis of coronene 17 1.9 Aromaticity of coronene 19 1.10 Aromaticity of azulene 20 1.11 Plattner synthesis of azulene 21 1.12 Arnold synthesis of azulene 24 1.13 Ziegler-Hafner synthesis of azulene 27 1.14 Scott synthesis of azulene 28 1.15Aromaticity of azupyrene 29 1.16 Anderson synthesis of azupyrene 30 1.17 Jutz synthesis of azupyrene 33 1.18 Aromaticity of isocoronene 35 1.19 Attempted synthesis of isocoronene 38 1.20 Project aims 42 2 Buchner ring expansion approach 46 2.1 Proposed synthetic pathway 47 2.2 Synthesis of the diiodide 48 2.3 Synthesis of triphenylene diazoketone 52 2.4 Buchner ring expansion 61 2.5 Diazoketone derivatives 65 vii 3 Norbornadiene trimer approach 92 3.1 Hexabromotrindane 93 3.2 Ullmann coupling cyclotrimerisation 99 3.3 Alternative approach to the norbornadiene trimer 102 3.4 Ring cleavage of the norbornadiene trimer 107 4 Trindene approach 114 4.1 Trindene trianion 115 4.2 Alkylation of trindene 118 4.3 Trifulvene 116 4.4 Condensation reactions of indene and trindene 127 4.5 Nucleophilic addition to fulvenes 134 4.6 Trindenone 143 4.7 Perchlorotrindene 147 5 Conclusions 161 6 Experimental 171 References 207 viii List of abbreviations [M+H]+ Mass of protonated molecular ion Ac Acetyl AcOH Acetic acid Ar Aryl ASE Aromatic stabilisation energy ATR IR Attenuated total reflectance infrared br broad Bu Butyl conc. concentrated CuTC copper(I) thiophenecarboxylate d doublet DBU 1,8-Diazabicyclo[5.4.0]undec-7-ene DCM Dichloromethane DDQ 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone DEPT Distortionless enhancement by polarization transfer DIBAL Diisobutylaluminum hydride DMAD Dimethyl acetylenedicarboxylate DMF N,N-Dimethylformamide DMSO Dimethylsulfoxide dppe 1,3-Bis(diphenylphosphino)ethane eq Equivalents ESI Electron spray ionisation Et Ethyl Et2O Diethyl ether Et3N Triethylamine EtOAc Ethyl acetate EtOH Ethanol hfacac Hexafluoroacetylacetonate HRMS High resolution mass spectrometry hrs hours HSAB Hard-soft acid base theory ix HWE reaction Horner–Wadsworth–Emmons reaction hυ Photochemical reaction IBX 2-Iodoxybenzoic IR Infrared J Coupling constant LDA Lithium diisopropylamide LG Leaving group m Multiplet m/z Mass divided by charge Me Methyl MeCN Acetonitrile MeOH Methanol Ms Methanesulfonyl N.R No reaction observed NBS N-Bromosuccinimide n-BuLi n-Butyllithium NMP N-Methylpyrolidinone NMR Nuclear magnetic resonance Nu- Nucleophile o Ortho OTf Trifluoromethanesulfonate p para PAH Polycyclic aromatic hydrocarbon Ph Phenyl ppm Parts per million RSE Resonance stabilisation energy r.t Room temperature RF Retardation factor s Singlet t- Tertiary t Triplet TBAF Tetrabutylammonium fluoride t-BuOK Potassium tert-butoxide TFA Trifluoroacetic acid x TFAA Trifluoroacetic anhydride THF Tetrahydrofuran TLC Thin layer chromatography TMS Trimethylsilyl Ts/tosyl p-Toluenesulfonyl TsO/tosylate p -Toluenesulfonate TsOH p -Toluenesulfonic acid w.r.t With respect to δ Chemical shift in ppm Δ Heating xi Chapter 1 Introduction Aromaticity is a key element in organic chemistry since it is one of the most powerful thermodynamic driving forces