Synthetic and stereochemical aspects of intramolecular reactions of α-diazoketones catalysed by rhodium(II) carboxylates

Chapter 1 of this thesis is a brief introduction to the preparation and reactions of α-diazocarbonyl compounds, with particular emphasis on the areas relating to the research undertaken: C-H insertion, addition to aromatics, and oxonium ylide generation and rearrangement. A short summary of catalyst development illustrates the importance of rhodium(II)carboxylates for α-diazocarbonyl decomposition. Chapter 2 describes intramolecular C-H insertion reactions of α-diazo-β-keto sulphones to form substituted cyclopentanones. Rhodium(II) carboxylates derived from homochiral carboxylic acids were used as catalysts in these reactions and enantioselection achieved through their use is discussed. Chapter 3 describes intramolecular Buchner cyclisation of aryl diazoketones with emphasis on the stereochemical aspects of the cyclisation and subsequent reaction of the bicyclo[5.3.0]decatrienones produced. The partial asymmetric synthesis achieved through use of chiral rhodium(II) carboxylates as catalysts is discussed. The application of the intramolecular Buchner reaction to the synthesis of hydroazulene lactones is illustrated. Chapter 4 demonstrates oxonium ylide formation and rearrangement in the decomposition of an α-diazoketone. The consequences of the use of chiral rhodium(II) carboxylates as catalysts are described. Particularly significant was the discovery that rhodium(II) (S)-mandelate acts as a very efficient catalyst for α-diazoketone decompositions, in general. Moderate asymmetric induction was possible in the decomposition of α-diazoketones with chiral rhodium(II) carboxylates, with rhodium(II) (S)-mandelate being one of the more enantioselective catalysts investigated. However, the asymmetric induction obtained was very dependent on the exact structure of the α-diazoketone, the catalyst, and the nature of the reaction. Chapter 5 contains the experimental details, and the spectral and analytical data for all new compounds reported.

Catalyst, additive and substrate effects in intramolecular aromatic additions of alpha-diazoketones

This thesis is focused on transition metal catalysed reaction of α-diazoketones leading to aromatic addition to form azulenones, with particular emphasis on enantiocontrol through use of chiral copper catalysts. The first chapter provides an overview of the influence of variation of the substituent at the diazo carbon on the outcome of subsequent reaction pathways, focusing in particular on C-H insertion, cyclopropanation, aromatic addition and ylide formation drawing together for the first time input from a range of primary reports. Chapter two describes the synthesis of a range of novel α-diazoketones. Rhodium and copper catalysed cyclisation of these to form a range of azulenones is described. Variation of the transition metal catalyst was undertaken using both copper and rhodium based systems and ligand variation, including the design and synthesis of a novel bisoxazoline ligand. The influence of additives, especially NaBARF, on the enantiocontrol was explored in detail and displayed an interesting impact which was sensitive to substituent effects. Further exploration demonstrated that it is the sodium cation which is critical in the additive effects. For the first time, enantiocontrol in the aromatic addition of terminal diazoketones was demonstrated indicating enantiofacial control in the aromatic addition is feasible in the absence of a bridgehead substituent. Determination of the enantiopurity in these compounds was particularly challenging due to the lability of the products. A substantial portion of the work was focused on determining the stereochemical outcome of the aromatic addition processes, both the absolute stereochemistry and extent of enantiopurity. Formation of PTAD adducts was beneficial in this regard. The third chapter contains the full experimental details and spectral characterisation of all novel compounds synthesised in this project, while details of chiral stationary phase HPLC and 1H NMR analysis are included in the appendix.

Ab initio calculations of group 4 metallocene reaction mechanisms: atomic layer deposition and bond activation catalysis

Thin film dielectrics based on titanium, zirconium or hafnium oxides are being introduced to increase the permittivity of insulating layers in transistors for micro/nanoelectronics and memory devices. Atomic layer deposition (ALD) is the process of choice for fabricating these films, as it allows for high control of composition and thickness in thin, conformal films which can be deposited on substrates with high aspect-ratio features. The success of this method depends crucially on the chemical properties of the precursor molecules. A successful ALD precursor should be volatile, stable in the gas-phase, but reactive on the substrate and growing surface, leading to inert by-products. In recent years, many different ALD precursors for metal oxides have been developed, but many of them suffer from low thermal stability. Much promise is shown by group 4 metal precursors that contain cyclopentadienyl (Cp = C5H5-xRx) ligands. One of the main advantages of Cp precursors is their thermal stability. In this work ab initio calculations were carried out at the level of density functional theory (DFT) on a range of heteroleptic metallocenes [M(Cp)4-n(L)n], M = Hf/Zr/Ti, L = Me and OMe, in order to find mechanistic reasons for their observed behaviour during ALD. Based on optimized monomer structures, reactivity is analyzed with respect to ligand elimination. The order in which different ligands are eliminated during ALD follows their energetics which was in agreement with experimental measurements. Titanocene-derived precursors, TiCp*(OMe)3, do not yield TiO2 films in atomic layer deposition (ALD) with water, while Ti(OMe)4 does. DFT was used to model the ALD reaction sequence and find the reason for the difference in growth behaviour. Both precursors adsorb initially via hydrogen-bonding. The simulations reveal that the Cp* ligand of TiCp*(OMe)3 lowers the Lewis acidity of the Ti centre and prevents its coordination to surface O (densification) during both of the ALD pulses. Blocking this step hindered further ALD reactions and for that reason no ALD growth is observed from TiCp*(OMe)3 and water. The thermal stability in the gas phase of Ti, Zr and Hf precursors that contain cyclopentadienyl ligands was also considered. The reaction that was found using DFT is an intramolecular α-H transfer that produces an alkylidene complex. The analysis shows that thermal stabilities of complexes of the type MCp2(CH3)2 increase down group 4 (M = Ti, Zr and Hf) due to an increase in the HOMO-LUMO band gap of the reactants, which itself increases with the electrophilicity of the metal. The reverse reaction of α-hydrogen abstraction in ZrCp2Me2 is 1,2-addition reaction of a C-H bond to a Zr=C bond. The same mechanism is investigated to determine if it operates for 1,2 addition of the tBu C-H across Hf=N in a corresponding Hf dimer complex. The aim of this work is to understand orbital interactions, how bonds break and how new bonds form, and in what state hydrogen is transferred during the reaction. Calculations reveal two synchronous and concerted electron transfers within a four-membered cyclic transition state in the plane between the cyclopentadienyl rings, one π(M=X)-to-σ(M-C) involving metal d orbitals and the other σ(C-H)-to-σ(X-H) mediating the transfer of neutral H, where X = C or N. The reaction of the hafnium dimer complex with CO that was studied for the purpose of understanding C-H bond activation has another interesting application, namely the cleavage of an N-N bond and resulting N-C bond formation. Analysis of the orbital plots reveals repulsion between the occupied orbitals on CO and the N-N unit where CO approaches along the N-N axis. The repulsions along the N-N axis are minimized by instead forming an asymmetrical intermediate in which CO first coordinates to one Hf and then to N. This breaks the symmetry of the N-N unit and the resultant mixing of MOs allows σ(NN) to be polarized, localizing electrons on the more distant N. This allowed σ(CO) and π(CO) donation to N and back-donation of π*(Hf2N2) to CO. Improved understanding of the chemistry of metal complexes can be gained from atomic-scale modelling and this provides valuable information for the design of new ALD precursors. The information gained from the model decomposition pathway can be additionally used to understand the chemistry of molecules in the ALD process as well as in catalytic systems.

The development of novel chiral tethers for controlling intramolecular aryl-aryl coupling and their application in the synthesis of gomisin M1 and analogues

The primary focus of this thesis was the development of a novel chiral tether that could be used to control axial chirality around a newly formed aryl-aryl bond, and the extension of this methodology to the model synthesis of gomisin M1. In chapter 1, a review detailing the use of chiral tethers in the synthesis of atropisomers is discussed. The use of a variety of chiral molecules including 1,2-diols, 1,3-diols and other diol-based tethers, as well as amine-based and miscellaneous tethers are detailed. In chapter 2, the rationale behind the design of our novel molecular tethers, along with the subsequent synthesis of three chiral 1,3-diol-based tethers, is outlined. The method by which the enantiopurity of these diols was determined is also reviewed. This chapter also includes the attempted Mitsunobu and intramolecular couplings in the model synthesis of BINOL. Chapter 3 discusses the synthesis of suitable aryl halide substrates, and their employment in the attempted tether-controlled asymmetric model synthesis of gomisin M1. A comprehensive investigation into the attempted intramolecular biaryl coupling of these tethered substrates is also included. The non-stereoselective model synthesis of gomisin M1 is outlined in chapter 4. The installation of the desired biaryl linkage and the subsequent attempted intramolecular McMurry couplings are discussed. The impact of different protecting groups in the molecule on the intramolecular McMurry reaction is also outlined. Chapter 5 details the full experimental procedures, including spectroscopic and analytical data for the compounds prepared during this research.