Development of sustainable catalytic methods for organic synthesis

This thesis covers two separate projects, but both of which can be linked by the overall aim to develop sustainable catalytic methodology for use in organic synthesis. A concerted effort has been made to move away from procedures within organic chemistry that use non-renewable expensive and toxic materials as reagents and catalysts, particularly those containing second and third row transition metals, and instead to develop processes that utilise sustainable, abundant and inexpensive reagents, such as base-metals and main group elements. The first project was the attempted development of an oxidative ring contraction of aromatic compounds, with the goal of applying it in the biomimetic total synthesis of fatouapilosin. The second project concerned the development of the borane-catalysed enantioselective hydroboration and reduction of propargylic ketones. Chapter 1 is an introduction to the first project, giving details regarding the isolation and proposed biosynthetic route to fatouapilosin, as well as giving an overview of the area of biomimetic total synthesis. The oxidative ring contraction reaction, the use of iron and copper for oxidation of organic compounds, and the potential of phenols as a renewable source of carbon are also discussed. Chapter 2 describes the first total synthesis of the coumarin natural product brosiparin, an important precursor in the proposed synthesis of fatouapilosin, which was the planned substrate on which to develop a method of oxidative ring contraction. Brosiparin was successfully prepared in a three-step procedure from pyrogallol, with an initial double demethylation followed by an O-prenylation, then a tandem Wittig olefination/para- Claisen rearrangement/lactonisation sequence. Chapter 3 focuses on the oxidation chemistry of brosiparin, and the efforts to develop a reliable method of oxidative ring contraction. Unfortunately trials with a wide variety of oxidising agents, including iron and copper catalysts, did not result in the desired transformation. The use of phenyliododiacetate (PIDA) enabled us to access a masked ortho-quinone compound, from which further reactions were attempted, including an interesting aryl-aryl coupling reaction, but the unprotected ortho-quinone proved very unstable and difficult to work with. Chapter 4 covers the second project, and starts with a broad introduction to the area of hydroboration, followed by a more focused look at enantioselective hydroboration and reduction of ketones. The successful development of an enantioselective reduction of propargylic ketones using substoichiometric myrtanyl borane with stoichiometric HBpin is then described. The reaction was shown by 1H and 11B NMR studies to proceed via a transborylation mechanism, and was applied to other propargylic ketone substrates

A boron-oxygen transborylation strategy for a catalytic Midland reduction

The enantioselective hydroboration of ketones is a textbook reaction requiring stoichiometric amounts of an enantioenriched borane, with the Midland reduction being a seminal example. Here, a turnover strategy for asymmetric catalysis, boron.oxygen transborylation, has been developed and used to transform the stoichiometric borane reagents of the Midland reduction into catalysts. This turnover strategy was demonstrated by the enantioselective reduction of ketones, including derivatives of biologically active molecules and those containing reducible groups. The enantioenriched borane catalyst was generated in situ from commercially available reagents, 9-borabicyclo[3.3.1]nonane (H-B-9-BBN) and β-pinene, and B.O transborylation with pinacolborane (HBpin) was used for catalytic turnover. Mechanistic studies indicated that B.O transborylation proceeded by B.O/B.H boron exchange through a stereoretentive, concerted transition state, resembling σ-bond metathesis

Bicarbonate and alkyl carbonate radicals : structural integrity and reactions with lipid components

The authors thank EaStCHEM for funding.The elusive neutral bicarbonate radical and the carbonate radical anion form an acid/conjugate base pair. We now report experimental studies for a model of bicarbonate radical, namely methyl carbonate (methoxycarbonyloxyl) radical, complemented by DFT computations at the CAM-B3LYP level applied to the bicarbonate radical itself. Methyl carbonate radicals were generated by UV irradiation of oxime carbonate precursors. Kinetic EPR was employed to measure rate constants and Arrhenius parameters for their dissociation to CO2 and methoxyl radicals. With oleate and cholesterol lipid components methyl carbonate radicals preferentially added to their double bonds; with linoleate and linolenate substrates abstraction of the bis-allylic H-atoms competed with addition. This contrasts with the behavior of ROS such as hydroxyl radicals that selectively abstract allylic and/or bis-allylic H atoms. The thermodynamic and activation parameters for bicarbonate radical dissociation, obtained from DFT computations, predicted it would indeed have substantial lifetime in gas and nonpolar solvents. The acidity of bicarbonate radicals was also examined by DFT methods. A noteworthy linear relationship was discovered between the known pKa's of strong acids and the computed numbers of microsolvating water molecules needed to bring about their ionization. DFT computations with bicarbonate radicals, solvated with up to eight water molecules, predicted that only 5 water molecules were needed to bring about its complete ionization. On comparing with the correlation, this indicated a pKa of about -2 units. This marks the bicarbonate radical as the strongest known carboxylic acid.Peer reviewe

A revised age for the Kawakawa/Oruanui tephra, a key marker for the Last Glacial Maximum in New Zealand

The Kawakawa/Oruanui tephra (KOT) is a key chronostratigraphic marker in terrestrial and marine deposits of the New Zealand (NZ) sector of the southwest Pacific. Erupted early during the Last Glacial Maximum (LGM), the wide distribution of the KOT enables inter-regional alignment of proxy records and facilitates comparison between NZ climatic variations and those from well-dated records elsewhere. We present 22 new radiocarbon ages for the KOT from sites and materials considered optimal for dating, and apply Bayesian statistical methods via OxCal4.1.7 that incorporate stratigraphic information to develop a new age probability model for KOT. The revised calibrated age, ±2 standard deviations, for the eruption of the KOT is 25,360 ± 160 cal yr BP. The age revision provides a basis for refining marine reservoir ages for the LGM in the southwest Pacific

A Boron-Oxygen Transborylation Strategy for the Asymmetric Reduction of Ketones

The asymmetric reduction of ketones with pinacolborane (HBpin) has been catalysed by an enantioenriched borane catalyst, formed in situ from 9-borabicyclo[3.3.1]nonane (H-B-9-BBN) and β-pinene. While previously only used stoichiometrically, this borane has now been rendered catalytic using a new turnover mechanism, B-O transborylation. Thermodynamic and kinetic parameters of the key B-O/B-H transborylation showed this is a sub-class of σ-bond metathesis

A revised age for the Kawakawa/Oruanui tephra, a key marker for the Last Glacial Maximum in New Zealand

The Kawakawa/Oruanui tephra (KOT) is a key chronostratigraphic marker in terrestrial and marine deposits of the New Zealand (NZ) sector of the southwest Pacific. Erupted early during the Last Glacial Maximum (LGM), the wide distribution of the KOT enables inter-regional alignment of proxy records and facilitates comparison between NZ climatic variations and those from well-dated records elsewhere. We present 22 new radiocarbon ages for the KOT from sites and materials considered optimal for dating, and apply Bayesian statistical methods via OxCal4.1.7 that incorporate stratigraphic information to develop a new age probability model for KOT. The revised calibrated age, ±2 standard deviations, for the eruption of the KOT is 25,360 ± 160 cal yr BP. The age revision provides a basis for refining marine reservoir ages for the LGM in the southwest Pacific. © 2012