New systems for catalytic asymmetric epoxidation

This thesis describes the catalytic asymmetric epoxidation of olefins mediated by oxaziridinium salts. The introduction highlights some of the most successful methods for preparing chiral oxiranes and hints at the synthetic utility of this versatile molecule. The second chapter is dedicated to our efforts to synthesize chiral iminium salts as catalysts for asymmetric epoxidation. The first part of this chapter describes previous Page group findings and leads on to the current author's efforts in this area. Initial results from modified amino acids, cyclo-condensed to form dihydroisoquinolinium salts, showed that an aromatic unit at C4 of our catalysts was vital for asymmetric induction. Following this, several catalysts substituted at the 4-position of the aromatic functionality were tested, and found to be effective mediators for asymmetric epoxidation. Triphenylethylene was epoxidized with up to 71% ee when using oxone as the stochieometric oxidant. [Continues.

Continuous flow ozonolysis using atmospheric plasma

Ozonolysis is widely used in organic synthesis to obtain aldehydes and ketones from alkenes, a process of great interest, for example, for the pharmaceutical industry. This reaction is more environmentally accepted than other alternative oxidations and it has good atom efficiency. Ozonolysis, however, has an important drawback; the ozonides generated as intermediates in the process are unstable and pose a risk of explosion. To minimize this risk, continuous flow processing can be used, as this eliminates the accumulation of large amounts of hazardous intermediates, thereby offering an alternative to batch processing that greatly enhances the control and safety of the ozonolysis process.1,2 Here we report on the results obtained with an air plasma-driven continuous-flow ozonolysis system. (... continues

Observations on the Modified Wenker Synthesis of Aziridines and the Development of a Biphasic System

A cheap and reliable process for the modified Wenker cyclization to afford aziridines has been achieved using biphasic conditions for a range of amino alcohol starting materials. A 100 mmol “one-pot” process has also been devised, and the enantiopurity of the starting amino alcohol is retained in the aziridine product

“Copper-in-Charcoal” Revisited: Delineating the Nature of the Copper Species and Its Role in Catalysis

“Copper-in-charcoal” has been shown to be a versatile catalytic source of supported copper for a variety of important synthetic transformations, as well as in other fields such as energy. We herein report the characterization of this material and the implications that its preparation has on catalysis, thus providing a greater understanding of the scope and limitations of this catalyst system

Controlling the Assembly of C2-Symmetric Molecular Tectons Using a Thiocarbamate Appended Carbocyclic Cleft Molecule Analogous to Tröger’s Base

By way of appending the C₂-symmetric carbocyclic cleft diol with thiocarbamates with varying substituents, significant control of the hydrogen bonded network can be achieved. Smaller alkyl substituents lead to the formation of stacked columns of components with the apex of one molecule suitably aligned in the cleft of a second. Aryl substituents, however, lead to the formation of ribbons via an H-bonding network. Additionally, the packing of these ribbons into networks is considerably different between the enantiopure and racemic clefts, with the latter giving rise to channels within the crystal structure

Phosphino-Triazole Ligands for Palladium-Catalysed Cross-Coupling

<div>Twelve 1,5-disubtituted and fourteen 5-substituted 1,2,3-triazole derivatives bearing diaryl or dialkyl phosphines at the 5-position were synthesised and used as ligands for palladium-catalysed Suzuki-Miyaura cross-coupling reactions. Bulky substrates were tested, and lead-like product formation was demonstrated. The online tool SambVca 2.0 was used to assess steric parameters of ligands and preliminary buried volume determination using XRD obtained data in a small number of cases proved to be informative. Two modelling approaches were compared for the determination of</div><div>the buried volume of ligands where XRD data was not available. An approach with imposed steric restrictions was found to be superior in leading to buried volume determinations that closely correlate with observed reaction conversions. The online tool LLAMA was used to determine lead-likeness of potential Suzuki-Miyaura cross-coupling products, from which ten of the most lead-like were successfully synthesised. Thus, confirming these readily accessible triazole-containing phosphines as highly suitable ligands for reaction screening and optimisation in drug discovery campaigns.</div

Simultaneous Clicknetic Resolution Coetaneous catalytic kinetic resolution of alkynes and azides through asymmetric triazole formation

A non-enzymatic simultaneous kinetic resolution of racemic alkynes and racemic azides utilising an asymmetric CuAAC reaction is reported. The use of a CuCl (R,R)Ph-Pybox catalyst system effects a simultaneous kinetic resolution of two racemic starting materials to give one major triazolic diasteroisomer in the ratio 74:12:4:10 (dr 84:16, 90% ee maj). The corresponding control reaction using an achiral copper catalyst gives the four possible diastereoisomers in a 23:27:23:27 ratio, demonstrating minimal inherent substrate control.<br

Kinetic Resolution in Asymmetric Epoxidation using Iminium Salt Catalysis

The first reported examples of kinetic resolution in epoxidation reactions using iminium salt catalysis are described, providing up to 99% ee in the epoxidation of racemic <i>cis</i>-chromenes

Asymmetric Epoxidation Using Iminium Salt Organocatalysts Featuring Dynamically Controlled Atropoisomerism

Introduction of a pseudoaxial substituent at a stereogenic center adjacent to the nitrogen atom in binaphthyl- and biphenyl-derived azepinium salt organocatalysts affords improved enantioselectivities and yields in the epoxidation of unfunctionalized alkenes. In the biphenyl-derived catalysts, the atropoisomerism at the biphenyl axis is controlled by the interaction of this substituent with the chiral substituent at nitrogen

Asymmetric Epoxidation Using Iminium Salt Organocatalysts Featuring Dynamically Controlled Atropoisomerism

Introduction of a pseudoaxial substituent at a stereogenic center adjacent to the nitrogen atom in binaphthyl- and biphenyl-derived azepinium salt organocatalysts affords improved enantioselectivities and yields in the epoxidation of unfunctionalized alkenes. In the biphenyl-derived catalysts, the atropoisomerism at the biphenyl axis is controlled by the interaction of this substituent with the chiral substituent at nitrogen