Catalytic Photoredox Approaches to Reactive Intermediates

Abstract

Photoredox catalysis is a rapidly evolving field enabling chemists to design novel methods for chemical synthesis, under mild and benign conditions. The application of radical chemistry has been hampered by the undesirable reagents/conditions required and has been associated with a lack of selectivity. Photoredox catalysis allows for mild radical initiation, causing enhanced control over the reaction outcome.

In chapter one we discuss the application of this new field for the design of novel chemical transformations. We then analyse the many approaches that have been made for the generation of acyl radicals, a desirable reactive intermediate due to its innate nucleophilicity.

In chapter two, we describe the development of a new photoredox catalysed method for the indirect generation of acyl radicals. A series of intramolecular cyclisation reactions were used to test this methodology. A novel cascade reaction was developed as an extension of this chemistry. Limitations of this protocol are then addressed by designing a complementary method.

Chapter three details the application of this method to target-oriented synthesis. To display synthetic practicability, we showed that our radical precursors are tolerant to a wide range of reaction conditions. We then utilise this new method to synthesise a pharmaceutical agent and detail our efforts towards the synthesis of a complex natural product.

The final chapter depicts our efforts for the enantioselective synthesis of (–)-solanacol and solanacyl acetate, two members of the strigolactone family. The core was accessed as a single stereoisomer utilising a Noyori asymmetric transfer hydrogenation. Oxidative conditions were screened to install a requisite hydroxyl unit. The mild conditions offered by photoredox catalysis proved crucial in delivering the desired regioisomer. A Trost asymmetric allylic alkylation gave (–)-solanacol as a single stereoisomer.