Catalytic Enantioselective Lewis Base Chemistry: Solving the turnover problem

The drive to reduce the environmental impact of the chemical sciences requires the development of efficient catalytic enantioselective methodologies to prepare enantiomerically pure compounds. Within this arena, the selective preparation of bespoke nitrogen heterocycles (such as indolines) is of widespread academic and industrial importance due to their privileged place as bioactive molecules and scaffolds for drug discovery. This project aims to develop versatile and state-of-the-art methodologies for the catalytic enantioselective synthesis of indolines and their derivatives using isothioureas as organocatalysts.
Background: We have previously shown that isothioureas promote a range of one-pot catalytic enantioselective cascade processes that rely upon the formation of a reactive ammonium enolate from readily available carboxylic acids. Although versatile, one drawback of this approach is that catalyst regeneration and turnover is promoted by intramolecular cyclisation (such as lactonisation). Building upon this work, this project will extend this process to the enantioselective cyclisation of readily prepared ester-aldimine substrates that will use an external nucleophilic source to promote catalytic turnover. This will solve the general problem of "external" catalytic turnover in Lewis base catalysis.







Please list any agreed training requirement

Calum will receive extensive training in catalysis and in particular enantioselective catalytic processes. This will cover synthesis and characterisation of new materials, as well as extensive mechanistic and kinetic analysis.