Mechanism of Asymmetric Organocatalysis by Planar Chiral Pyridines of the Addition of Nucleophiles to Ketenes

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The development of small non-metal organocatalysts is becoming increasingly important given the frequent high cost of purchase and disposal of metal-analogues. As a result the development of small molecule organocatalysts including chiral Bronsted acids for asymmetric synthesis has gained considerable attention over the past five years. Asymmetric catalysis by Bronsted acid catalysts is presumed to involve proton transfer between catalyst and substrate, however the mechanism has not been rigorously probed thus far. To date, the success of a given Bronsted catalyst is highly substrate and solvent dependent and few broadly successful catalysts exist. There remains ample scope for optimisation of existing catalysts and design of new better catalysts, which is unachievable without a better mechanistic understanding. This research proposal will address several key mechanistic questions about Bronsted acid organocatalysis using solution kinetics and structure-activity approaches.Physical-organic chemistry/the application of quantitative tools taken (historically) from physical chemistry to the solution of problems in mechanisms or in understanding properties-originated and flourished in the UK for several decades. However it is now recognized that in the last twenty years POC has fallen out of step with developments in synthetic chemistry. The present proposal represents an ideal case where detailed POC kinetic and structure-activity studies can be conducted at the crucial early stages of catalyst development.