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Novel Biomimetic Organocatalysts

Final Report Summary - NBO (Novel Biomimetic Organocatalysts)

This project began by investigating the design of artificial enzymes - the catalysts present in nature which make all life possible. In trying to design these systems, we observed catalytic behaviour never seen before, which allowed us to develop a new type of catalyst for a process called the Tishchenko reaction. This is a reaction which holds much promise as a synthetic methodology, but which is notoriously difficult to control when the two reacting partners are not identical. By being able to design catalysts that we could control the properties of, we were able to circumvent many of the selectivity issues that bedevil the Tishchenko reaction, and render it a far more synthetically useful process than it perhaps was at the outset of the project.

We also developed new reactions between enolisable anhydrides and electrophiles. These reactions were known for some time, but no catalysts were available for them, meaning that efficient and (more importantly) asymmetric versions of these processes were not available. We discovered a new way of promoting these reactions using a mild form of bifunctional catalyst (one which activates the nucleophilic and electrophilic reaction components simultaneously) - which allowed the cycloaddition of enolisable anhydrides and a variety of electrophiles with excellent enantio- and diastereocontrol at operationally convenient temperatures. The products which now can be synthesised in enantioenriched form are diverse and belong to some of the most useful and medicinally relevant core units in organic/medicinal chemistry.