EnCHAANT · Enantioselective Catalytic Hydrogen Atom Abstraction through Nitrogen-centred Transfer - Development and Exploration

Chemical reactions, broadly speaking, can be mechanistically classified into two distinct types – those in which the electrons move singly and those in which they move in pairs, referred to as ‘radical reactions’ and ‘ionic reactions’ respectively. The remarkable volume of attention now being focused on radical reactions, due to the popularisation of photoredox catalysis, underscores a long-standing challenge within the field of radical chemistry – that of controlling enantioselectivity. This proposal will develop new catalysts that will perform a key mechanistic process in radical chemistry, hydrogen atom transfer, in an enantioselective manner. Specifically it will control asymmetry in the abstraction of hydrogen atoms. The proposal builds on very recent exciting results from the host group and will seek firstly to develop a process for catalytic deracemization and diols and amino alcohols, important chiral building blocks for synthetic chemistry and a range of applications. The second key goal will be to fundamentally modify the chiral scaffold used in the previous work, one that is based on the cinchona alkaloid natural products. Inspired by a recent paper showing DABCOnium salts to be more powerful hydrogen atom abstractors we will synthesise de novo DABCO analogues of the cinhona alkaloids using a route that has been developed, for other purposes, in the host group. The resulting catalysts should dramatically expand the scope of the process and have a large impact in the field of enantioselective radical chemistry. Finally, the combined insights from the main WPs will be used to enable late stage 'stereochemical editing' of complex pharmaceuticals, allowing one enantiomer to be converted to the other at will.