Discovery of photocatalytic reactions enabled by high-throughput experimentation

The discovery of photocatalysed reactions involving many different substrate classes has significantly expanded accessible chemical space. However, the rational design of new classes of photocatalytic reactions can be hindered by their mechanistic complexity. A high-throughput experimentation approach was harnessed to facilitate the discovery of photocatalytic reactions involving novel pairs of substrate classes. The approach enabled the discovery of an unprecedented dearomative [4+3] photocycloaddition-oxidation reaction, and the extension of a [2+2] photocycloaddition to new classes of alkene substrate. The [4+3] photocycloaddition-oxidation was optimised, and shown to enable the synthesis of many complex bridged scaffolds from imidazo[1,2-a]pyrimidines and alternative aromatic substrates. High-throughput experimentation may be a useful tool for discovering other synthetically useful transformations that are based on rich and underexplored photocatalysis reactivity.