Combinatorial libraries and the development of organic synthetic methods. PLS modelling to discriminate between successful and failed reaction systems

The paper describes a combinatorial study in which substrate structure, Lewis acid properties, and solvent properties were varied to explore the Fischer indole synthesis. The number of items in the combinatorial library was 254. Of these, 162 afforded the Fischer reaction. It is shown how PLS modelling can be used to identify critical properties of the reaction systems so that both conditions that are favourable for the reaction as well as conditions that fail can be identified. Transformation of the PLS models to response surface models makes it possible to analyse the properties of the reaction system in detail.