Identifying lead hits in catalyst discovery by screening and deconvoluting complex mixtures of catalyst components.

A reaction-economic combinatorial strategy is described for lead hit identification in catalyst discovery efforts directed towards a specific transformation. Complex mixtures of rationally chosen precatalysts and ligands are screened against various reaction parameters to identify lead conditions in a small number of reactions. Iterative deconvolution of the resulting hits identifies which components contribute to the lead generated catalyst. Application of this strategy rapidly uncovered a new mild generated catalyst for the dehydrative Friedel-Crafts reaction as well as conditions for selective monoarylation in catalytic -C-H arylation of unsubstituted -(quinolin-8-yl)benzamide.