A strategy for generating diverse collections of small molecules has been developed that features a multicomponent assembly process (MCAP) to efficiently construct a variety of intermediates possessing an aryl aminomethyl subunit. These key compounds are then transformed via selective ring-forming reactions into heterocyclic scaffolds, each of which possesses suitable functional handles for further derivatizations and palladium-catalyzed cross coupling reactions. The modular nature of this approach enables the facile construction of libraries of polycyclic compounds bearing a broad range of substituents and substitution patterns for biological evaluation. Screening of several compound libraries thus produced has revealed a large subset of compounds that exhibit a broad spectrum of medicinally-relevant activities.