Ligand-Free Suzuki-Miyaura Coupling with Sulfur-Modified Gold-Supported Palladium in the Synthesis of a Conformationally-Restricted Cyclopropane Compound Library with Three-Dimensional Diversity

A conformationally restricted privileged structure library with stereo chemical diversity for a fragment growth methodology comprising 90 compounds was designed and systematically and efficiently synthesized using sulfurmodified Au-supported Pd (SAPd)-catalyzed ligand-free Suzuki-Miyaura coupling of vinyl iodide promoted by microwave and subsequent amidation in liquid-phase combinatorial chemistry as key reactions. Evaluation of the compounds with a 20-kinase panel indicated the usefulness of this fragment growth methodology for finding hit library compounds for fragment-based drug discovery.