Palladium- and Copper-Catalyzed Solution Phase Synthesis of a.pdf

J. Comb. Chem. 2009, 11, 1061–1065 1061 Palladium- and Copper-Catalyzed Solution Phase Synthesis of a Diverse Library of Isoquinolines Sudipta Roy,† Sujata Roy,† Benjamin Neuenswander,‡ David Hill,‡ and Richard C. Larock*,† Department of Chemistry, Iowa State Uni Versity, Ames, Iowa 50011, and The UniVersity of Kansas NIH Center of Excellence in Chemical Methodologies and Library DeVelopment, Lawrence, Kansas 66047 Recei Ved June 26, 2009 The solution-phase synthesis of a 111 member isoquinoline library is described. The isoquinoline scaffold has been accessed through the palladium- and copper-catalyzed cyclization of iminoalkynes and the palladium- catalyzed iminoannulation of internal alkynes, followed by diversification of hydroxyl functionality where it is present. Introduction allowing one to dramatically increase molecular complexity The isoquinoline nucleus is one of the most abundant in just a few synthetic steps starting from commercially available materials. In a continuation of our research efforts structural motifs found in natural products and biologically active molecules.1 Isoquinoline derivatives exhibit a broad to adapt heterocyclization chemistry to a high-throughput range of pharmacological activity, including antitumor, synthesis format,15 we herein report the first solution-phase antifungal, antimalarial, antihypertensive and antihistam