Project Summary – Iodine Catalyzed Cross-Coupling Reactions The proposed research aims to discover and develop economical, environmentally- and user-friendly iodine catalyzed cross-coupling reactions for the synthesis of key chemical bonds (carbon-nitrogen and carbon- carbon bonds), functional groups (amides, imides and ketones) and frameworks (nitrogen-containing heterocycles such as pyrrole). Despite the great interest and efforts devoted in cross-coupling reactions, examples of iodine catalyzed cross-coupling still remain scarce compared to the number of protocols mediated by transition metal catalysts. The proposal is grounded in our preliminary results that acyl radical species are readily generated from aldehyde substrates in the presence of an iodine/potassium persulfate catalyst system, which participate in coupling reactions with a variety of chemical compounds containing nitrogen nucleophiles. Upon the completion of the proposed work, three specific aims will be accomplished: 1) a facile iodine catalyzed carbon-nitrogen bond formation protocol for the preparation of amides and imides will be developed; 2) an iodine catalyzed carbon-carbon bond formation reaction via radical addition mechanism will be developed; 3) a carbon-carbon bond formation reaction via an iodine and first-row late transition metal co- catalyzed cross-coupling mechanism will be developed. The new methods are expected to serve the critical needs of synthetic and medicinal chemists in preparation of the corresponding chemical bonds and frameworks for novel therapeutics. A thorough investigation of the proposed iodine catalysis mechanism will be conducted, which is expected to yield a comprehensive understanding of the proposed iodine catalysis and serve as a template for future study in the field. In addition, the proposal will improve and strengthen the infrastructure of research and education at Queens College. It will not only provide research opportunities to the many underrepresented minority students among the Queens College undergraduates, but also will help nurture the young generation of scientists who are interested in pursuing a research career in the STEM disciplines.

Project Narrative – Iodine Catalyzed Cross-Coupling Reactions The proposal aims at developing the mechanism for green synthetic protocols of a few key chemical bonds, functional groups, and frameworks prevalently appearing in modern drug molecules. It focuses on the study of coupling reactions for carbon-carbon and carbon-nitrogen bond formations. The proposed iodine-catalyzed cross-couplings have obvious advantages over the transition metal-catalyzed coupling protocols widely employed in the drug molecule synthesis for using an inexpensive green catalyst and effectively avoiding toxic metal catalyst residues in final drug molecules. The new methods are expected to serve the critical need for medicinal chemists in the course of preparing the corresponding chemical bonds and frameworks for novel therapeutics.