The goal of this proposal is development of a new approach for directed ortho-metalation (DoM) chemistry, highlighting the use of "promoted" hydrocarbon media to provide safe, green, atom-economical procedures. Hydrocarbon media do not suffer from the issues that often negate the use of ethereal media for larger scale preparations, but must be "promoted", i.e., treated with small increments of ethers, TMEDA, etc, to activate alkyllithiums. However, this requirement may be exploited to synthetic advantage, allowing a much wider range of promoter/conditions combinations and thereby enabling such metalating systems to become tailor-made. Specific aims of this investigation are to further the utility of hydrocarbon media for DoM chemistry by studying directing metalation groups/electronic factors involved in ortho-lithiation, exploring distinct media considerations for final derivatization reactions, and applying new findings to novel high-yield syntheses of target compounds.
With the support of this Research at Undergraduate Institutions award from the Organic and Macromolecular Chemistry Program, Professor Donald W. Slocum, of the Department of Chemistry at Western Kentucky University, is studying new ways to introduce reactive carbon-metal bonds into organic molecules. The products of these "metalation" reactions can serve as versatile intermediates in the synthesis of more complex molecules of interest in the pharmaceutical, biotechnology, nanotechnology, polymer and specialty chemical sectors. Professor Slocum and his students are developing promoters, allowing metalation reactions to be carried out in simple hydrocarbon media in place of more hazardous solvents. Through the development of efficient procedures, with high atom economy and using environmentally benign solvents, these studies are advancing the principles of green chemistry.
