Grant: Discovery Grants Program - Individual

Most pharmaceuticals that treat disease and improve our quality of life have emerged from intense medicinal chemistry efforts. Drugs evolve from iterative testing of thousands of molecules, each of which has been designed and synthesized in an average of 8 steps! Chemical innovation is at the core of this endeavour, and new technologies are rapidly adopted to accelerate the drug discovery process. Our program is centred on the development of new reactions, reagents and catalysts for the synthesis of key structural subunits containing nitrogen atoms, which are present in >95% of drug candidates. Ultimately, this research will allow to prepare biologically-active molecules more efficiently, and enables the formation of new compounds for drug development. Such efforts are also important from a Green Chemistry perspective, as efficient reactions inherently minimize the generation of "chemical waste", which remains an important issue associated with pharmaceuticals. The reactions targeted in this research are divided in three themes. In the first theme we will develop new reactions to form nitrogen-containing molecules This includes work on alkene hydroamination, using a new approach relying only on changes in oxidation state of the reagents and products occurring under the reaction conditions. This requires the development of "surgically" precise redox procedures to enable difficult reactions forming useful heterocycles and amines. Our work with masked isocyanates will focus on difficult reactions forming carbon-carbon bonds, allowing the synthesis of cyclic and acyclic molecules possessing an NCO subunit. In the second theme we will develop new reagents, which can greatly facilitate the assembly of complex structures. Specifically, we will develop a new linchpin, a building block type reagents that can be selectively functionalized in two directions. The first amide linchpin reagent will provide access to many valuable molecules possessing the NCO subunit. We will also develop O-borylhydroxylamines, to establish new cyclo-addition reactions forming complex heterocycles. The third overarching theme will pursue high risk/high reward opportunities derived from the work above, aiming for longer term impact. This include achieving a truly catalytic borrowing oxygen process and developing reactions that will form single enantiomers of useful products using approaches developed during this research. Overall, this research will result in new reactions, reagents and catalysts, in the development of new concepts, and will provide new approaches to compounds that are currently difficult to synthesize. As part of this research, trainees will be immersed in a supportive, inclusive and respectful environment as they acquire many skills, including communication, interpersonal skills and leadership. A diverse group of trainees will acquire skills that are ideally suited for future work in industry (e.g. pharmaceuticals), government or academia.