New Strategies for the Synthesis of Medicinally Relevant Small Molecules

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The desire to efficiently and safely prepare value-added organic molecules from simple building blocks remains a key driving force in the chemical industry and has shaped the field of organic synthesis in recent decades. The transformation of chemical building blocks into medicines or fine chemicals typically requires numerous synthetic steps, leading to an increase in manufacturing costs and the production of chemical waste. The reagents used in these transformations and the waste that is generated may also be toxic or corrosive, leading to additional complications for reaction set-up, waste disposal and product purification. My research program focuses on developing enabling synthetic methods to access medicinally relevant small molecules in a more efficient (e.g. less waste, fewer steps) and/or safer (e.g. non-toxic reagents/waste) manner. In particular, our recent efforts have focused on the development of new methods to prepare and functionalize cyclopropane- and nitrile-containing molecules given the importance of these substrate classes in the pharmaceutical and agrochemical industries. The research that will be proposed in this NSERC Discovery Grant application will focus on using the expertise we have gained over the last 5 years to develop new enabling technologies for synthetic organic chemists. We will maximize impact on our recent discoveries in the area of Ni-catalysis involving 1-electron chemistry to develop 1) a broad scope of reductive cyanation reactions and 2) cross-coupling reactions involving C(sp3)-O electrophiles. Furthermore, as pioneers of the use of electrophilic homoenolates, we will exploit these reagents for the synthesis of small 3- and 4-membered rings. Throughout this program, we will focus on target selection, to ensure we are preparing molecules of high interest to research end-users (e.g. industrial chemists), and mechanistic studies, to enable new catalyst/reagent design and the exploration of new chemical reactivity.