Experimental-Computational Synergy to Create and Understand New Synthetic Methodologies

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Modern societies are facing a number of challenges and some can only be tackled by the development of new and innovative organic synthetic processes. Accessing new molecules of biological interest is essential to the development of new therapeutic treatments eagerly needed to support the wellbeing of the aging populations. For example, the synthesis of new antibiotic drugs is of the utmost importance to stem the emergence of drug-resistant pathogens. In the context of global energy crisis and environmental challenges, the development of synthetic methods with lower environmental impact is crucial to meet our goals of sustainable development. My research program proposes to develop new synthetic methods to access organic molecules of interest at reduced environmental cost. My group has a unique expertise in both experimental and computational chemistry. My group is thus able to accelerate the research process by exploiting molecular modeling to guide the more costly experimental work. I identified two areas of research that will contribute to develop new synthetic methods meeting our goals: 1) Iodine(III)-mediated Chemistry; 2) Organometallic Catalysis. Iodine(III)-mediated Chemistry. Oxidative transformations are key synthetic methods as they enable rapid increase in molecular complexity. The development of iodine(III)-mediated processes has been particularly interesting in this regard. Iodine(III) reagents tend to be eco-friendly, being carbon-based and usually biodegradable, and have been found to be in numerous cases a good alternative to toxic heavy metal-based reagents. One challenging area of research in iodine(III) chemistry is the development of stereoselective methods. We will capitalize on our unique experimental/computational expertise to unearth the key requirements to obtain high stereoinduction in these reactions. We will also investigate new oxidative ring contraction transformations to access chiral non racemic polysubstituted butyrolactones. Finally, we will extend our work to understand and exploit the Lewis acidity of iodine(III) reagents. Organometallic Catalysis. The field has revolutionized synthetic chemistry in the past 50 years. To create an efficient catalyst, a balance between its stability and reactivity must be achieved. These properties are largely controlled by the ligands on the complex. The synthesis of new types of ligands thus enables the creation of catalysts having new properties. I will capitalize on our recent development of new families of ylide-based ligands to improve useful synthetic methodologies. In particular, we will assess their potential as functional ligands in cooperative catalysis. In this context, we will investigate borrowing hydrogen catalysis to perform C-N and C-C coupling reactions. The unique nature of the ligands we developed are expected to yield improved reactivity profiles in these transformations.