Development and Understanding of Synthetic Methodologies Using an Experimental-Computational Strategy

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The goal of this research program is oriented toward the development of efficient synthetic methodologies with low environmental impact. In particular, we want to achieve significant contributions in the field of stereoselective synthetic chemistry. This is a domain of great interest with the growing need to obtain compounds bearing one or multiple stereogenic centers with high selectivities. Accomplishing this feat is audacious since both reactivity and selectivity must be optimized concurrently. The main challenge is to comprehend the stereoinduction process in order to attain high stereoselectivities. Our approach relies on a strong interaction between experimental and computational studies to acquire this type of information in the most efficient manner. Molecular modeling is particularly well suited to understand these processes. By achieving a synergy between computational and experimental studies, we will be able to rapidly obtain mechanistic insights to accelerate the research process.* *At the experimental level, the program focuses on the development of useful synthetic methods with broad applicability. Consequently, this program is divided in two distinct research projects: 1. Development of synthetic methods based on hypervalent iodine chemistry; 2. Development of new ligands and applications in organometallic catalysis. Ultimately, these tools will serve to devise better strategies for the synthesis of complex molecules. It will facilitate the work of chemists in both academia and industry. In terms of applications, these methods will be used for example for the synthesis of new bioactive compounds (e.g. antibiotics, insecticides, anti-cancer agents) or functional materials.**Our first research theme targets the development of stereoselective iodine(III)-mediated processes. Hypervalent iodine reagents are of interest as they are polyvalent electrophiles and mild oxidants. They are a great alternative to toxic transition metals often used to perform similar transformations. We will construct upon the expertise and mechanistic insights that we gained in the last 4 years in this field, to move into higher impact research. This will be accomplished by exploring new synthetic transformations on two fronts: a) Study of enol analogs for the synthesis of chiral alpha-functionalized carbonyl compounds; b) Study of new reagents and substrates in iodine(III)-chemistry. To facilitate this development, we will undertake computational studies in parallel to better understand the reaction pathways of such reagents and substrates.**Our second research theme will focus on the synthesis and investigation of ligands as well as catalysts based on these ligands built from the N-iminoimidazolium ylide motif. The divergent retrosynthetic disconnections and modularity are the key features of these ligand precursors. This diversity is crucial as it will enable the rapid synthesis of libraries of ligand precursors. It will greatly facilitate the fine tuning of the metal complexes reactivity. Our current work focuses on the development of synthetic methods to access these compounds. We will now move toward applications in catalysis. We will first finalize the development of two new families of these ligands to consolidate the potential of library creation. Concurrently, we will evaluate the achiral complexes as catalysts in key oxidative synthetic transformations and develop simple synthetic routes to access chiral versions of these ligands. Ultimately, we will move forward to exploit the chiral ligands for the creation of chiral catalysts used in stereoselective oxidative synthetic transformations. The development of this broad class of ligands will contribute greatly to the expansion of available catalytic synthetic methods.