Development of asymmetric methods using an experimental-computational strategy

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The goal of the proposed research is to develop simple and efficient asymmetric methodologies of broad use that will serve as tools to facilitate the work of synthetic chemists in both academia and industry. Achieving this feat is a continuing challenge since both reactivity and stereoselectivity must be optimized concurrently. This work is of the utmost importance since chiral molecules can possess useful properties and have numerous applications. For example, a large number of modern drugs are chiral enantiopure compounds. Efficiency and cost are important related aspects of the research process, and it is critical to employ all the tools available to streamline and enhance its productivity. My approach will focus on a strong interaction between experimental and computational studies to achieve progress at lower cost and in reduced time. Molecular modelling is particularly well suited to understand the stereoselectivity and rationalize the design of the chirality-inducing moiety. My first research theme focuses on the synthesis and investigation of catalysts based on a new class of anionic carbene ligands derived from the N-iminoimidazolium ylide motif. These compounds will be obtained through a simple and modular synthetic route, which will rapidly lead to the creation of libraries of complexes that will facilitate the investigation of their potential. This diversity is also crucial to enable the fine tuning of the metal complexes reactivity for specific methodologies. A first generation of chiral catalysts will be synthesized and evaluated in model reactions (e.g. allylic alkylations, 1,4-conjugate additions). My second research theme consists of the development of novel chiral iodine(III) reagents that will be used in enantioselective iodine(III) mediated reactions, such as the alpha-tosyloxylation of ketones and ditosyloxylation of styrene. My last theme targets the study of Lewis base-mediated enantioselective iodocyclization reactions. Computational chemistry will be used to understand the mechanism of these reactions, and help design new chiral bases.