MOCaS

This project is to develop a sustainable synthetic methodology in line with cutting-edge themes in green chemistry such as homogeneous catalysis with earth-abundant metals and up-grade of lignocellulosic biomass. The objective is to develop eco-friendly site-selective oxidations of unprotected and mono-protected sugars into keto-sugars derivatives via an iron catalyzed transfer hydrogenation process. This atom economical methodology will give access, to either, keto-lactones (2 successive oxidations) or keto-sugars (mono-oxidation) from unprotected and C1-protected (anomeric position) sugars respectively without the need of strong oxidant, elaborate set-ups or harsh conditions. The molecules targeted in this study will be of high-interest as they are readily available from natural feedstock (biomass), compact (low-Mw) and 3D-polyfunctional molecules with potential applications in fine and medicinal chemistry. The project has been structured in 3 tasks: Task 1 will focus on the development of the catalytic system using a carefully selected family of iron catalysts known in transfer hydrogenation. Optimization of the catalytic system for the selective oxidation of a hydroxyl group will be carried out on both sugar lactones (obtained from unprotected sugars oxidation) and C1-protected sugars. Studying these two types of substrates in parallel will allow to understand several key-features of the transformation (electronic effects, stereochemistry and geometry of the substrate), and supply alternative substrates for a greater molecular diversity. Moreover, employing 6- and 5-membered ring substrates (pyranose and furanose) will give access to complementary structures, since some positions will not be available for oxidation depending on the cycle size. The use of additives such as boron derivatives known for reversible ‘masking’ of sugars and/or activating groups, will also be investigated to promote efficient and selective oxidations. Task 2 will focus on the formal hydrogen acceptor of the reaction with two main objectives: (i) decrease the stoichiometry of the acceptor required for an overall improved atom-efficiency, without compromising the efficacy (equilibrium shift) of the transformation and (ii) increase the synthetic applicability of our approach by allowing the concomitant upgrade of both donor (carbohydrates) and acceptor (carbonyl derivatives) in the process. At the end of this milestone, a one-pot successive oxidations of unprotected sugars to keto-lactones will be optimised and scaled-up with the best acceptors. Task 3 will be an application of the oxidation methodology developed in Task 1 & 2. Our objectives will be to implement the redox system developed in a hydrogen borrowing cascade employing imine intermediates to access higher-value products such as amino-polyols from C1-protected sugars. This proposal, submitted by a recently appointed lecturer in the URCOM laboratory, is in rupture with the traditional research topics in the research unit. However, this project is perfectly aligned with the willingness of the laboratory to re-orientate its research efforts toward the development of more eco-designed (eco-friendly and economical) chemical methodologies using natural resources available in Normandy region (circular economy) and their applications in healthcare and cosmetics.