Project description DEENESFRITPL Harnessing enantioselective C-H oxidation in organic synthesis Organic compounds are characterised by multiple and diverse bonds between carbon (C) and hydrogen (H). In metabolism, these C-H bonds can be converted into functional C-O bonds in a precise manner by oxidative enzymes, producing chiral metabolites of diverse structure and function. The EU-funded ECHO-GRACADE project aims to harness the power of enantioselective C-H oxidation in synthetic chemistry in the absence of real enzymes. For this purpose, scientists will employ small molecule manganese catalysts that will function as minimalistic hydroxylases. The project will focus on the design of these catalysts as tools in organic chemical synthesis for paradigmatic asymmetric reactions that involve C–H oxidation. Show the project objective Hide the project objective Objective Chemo- and enantioselective oxidation of aliphatic C-H bonds is a cornerstone reaction in metabolism. The ubiquitous presence of multiple and diverse C-H bonds in organic molecules is used by oxidative enzymes to deliver functionality and chirality to metabolite precursors, rapidly creating product diversity. Despite its huge potential in organic synthesis, non-enzymatic enantioselective C-H oxidation of aliphatic sites remains inaccessible and has never been incorporated in synthesis. Harnessing the power of this reaction will open straightforward, yet currently inaccessible, paths in synthetic planning. However, realization of this goal requires conceptual breakthroughs in order to chemo-, regio- and stereo-selectively create a C-O bond from a non-activated alkyl C-H bond, even in the presence of a priori more reactive groups. In this project, chemo-, and site-selective asymmetric aliphatic oxidation is targeted by taking advantage of; a) stereoretentive enzyme-like metal-based C-H oxidations performed by small molecule manganese catalysts, devised as minimalistic hydroxylases, and b) polarity reversal exerted by fluorinated alcohol solvents in electron-rich functional groups, which enable chemoselective C-H hydroxylation of densely functionalized molecules. Desymmetrization via enantioselective C-H oxidation is devised as a powerful type of reaction that will create multiple chiral centers in a single step. Building on the rich chemical diversity and modular architecture of aminopyridine manganese complexes, rapid elaboration of libraries of catalysts is targeted. Rational manipulation of steric, electronic, directing effects and supramolecular substrate recognition factors guided by multiple parametrization analyses will be employed for directing evolution in catalyst design. This project will provide the catalysts and their use in paradigmatic reactions in order to establish enantioselective C-H oxidation as a reliable tool in organic synthesis. Fields of science natural scienceschemical scienceselectrochemistryelectrolysisnatural scienceschemical sciencesinorganic chemistrytransition metalsnatural scienceschemical sciencesorganic chemistryalcoholsnatural scienceschemical sciencescatalysisnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2019-ADG - ERC Advanced Grant Call for proposal ERC-2019-ADG See other projects for this call Funding Scheme ERC-ADG - Advanced Grant Host institution UNIVERSITAT DE GIRONA Net EU contribution € 2 499 387,50 Address PLACA SANT DOMENEC 3 17004 Girona Spain See on map Region Este Cataluña Girona Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 2 499 387,50 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all UNIVERSITAT DE GIRONA Spain Net EU contribution € 2 499 387,50 Address PLACA SANT DOMENEC 3 17004 Girona See on map Region Este Cataluña Girona Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 2 499 387,50