Project description DEENESFRITPL Moving beyond enantioselectivity in fluorination reactions Fluorine is a central element in the pharmaceutical and agricultural industries as a result of its unique features as a substituent. While past research efforts have placed a heavy focus on achieving high levels of enantioselectivity (that is, the ratio of a compound to its mirror image) in fluorination reactions, other types of selectivity (chemoselectivity, diastereoselectivity, site selectivity, regioselectivity) are of equal importance and represent further challenges in the field. The EU-funded project REGIOFLU addresses these other types of selectivity in the context of fluorination reactions. By bridging this gap, scientists hope to develop a more unified strategy to solving broader selectivity challenges in organic synthesis, which would translate to a more diverse set of imaging tools for biological studies and a better handle for diagnostics in the clinic. Show the project objective Hide the project objective Objective The challenge of performing reactions with catalyst control over regioselectivity has not been met with a general solution. Here, we approach this longstanding problem in the field by addressing the specific question of how to regioselectively install fluorine - a key element in the agrochemical and pharmaceutical industries. By combining the charge-modulating properties of hydrogen bond donors with a phase transfer event, we propose that it will be possible to use simple fluoride salts in regioselective fluorination reactions. Using hydrogen bonding as an activation mode for cheap inorganic salts, we will address new challenges in site selectivity through catalyst design and an extensive interrogation of the potential energy landscape of the reactions. This research will demand catalysts that can control the charge density on a nucleophile and will require computational studies that enable the prediction of regioselectivity on the basis of a nucleophilicity index. To apply the lessons of these studies in the context of asymmetric catalysis, new high performance catalysts will be developed that are capable of kinetic resolution and enantioconvergent allylic fluorination. The ultimate test of the regioselective fluorination methods will be in the synthesis of novel PET tracers, where both time and operational simplicity are critical to achieving a high specific activity. Regioselective hydrogen bonding phase transfer catalysis will strongly influence the broader landscape of catalysis and yield mechanistic insight into a novel synthetic process while providing valuable biological probes from abundant feedstock chemicals. The interdisciplinary aim of this proposal is to connect computational chemists, synthetic organic chemists, radiochemists, and PET imaging specialists in a framework that allows the production of new tools to expedite clinical breakthroughs. Fields of science medical and health sciencesclinical medicineradiologynuclear medicinenatural scienceschemical sciencesinorganic chemistryhalogensnatural scienceschemical sciencescatalysis Keywords Hydrogen Bonding Catalysis Phase Transfer Catalysis Regioselective Catalysis Feedstock Reagents Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2019 - Individual Fellowships Call for proposal H2020-MSCA-IF-2019 See other projects for this call Funding Scheme MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinator THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD Net EU contribution € 212 933,76 Address Wellington square university offices OX1 2JD Oxford United Kingdom See on map Region South East (England) Berkshire, Buckinghamshire and Oxfordshire Oxfordshire 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 Other funding € 0,00
