Objective The development of methods for the transition metal (TM) catalyzed functionalisation of C–H bonds has emerged as an extremely important topic in present-day organic synthesis aiming at providing tools that allow treating the ubiquitous and normally inert C–H bonds as any other functional group for synthetic modifications. However, controlling the site of C–H activation or distinguishing between the subtle differences in reactivity of two given C–H bonds is one of the major challenges yet to be addressed. In this context, meticulous design of directing groups (DG) over the last decades has enabled a variety of relatively unreactive C–H bonds to be functionalised under transition metal catalysis. To date, much progress has been made in developing strategies for the ortho-functionalisation of arenes mainly through the installation of DGs in the stoichiometric amount. However, these DGs are not part of the final target molecule; as a consequence, its covalent installation and/or removal from the substrate will add additional steps to the synthetic sequence thus lowering the efficiency and applicability of these approaches. On the other hand, distal meta- and para-C–H functionalisation approaches, are extremely scarce despite these substitutions are widespread motifs amongst biologically active molecules. The research outlined in this proposal aims at developing a process that makes use of a transient DG in a catalytic amount which binds reversibly with carbonyl compounds via imine formation leading to a novel direct meta- and para-functionalisation methodology. Precisely, we seek to develop a protocol that removes the need for the use of stoichiometric directing groups to activate distal C–H bonds. The realization of the proposed objectives will push the boundaries of the state-of-the-art in the area of remote C–H bond functionalisation by providing atom and step economical access to molecules that are difficult to prepare via conventional multi-step routes. Fields of science natural scienceschemical sciencesorganic chemistryhydrocarbonsnatural scienceschemical sciencescatalysis Keywords Transient directing group C–H bond activation meta-C–H para-C–H transition metal catalyst ligand metallacycle palladium aminoquinoline imine enamine 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-2018 - Individual Fellowships Call for proposal H2020-MSCA-IF-2018 See other projects for this call Funding Scheme MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinator THE UNIVERSITY OF MANCHESTER Net EU contribution € 224 933,76 Address OXFORD ROAD M13 9PL Manchester United Kingdom See on map Region North West (England) Greater Manchester Manchester 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 € 224 933,76