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.
Field of science
- /natural sciences/chemical sciences/organic chemistry/hydrocarbons
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