Remote site-selective C–H activation directed by a catalytic bifunctional template

• Published in: Nature (London) 2017-03, Vol.543 (7646), p.538-542
• Main Authors: Zhang, Zhipeng, Tanaka, Keita, Yu, Jin-Quan
• Format: Article
• Language: English
• Subjects: 639/638/403/933; 639/638/403/934; Alkenes - chemistry; Carbon; Carbon - chemistry; Catalysis; Chemical bonds; Chemical synthesis; Chemistry Techniques, Synthetic - methods; Humanities and Social Sciences; Hydrogen; Hydrogen - chemistry; letter; Ligands; Metals - chemistry; multidisciplinary; Nitriles - chemistry; Pyridines - chemistry; Quinolines - chemistry; Science; Substrate Specificity; Substrates
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature21418

A method is described for selectively activating remote C–H bonds in heterocycles by using a catalytic template that binds by reversible coordination instead of a covalent linkage, removing the need for specific functional groups on which to attach the template. C–H activation using a reversible template One way to reduce the number of steps in a chemical synthesis is to use C–H activation, in which reactions are directed to specific carbons without needing to have a functional group attached to that carbon. But organic molecules contain many C–H bonds so, to ensure that only one is activated, directing protocols with removable templates have been developed. Jin-Quan Yu and colleagues expand on this idea to enable remote C–H activation of 3-phenylpyridines using a directing template that is temporarily attached through reversible metal–ligand bonds. This methodology means that C–H activation of more remote bonds can be achieved, and the number of steps can be reduced, because the reversibility of the attachment means that the template does not need to be attached and removed in separate steps. In chemical syntheses, the activation of carbon–hydrogen (C–H) bonds converts them directly into carbon–carbon or carbon–heteroatom bonds without requiring any prior functionalization. C–H activation can thus substantially reduce the number of steps involved in a synthesis. A single specific C–H bond in a substrate can be activated by using a ‘directing’ (usually a functional) group to obtain the desired product selectively 1 , 2 , 3 , 4 , 5 . The applicability of such a C–H activation reaction can be severely curtailed by the distance of the C–H bond in question from the directing group, and by the shape of the substrate, but several approaches have been developed to overcome these limitations 6 , 7 , 8 , 9 , 10 , 11 , 12 . In one such approach, an understanding of the distal and geometric relationships between the functional groups and C–H bonds of a substrate has been exploited to achieve meta -selective C–H activation by using a covalently attached, U-shaped template 13 , 14 , 15 , 16 , 17 . However, stoichiometric installation of this template has not been feasible in the absence of an appropriate functional group on which to attach it. Here we report the design of a catalytic, bifunctional nitrile template that binds a heterocyclic substrate via a reversible coordination instead of a covalent linkage. The two metal centres coordinated to this template have diff