Charge-controlled Pd catalysis enables the meta-C–H activation and olefination of arenes Arup Mondal 1 , Marina Díaz-Ruiz 2,+ , Fritz Deufel 3,+ , Feliu Maseras 2, * and Manuel van Gemmeren 1,3, * 1 Organisch-Chemisches Institut, WWU Münster, Münster, Germany, 2 Institute of Chemical Research of Catalonia, Tarragona, Spain, 3 Otto-Diels-Institut für Organische Chemie, CAU, Kiel, Germany + equal contribution, *corresponding author The few approaches for meta -selective arene C–H activation and subsequent functionalisation mostly rely on specialized directing groups on the arene that steer the selectivity towards the desired isomer by coordinating to the metal center. This leaves a functional group at the point of attachment within the molecule even after a potential removal of the initial functional handle. Complementary non-directed methods on the other hand suffer from regioselectivity issues, especially when the desired selectivity contrasts an intrinsic electronic or steric bias on the substrate. For iridium mediated borylations several highly selective charge mediated approaches have been described 1 but analogous systems remained elusive in Pd-catalysis. We describe, simultaneously with Maiti and coworkers , 2 the first meta-selective charge-controlled C–H olefination of arenes. 3 Our approach employs benzyl ammonium ions as substrates that interact non-covalently with the ligand via charge-charge and charge-dipole interactions. The precise nature of the ligand-substrate interaction and a dual role of the ligand were elucidated by means of in- depth mechanistic and computational analysis. A broad substrate scope can be accessed with representative examples giving meta -selectivities for unbiased substrates and even overcoming competing intrinsic reactivity trends. It was showcased that complementary substitution patterns compared to literature known ortho - and para - selective methods could be accessed employing otherwise analogous synthetic routes. The scalability and facile post-functionalisation render the ammonium functionality valuable as a linchpin for generating polysubstituted arenes. Hydrogenative defunctionalization, C–Het bond formation via substitution, and C–C bond formation via cross-coupling were demonstrated as subsequent transformations giving access to attractive compounds with otherwise challenging substitution patterns. TOC
References 1. J. E. Gillespie + , A. Fanourakis + and R. J. Phipps*, J. Am. Chem. Soc. , 2022, 144 , 18195. 2. N. Goswami+, S. K. Sinha+, P. Mondal, S. Adhya, A. Datta* and D. Maiti*, Chem , 2023, 9 , 989. 3. A. Mondal, M. Díaz-Ruiz + , F. Deufel + , F. Maseras* and M. van Gemmeren*, Chem , 2023, 9 , 1004. 4. + equal contribution, * corresponding author
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© The Author(s), 2023
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