The iridium-catalyzed C-H borylation of benzamides typically leads to meta and para selectivities using state-of-the-art iridium-based N,N-chelating bipyridine ligands. However, reaching ortho selectivity patterns requires extensive trial-and-error screening via molecular design at the ligand first coordination sphere. Herein, we demonstrate that triazolylpyridines are excellent ligands for the selective iridium-catalyzed ortho C-H borylation of tertiary benzamides and, importantly, we demonstrate the almost negligible effect of the first coordination sphere in the selectivity, which is so far unprecedented in iridium C-H bond borylations. Remarkably, the activity is dramatically enhanced by exploiting a remote Zn⋯O C weak interaction between the substrate and a rationally designed molecular-recognition site in the catalyst. Kinetic studies and DFT calculations indicate that the iridium-catalyzed C-H activation step is not rate-determining, this being unique for remotely controlled C-H functionalizations. Consequently, a previously established supramolecular iridium catalyst designed for meta-borylation of pyridines is now compatible with the ortho-borylation of benzamides, a regioselectivity switch that is counter-intuitive regarding precedents in the literature. In addition, we highlight the role of the cyclohexene additive in avoiding the formation of undesired side-products as well as accelerating the HBpin release event that precedes the catalyst regeneration step, which is highly relevant for the design of powerful and selective iridium borylating catalysts.

Repurposing a supramolecular iridium catalyst via secondary Zn⋯O 00000000 00000000 00000000 00000000 11111111 00000000 11111111 00000000 00000000 00000000 C weak interactions between the ligand and substrate leads to ortho-selective C(sp2)-H borylation of benzamides with unusual kinetics

Tomasini M.;
2024-01-01

Abstract

The iridium-catalyzed C-H borylation of benzamides typically leads to meta and para selectivities using state-of-the-art iridium-based N,N-chelating bipyridine ligands. However, reaching ortho selectivity patterns requires extensive trial-and-error screening via molecular design at the ligand first coordination sphere. Herein, we demonstrate that triazolylpyridines are excellent ligands for the selective iridium-catalyzed ortho C-H borylation of tertiary benzamides and, importantly, we demonstrate the almost negligible effect of the first coordination sphere in the selectivity, which is so far unprecedented in iridium C-H bond borylations. Remarkably, the activity is dramatically enhanced by exploiting a remote Zn⋯O C weak interaction between the substrate and a rationally designed molecular-recognition site in the catalyst. Kinetic studies and DFT calculations indicate that the iridium-catalyzed C-H activation step is not rate-determining, this being unique for remotely controlled C-H functionalizations. Consequently, a previously established supramolecular iridium catalyst designed for meta-borylation of pyridines is now compatible with the ortho-borylation of benzamides, a regioselectivity switch that is counter-intuitive regarding precedents in the literature. In addition, we highlight the role of the cyclohexene additive in avoiding the formation of undesired side-products as well as accelerating the HBpin release event that precedes the catalyst regeneration step, which is highly relevant for the design of powerful and selective iridium borylating catalysts.
2024
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11386/4888355
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