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‘One Pot’ in situ Borylation by C-H Activation

Mechanism + Description

The Boron coupling partner is formed in situ via a C-H activation reaction catalyzed by an iridium catalyst. The reaction then occurs with the aryl/heteroaryl halide/Pd catalyst via the usual Suzuki mechanism.

General Comments

The recent development Miller and Hartwig (are these the scientists who made the ‘development’?) of Ir-based catalytic systems that enables the insertion of pinacolylborane directly into an unactivated Ar-H bond has opened up the exciting prospect of a much greener Suzuki reaction by obviating the need to prepare the arylboron intermediate from an aryl halide. The least sterically hindered Ar-H bond is activated (for example, the 5 position of a 1,3-disubstituted benzene ring regardless of the electronics of the substituents), which gives access to previously highly inaccessible substitution patterns. The telescoping of this reaction with the Suzuki coupling is still in its infancy, but it is an area of very active pursuit.

Key References

Preshlock, S. M.; Ghaffari, B.; Maligres, P. E.; Krska, S. W.; Maleczka, R. E., Jr.; Smith, M. R., III. High Throughput Optimization of Ir-Catalyzed C–H Borylation: A Tutorial for Practical Applications. J. Am. Chem. Soc. 2013, 135 (20), 7572–7582.

Tse, M. K.; Cho, J.; Smith, M. R., III. Regioselective Aromatic Borylation in an Inert Solvent. Org. Lett. 2001, 3 (18),  2831–2833.

Cho, J.; Tse, M. K.; Holmes, D.; Maleczka, R. E., Jr. Smith, M. R., III. Remarkably Selective Iridium Catalysts for the Elaboration of Aromatic C-H Bonds. Science. 2002, 295 (5553). 305-308.

Cho, J.; Iverson, C. N.; Smith, M. R., III. Steric and Chelate Directing Effects in Aromatic Borylation. J. Am. Chem. Soc. 2000, 122 (51), 12868–12869.

Relevant Scale-Up Examples with Scheme

None located.