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Ir-Catalyzed Ligand-Free Directed C-H Borylation of Arenes and Pharmaceuticals: Detailed Mechanistic Understanding
Journal
Journal of Organic Chemistry
ISSN
00223263
Date Issued
2022-03-18
Author(s)
Mahamudul Hassan, Mirja Md
Mondal, Biplab
Singh, Sukriti
Haldar, Chabush
Chaturvedi, Jagriti
Bisht, Ranjana
Sunoj, Raghavan B.
Chattopadhyay, Buddhadeb
Abstract
An efficient method for Ir-catalyzed ligand free ortho borylation of arenes (such as, 2-phenoxypyridines, 2-anilinopyridines, benzylamines, benzylpiperazines, benzylmorpholines, benzylpyrrolidine, benzylpiperidines, benzylazepanes, α-amino acid derivatives, aminophenylethane derivatives, and other important scaffolds) and pharmaceuticals has been developed. The reaction underwent via an interesting mechanistic pathway, as revealed by the detailed mechanistic investigations by using kinetic isotope studies and DFT calculations. The catalytic cycle is found to involve the intermediacy of an Ir-boryl complex where the substrate C-H activation is the turnover determining step, intriguingly without any appreciable primary KIE. The method displays a broad range of substrate scope and functional group tolerance. Numerous late-stage borylation of various important molecules and drugs were achieved using this developed strategy. The borylated compounds were further converted into more valuable functionalities. Moreover, utilizing the benefit of the B-N intramolecular interaction of the mono borylated compounds, an operationally simple method has been developed for the selective diborylation of 2-phenoxypyridines and numerous functionalized arenes. Furthermore, the synthetic utility has been showcased with the removal of the pyridyl directing group from the borylated product to achieve ortho borylated phenol along with the ipso-borylation for the preparation of 1,2-diborylated benzene.