Ruthenium-Catalyzed meta-Selective C-H Mono- and Difluoromethylation of Arenes through ortho-Metalation Strategy

Zhong-Yuan Li; Liang Li; Qi-Li Li; Kun Jing; Hui Xu; Guan-Wu Wang

doi:10.1002/chem.201700354

Ruthenium-Catalyzed meta-Selective C-H Mono- and Difluoromethylation of Arenes through ortho-Metalation Strategy

Chemistry. 2017 Mar 8;23(14):3285-3290. doi: 10.1002/chem.201700354. Epub 2017 Feb 16.

Authors

Zhong-Yuan Li¹, Liang Li¹, Qi-Li Li¹, Kun Jing¹, Hui Xu¹, Guan-Wu Wang¹

Affiliation

¹ Hefei National Laboratory for Physical Sciences at Microscale, CAS Key Laboratory of Soft Matter Chemistry, Collaborative Innovation Center of Chemistry for Energy Materials (iChEM), and Department of Chemistry, University of Science and Technology of China, Hefei, Anhui, 230026, P. R. China.

PMID: 28120380
DOI: 10.1002/chem.201700354

Abstract

The first example for the ruthenium-catalyzed ligand-directed meta-selective C-H mono- and difluoromethylation is developed, affording a variety of new meta-mono- and difluoromethylated 2-phenylpyridines, 2-phenylpyrimidines, and 1-phenylpyrazoles in moderate-to-good yields. This new transformation exhibits broad substrate scope, good functional group tolerance, and high efficiency, and offers a practical approach to synthesize mono- and difluoromethylated arenes. Mechanistic studies indicate that a reaction pathway involving palladium-initiated radical species is involved in the catalytic cycle. The new dual catalytic system consisting of compatible ruthenium(II) and palladium(0) complexes enables the key processes of C-H activation and mono-/difluoromethyl-radical formation to occur and achieves the meta-selective functionalization efficiently. In addition, the present protocol can also be extended to non-fluoromethylation.

Keywords: fluoromethyl radical; fluoromethylation; meta-C−H activation; palladium catalysis; ruthenium catalysis.