期刊
ACS CATALYSIS
卷 8, 期 9, 页码 8324-8335出版社
AMER CHEMICAL SOC
DOI: 10.1021/acscatal.8b02816
关键词
C-H activation; ruthenium catalysis; oxidative C-H/C-H cross-coupling; dual chelation-assisted strategy; 2,2 '-difunctional biaryl
资金
- National NSF of China [21432005, 21772020]
- Comprehensive Training Platform of Specialized Laboratory, College of Chemistry, Sichuan University
We herein illustrate the dual chelation-assisted strategy for a Ru(II)-catalyzed oxidative ortho-C-H/C-H cross-coupling of phenols with (hetero)aromatic amides with the aid of Zn(OTf)(2), which enables to rapidly assemble a rich library of 2'-hydroxybiphenyl-2-carboxylic acid derivatives. This protocol features broad substrate scope, excellent functional group tolerance, air as the terminal oxidant, low molar ratio of coupling partners, and scale-up synthesis. Particularly, this methodology is tolerant of more complex natural product derivatives, thus providing an opportunity for late-stage functionalization. This protocol is also used as a key step for the concise synthesis of Palomid 529, a drug in development for the treatment of glioblastoma and neovascular age-related macular degeneration. With a combination of experimental and theoretical methods, we get more insight into the essential issues of strategy determining the reaction process. The stronger coordinating ability of 2-aryloxypyridine and the less steric hindrance of amide are pivotal to the high chemoselectivity of cross-coupling over homocoupling. The first C-H bond activation step takes place at the amide substrate, and the following C-H bond activation at 2-aryloxypyridine is involved in the rate-determined step.
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