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  • Ligand-controlled divergent dehydrogenative reactions of carboxylic acids via C-H activation.

Ligand-controlled divergent dehydrogenative reactions of carboxylic acids via C-H activation.

Science (New York, N.Y.) (2021-11-12)
Zhen Wang, Liang Hu, Nikita Chekshin, Zhe Zhuang, Shaoqun Qian, Jennifer X Qiao, Jin-Quan Yu
ABSTRACT

Dehydrogenative transformations of alkyl chains to alkenes through methylene carbon-hydrogen (C–H) activation remain a substantial challenge. We report two classes of pyridine-pyridone ligands that enable divergent dehydrogenation reactions through palladium-catalyzed β-methylene C–H activation of carboxylic acids, leading to the direct syntheses of α,β-unsaturated carboxylic acids or γ-alkylidene butenolides. The directed nature of this pair of reactions allows chemoselective dehydrogenation of carboxylic acids in the presence of other enolizable functionalities such as ketones, providing chemoselectivity that is not possible by means of existing carbonyl desaturation protocols. Product inhibition is overcome through ligand-promoted preferential activation of C(sp3)–H bonds rather than C(sp2)–H bonds or a sequence of dehydrogenation and vinyl C–H alkynylation. The dehydrogenation reaction is compatible with molecular oxygen as the terminal oxidant.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
6-(2-(Quinolin-2-yl)propan-2-yl)pyridin-2-ol, ≥95%
Sigma-Aldrich
6-(Quinolin-2-yl)pyridin-2(1H)-one, ≥95%
Sigma-Aldrich
6-(2-(5-chloropyridin-2-yl)-1-phenylpropan-2-yl)pyridin-2-ol
Sigma-Aldrich
6-(1-Cyclohexyl-1-(5-methylpyridin-2-yl)ethyl)pyridin-2(1H)-one, ≥95%