Palladium-catalyzed decarboxylative, decarbonylative and dehydrogenative C(sp2)–H acylation at room temperature?

Organic & Biomolecular Chemistry Pub Date: 2017-07-20 DOI: 10.1039/C7OB01466J

Abstract

Over the past few decades, an impressive array of C–H activation methodology has been developed for organic synthesis. However, due to the inherent inertness of the C–H bonds (e.g. ～110 kcal mol?1 for the cleavage of C(aryl)–H bonds) harsh reaction conditions have been realized to overcome high energetic transition states resulting in a limited substrate scope and functional group tolerance. Therefore, the development of mild C–H functionalization protocols is in high demand to exploit the full potential of the C–H activation strategy in the synthesis of a complex molecular framework. Although, electron-rich substrates undergo electrophilic metalation under relatively mild conditions, electron-deficient substrates proceed through a rate-limiting C–H insertion under forcing conditions at high temperature. In addition, a stoichiometric amount of toxic silver salt is frequently used in palladium catalysis to facilitate the C–H activation process which is not acceptable from the environmental and industrial standpoint. We report herein, a Pd(II)-catalyzed decarboxylative C–H acylation of 2-arylpyridines with α-ketocarboxylic acids under mild conditions. The present protocol does not require stoichiometric silver(I) salts as additives and proceeds smoothly at ambient temperature. A novel decarbonylative C–H acylation reaction has also been accomplished using aryl glyoxals as acyl surrogates. Finally, a practical C–H acylation via a dehydrogenative pathway has been demonstrated using commercially available benzaldehydes and aqueous hydroperoxides. We also disclose that acetonitrile solvent is optimal for the acylation reaction at room temperature and has a prominent role in the reaction outcome. Control experiments suggest that the acylation reaction via decarboxylative, decarbonylative and dehydrogenative proceeds through a radical pathway. Thus we disclose a practical protocol for the sp2 C–H acylation reaction.

Graphical abstract: Palladium-catalyzed decarboxylative, decarbonylative and dehydrogenative C(sp2)–H acylation at room temperature
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