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A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species
Published on: August 16, 2018
Thianthrenium Salt-Mediated Site-Selective Coupling of Arenes with Enynones
Shihaozhi Wang1, Jia-Hui Shi1, Shan Xu1
1State Key Laboratory of Anti-Infective Drug Discovery and Development, Guangdong Provincial Key Laboratory of Chiral Molecules and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou510006, China.
Abstract:
Herein, we report a palladium-catalyzed, diazo-free, regioselective carbene coupling reaction of unactivated arenes with furyl carbenes, which are readily generated in situ from enynones, serving as safe and practical surrogates for traditional carbene sources. In this transformation, arenes are first thianthrenated, followed by a cascade reaction of cycloisomerization, migratory insertion, and β-hydride elimination with enynones to afford furyl-substituted alkenylarenes. This highly site-selective olefination features excellent safety, a broad substrate scope, and good tolerance of halogen substituents. Notably, the successful derivatization of drug(like) molecules demonstrates the substantial potential of this method for the late-stage functionalization of arene-based drugs.
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