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Flavin‐Catalyzed Aerobic Oxidative C−C Bond Formation by Metal/Light‐Free Cross‐Dehydrogenative Coupling

Hazuki Miyake, Hiroki Iida

2023Advanced Synthesis & Catalysis10 citationsDOIOpen Access PDF

Abstract

Abstract Biomimetic flavin catalysts enable green and selective aerobic oxidative transformations. However, most previous studies tended to focus on reproducing the enzymatic function of flavin monooxygenase, thereby limiting the applications of flavin catalysts to oxygen‐atom transfer reactions. We herein report a cross‐dehydrogenative coupling (CDC) between the sp 3 C−H bond of tetrahydroisoquinolines and the sp 3 and sp 2 C−H bonds of carbon nucleophiles, such as α‐methylene carbonyl compounds, nitromethane, and indoles, for C−C bond formation promoted by flavin catalysts. Flavin catalysis enables the oxidative C−H activation of tetrahydroisoquinolines and the efficient activation of molecular oxygen (1 atm) under mild and metal/light‐free conditions, thus facilitating a green aerobic CDC that generates benign water as the sole by‐product.

Topics & Concepts

ChemistryFlavin groupCatalysisPhotochemistryNucleophileOxidative coupling of methaneOxygenOrganic chemistryEnzymeCatalytic C–H Functionalization MethodsRadical Photochemical ReactionsSulfur-Based Synthesis Techniques
Flavin‐Catalyzed Aerobic Oxidative C−C Bond Formation by Metal/Light‐Free Cross‐Dehydrogenative Coupling | Litcius