Flavin-Catalyzed Aerobic α-Functionalization of 1,2,3,4-Tetrahydro-isoquinolines: Application to C=O and C-O Bond
Hazuki Miyake1, Taiki Fukuzako1, Hiroki Iida1
1Department of Chemistry, Graduate School of Natural Science and Technology, Shimane University, 1060 Nishikawatsu, Matsue, Shimane 690-8504, Japan.
Abstract:
Under metal- and light-free conditions, cationic flavin catalysts enable the aerobic α-functionalization of 1,2,3,4-tetrahydroisoquinolines: (i) α-oxygenation to 3,4-dihydroisoquinolones (C=O formation) and (ii) α-alkoxylation (C-O formation) via cross-dehydrogenative coupling with alcohols. The aerobic α-C=O and C-O bond formations occur via two complementary α-C-H activation pathways catalyzed by flavins with tunable redox properties. These reactions proceed in molecular oxygen or air atmospheres (1 atm) without any additional sacrificial reagents (e.g., external reductants) and without light, unlike conventional flavin-catalyzed aerobic oxidation reactions.
Related Concept Videos
Oxidation of Phenols to Quinones
o-hydroxy phenols are oxidized to o-quinones and p-hydroxy phenols to p-quinones. Such redox reactions involve the transfer of two electrons and two protons. The reversible redox...
Electrophilic Aromatic Substitution: Fluorination and Iodination of Benzene
Preparation of 1° Amines: Hofmann and Curtius Rearrangement Mechanism
Vicinal Diols via Reductive Coupling of Aldehydes or Ketones: Pinacol Coupling Overview
Preparation of 1° Amines: Hofmann and Curtius Rearrangement Overview
Acid-Catalyzed α-Halogenation of Aldehydes and Ketones
In the first step of the mechanism, the acid protonates the carbonyl oxygen resulting in a resonance-stabilized cation, which subsequently loses an α-hydrogen to form an enol tautomer. The C=C bond in an enol is highly nucleophilic because of the electron-donating nature of the –OH group. Consequently, the double bond attacks an electrophilic halogen to form a...


