A Bioinspired Catalytic Aerobic Functionalization of Phenols: Regioselective Construction of Aromatic C–N and C–O Bonds

Abstract

We report a bioinspired approach for the regioselective construction of both aromatic C–O and C–N bonds through the dehydrogenative coupling of phenols and aliphatic amines. Mechanistically, the process hinges on the ortho-oxygenation of phenols to ortho-quinones followed by aromatic C–N bond formation through a condensation/redox isomerization cascade. Overall, the process enables the regioselective formation of aromatic C–O and C–N bonds directly from C–H bonds under mild reaction conditions.

Selectivity in the Aerobic Dearomatization of Phenols: Total Synthesis of Dehydronornuciferine by Chemo‐ and Regioselective Oxidation

“…Reduction with hydride or addition of ethanethiol provides differentially substituted 3,4‐dihyroxyphenanthrenes 12 or 13 , respectively (Scheme B) . Condensation of an aryl hydrazine or hydrazide occurs at the less sterically encumbered C3 carbonyl to provide push‐pull azophenols 14 or 15 ,. Related azo switches possess red‐shifted absorbance properties and fast thermal relaxation, which are attractive for fast information transmission in biologically relevant contexts .…”

Scrabbling around in Synthetic Nuances Managing Sodium Compounds: Bisphenol/Bisnaphthol Synthesis by Hydroxyl Group Masking

“…In this context, the search for new practical protecting groups for functionalized phenols remains a synthetic problem of high importance. 10 − 13 Ethers are classical and, quite possibly, one of the most widely used functional groups for phenols. Therefore, studies focused on the mechanistic aspects of the incorporation of the ether group into a phenolic reagent might reveal new details about the masking process, opening new synthetic possibilities.…”

Primary α-tertiary amine synthesis via α-C–H functionalization

“…The mechanism involves the condensation of a quinone co-factor with the primary amine substrate and a subsequent formal [1,5] H-shift from the α-position of the amine to generate a reactive imine, which is then hydrolyzed to afford the aldehyde product. Despite elegant early work on quinone-mediated amine oxidation by McCoy and Day,15 and Corey,16 the elucidation of the mechanism of this biotransformation has paved the way for increasing applications in contemporary synthesis17 with notable contributions from Stahl,18 Kobayashi,19 and Fleury20 in amine oxidation, from Qu,9a,21 and Clift7 a in amine functionalization, and from Lumb in heterocycle synthesis 22,23…”