Comprehensive Overview of Progress in Functionalization of 2‐Pyridone and 2, 4 ‐Dihydroxy Pyridine: Key Constituents of Vital Natural Products

Abstract

Nitrogen heterocycles have found a key role in biologically active natural products. Pyridones, specifically 2‐pyridone and 2,4‐dihydoxypyridine are an extensive class of compounds with reported occurrence in many natural products. Therefore, the methods for generation of functionalized pyridones are of great interest since their discovery. From traditional coupling to transition metal catalyzed C−H functionalization and transition metal free C−H functionalization, this field has witnessed enormous growth. In the present review, we aim to present a comprehensive overview of pyridone functionalization for young researchers and invite the scientific community to come up with more environment friendly, economic and transition metal free methodologies for corresponding functionalizations.

Umpolung Synthesis of Pyridyl Ethers by BiV‐Mediated O‐Arylation of Pyridones

“…This compares favorably to the previously reported method for O-arylation of pyridones with boronic acids, which is not only limited to 6substituted pyridones, but which also does not tolerate orthosubstitution on the boronic acid component. [13] The ability to transfer electron-poor aryl moieties (18, 19, 26, 27, 39), including from pyridylboronic acids (19,27), further illustrates the complementarity between our pyridone arylation approach and SNAr.…”

“…[a] Reactions performed on a 0.02 mmol scale. Yields determined by19 F NMR spectroscopy vs internal standard (4,4′-bis(trifluoromethyl)biphenyl). [b] Reaction performed in a sealed tube; reaction temperature refers to that of the heating block.…”

Umpolung Synthesis of Pyridyl Ethers by BiV‐Mediated O‐Arylation of Pyridones

“…This compares favorably to the previously reported method for O-arylation of pyridones with boronic acids, which is not only limited to 6-substituted pyridones, but which also does not tolerate ortho-substitution on the boronic acid component. [13] The ability to transfer electronpoor aryl moieties (18, 19, 26, 27, 39), including from pyridylboronic acids (19,27), further illustrates the complementarity between our pyridone arylation approach and S N Ar.…”

“…Robustness screen of the oxidation and arylation steps. Yields determined by 19 F NMR spectroscopic analysis vs internal standard.…”

Rh(III)-Catalyzed Weakly Coordinating 2-Pyridone-Directed Oxidative Annulation Using Internal Alkynes: A Reversal in Selectivity

“…Among various known 2-pyridone-based moieties, the N -aryl 2-pyridone scaffold is considered as an important structural scaffold due to its frequent presence in pharmaceuticals, drug molecules, and organic materials (Figure ). Therefore, newer step-economic direct modifications of this scaffold are in great demand . Recently, internal alkyne was extensively explored as a coupling partner for the site-selective C–H bond functionalizations of 2-pyridone scaffolds under various transition metal-catalyzed conditions .…”