Benzylic C-H Oxidation: Recent Advances and Applications in Heterocyclic Synthesis

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2025 Jan 8

PMID 39770135

Authors

Nonhlelo Majola

Vineet Jeena

Affiliations

Soon will be listed here.

Abstract

Benzylic C-H oxidation to form carbonyl compounds, such as ketones, is a fundamental transformation in organic synthesis as it allows for the preparation of versatile intermediates. In this review, we highlight the synthesis of aromatic ketones via catalytic, electrochemical, and photochemical oxidation of alkylarenes using different catalysts and oxidants in the past 5 years. Additionally, we also discuss the synthesis of heterocyclic molecules using benzylic C-H oxidation as a key step. These methods can potentially be used in medicinal, synthetic, and inorganic chemistry.

References

Mhlongo J, Brasil E, de la Torre B, Albericio F . Naturally Occurring Oxazole-Containing Peptides. Mar Drugs. 2020; 18(4). PMC: 7231064. DOI: 10.3390/md18040203. View

Xue M, Pan T, Shao Z, Wang W, Li H, Zhao L . Sustainable Electrochemical Benzylic C-H Oxidation Using MeOH as an Oxygen Source. ChemSusChem. 2024; 17(10):e202400028. DOI: 10.1002/cssc.202400028. View

Tan H, Zhou X, Gong T, You H, Zheng Q, Zhao S . Anderson-type polyoxometalate-based metal-organic framework as an efficient heterogeneous catalyst for selective oxidation of benzylic C-H bonds. RSC Adv. 2024; 14(1):364-372. PMC: 10759227. DOI: 10.1039/d3ra07120k. View

Landowski T, Samulitis B, Dorr R . The diaryl oxazole PC-046 is a tubulin-binding agent with experimental anti-tumor efficacy in hematologic cancers. Invest New Drugs. 2013; 31(6):1616-25. PMC: 3899824. DOI: 10.1007/s10637-013-0019-8. View

Mazibuko M, Jeena V . Synthesis of 2,4,5-Trisubstituted Oxazoles from Copper-Mediated Benzylic sp C-H Aerobic Oxidative Annulation of Ketones and Amines via a Cascade Reaction. J Org Chem. 2022; 88(2):1227-1234. DOI: 10.1021/acs.joc.2c02148. View

Jayram J, Jeena V . An iodine/DMSO-catalyzed sequential one-pot approach to 2,4,5-trisubstituted-1-imidazoles from α-methylene ketones. RSC Adv. 2022; 8(66):37557-37563. PMC: 9089320. DOI: 10.1039/c8ra07238h. View

Weng Q, Wang D, Guo P, Fang L, Hu Y, He Q . Q39, a novel synthetic Quinoxaline 1,4-Di-N-oxide compound with anti-cancer activity in hypoxia. Eur J Pharmacol. 2008; 581(3):262-9. DOI: 10.1016/j.ejphar.2007.12.006. View

Lu X, Liu X, Wan B, Franzblau S, Chen L, Zhou C . Synthesis and evaluation of anti-tubercular and antibacterial activities of new 4-(2,6-dichlorobenzyloxy)phenyl thiazole, oxazole and imidazole derivatives. Part 2. Eur J Med Chem. 2012; 49:164-71. DOI: 10.1016/j.ejmech.2012.01.007. View

Luo L, Zhang T, Wang M, Yun R, Xiang X . Recent Advances in Heterogeneous Photo-Driven Oxidation of Organic Molecules by Reactive Oxygen Species. ChemSusChem. 2020; 13(19):5173-5184. DOI: 10.1002/cssc.202001398. View

10.

Yamaguchi J, Yamaguchi A, Itami K . C-H bond functionalization: emerging synthetic tools for natural products and pharmaceuticals. Angew Chem Int Ed Engl. 2012; 51(36):8960-9009. DOI: 10.1002/anie.201201666. View

11.

Nguyen K, Nguyen V, Tran H, Pham P . Organo-photocatalytic C-H bond oxidation: an operationally simple and scalable method to prepare ketones with ambient air. RSC Adv. 2023; 13(11):7168-7178. PMC: 9986805. DOI: 10.1039/d3ra00332a. View

12.

Zhang H, Liu M, Zhang Z, Zhang Q, Li H, Sun Y . From Lignin to Value-Added Pharmaceutical Intermediates Based on a Benzylic Oxidation Method with O. Org Lett. 2024; 26(29):6076-6080. DOI: 10.1021/acs.orglett.4c01608. View

13.

Sahin Y, Sika-Nartey A, Ercan K, Kocak Y, Senol S, Ozensoy E . Precious Metal-Free LaMnO Perovskite Catalyst with an Optimized Nanostructure for Aerobic C-H Bond Activation Reactions: Alkylarene Oxidation and Naphthol Dimerization. ACS Appl Mater Interfaces. 2021; 13(4):5099-5110. DOI: 10.1021/acsami.0c20490. View

14.

Bo C, Li M, Chen F, Liu J, Dai B, Liu N . Visible-Light-Initiated Air-Oxygenation of Alkylarenes to Carbonyls Mediated by Carbon Tetrabromide in Water. ChemSusChem. 2023; 17(1):e202301015. DOI: 10.1002/cssc.202301015. View

15.

Shibata S, Sugahara K, Kamata K, Hara M . Liquid-phase oxidation of alkanes with molecular oxygen catalyzed by high valent iron-based perovskite. Chem Commun (Camb). 2018; 54(50):6772-6775. DOI: 10.1039/c8cc02185f. View

16.

Kong L, Meng J, Tian W, Liu J, Hu X, Jiang Z . I-Catalyzed Carbonylation of α-Methylene Ketones to Synthesize 1,2-Diaryl Diketones and Antiviral Quinoxalines in One Pot. ACS Omega. 2022; 7(1):1380-1394. PMC: 8757360. DOI: 10.1021/acsomega.1c06017. View

17.

Yar M, Bajda M, Shahzad S, Ullah N, Gilani M, Ashraf M . Organocatalyzed solvent free an efficient novel synthesis of 2,4,5-trisubstituted imidazoles for α-glucosidase inhibition to treat diabetes. Bioorg Chem. 2014; 58:65-71. DOI: 10.1016/j.bioorg.2014.11.006. View

18.

Deng L, Huang B, Liu Y . Copper(ii)-mediated, carbon degradation-based amidation of phenylacetic acids toward N-substituted benzamides. Org Biomol Chem. 2018; 16(9):1552-1556. DOI: 10.1039/c8ob00064f. View

19.

Li P, Wang Y, Wang X, Wang Y, Liu Y, Huang K . Selective Oxidation of Benzylic C-H Bonds Catalyzed by Cu(II)/{PMo}. J Org Chem. 2020; 85(5):3101-3109. DOI: 10.1021/acs.joc.9b02997. View

20.

Niu K, Shi X, Ding L, Liu Y, Song H, Wang Q . HCl-Catalyzed Aerobic Oxidation of Alkylarenes to Carbonyls. ChemSusChem. 2021; 15(2):e202102326. DOI: 10.1002/cssc.202102326. View