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

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.

Keywords: alkylarenes; benzylic C–H oxidation; heterocycles; imidazoles; ketones; oxazoles; quinoxalines; review.

Figure 1

Biologically active compounds comprising aromatic ketone scaffold.

Scheme 1

Oxidation of alkylarene [13,14].

Scheme 2

Synthesis of aromatic ketones reported by Ajjou and Rahman.

Scheme 3

Selected scope for aromatic ketones reported by Liu and co-workers.

Scheme 4

Alkylarene oxidation reported by Zhao and co-workers.

Scheme 5

Alkylarene oxidation reported by Hao and co-workers.

Scheme 6

Oxidation of alkylarenes reported by Shen and co-workers.

Figure 2

Structure of 5,10,15,20-Tetrakis(2,3,6-trichlorophenyl)porphyrin Cobalt(II).

Scheme 7

Alkylarene oxidation to aromatic ketones reported by Duan and co-workers.

Scheme 8

Alkylarene oxidation to aromatic ketones reported by Ozensoy and co-workers.

Scheme 9

Alkylarene oxidation to aromatic ketones reported by Maurya and co-workers.

Scheme 10

Alkylarene oxidation to aromatic ketones reported by Zhou and co-workers.

Scheme 11

Alkylarene oxidation to aromatic ketones reported by Tuna and co-workers.

Scheme 12

Alkylarene oxidation to aromatic ketones reported by Tantirungrotechai and co-workers.

Scheme 13

Alkylarene oxidation reported by Yin and co-workers.

Scheme 14

Alkylarene oxidation reported by Hara and co-workers.

Scheme 15

Alkylarene oxidation reported by Chen, Li and co-workers.

Scheme 16

Diphenylmethane oxidation to benzophenone reported by Soni and co-workers.

Scheme 17

Alkylarene oxidation reported by Peng and co-workers.

Scheme 18

Alkylarene oxidation reported by Yu and co-workers.

Scheme 19

Alkylarene oxidation reported by Song and co-workers.

Scheme 20

Alkylarene oxidation reported by Zhao, Xuan and co-workers.

Scheme 21

Alkylarene oxidation reported by He and co-workers.

Scheme 22

Alkylarene oxidation to aromatic ketones reported by Zhu and co-workers.

Scheme 23

Alkylarene oxidation to aromatic ketones reported by Najminejad.

Scheme 24

(Hetero)benzylic C–H oxidation reported by Li and co-workers.

Scheme 25

Het(aryl) oxidation reported by Gan and co-workers.

Scheme 26

Benzylic C–H oxidation as key intermediate in pharmaceutical compound synthesis from lignin.

Scheme 27

Trifluoromethanesulfinate-mediated synthesis of aryl ketones from alkylarenes by Fu and co-workers. * indicates light activation.

Scheme 28

Alkylarene oxidation reported by Duan and co-workers. * indicates activation by light.

Scheme 29

Alkylarene oxidation reported by Sirkosi and co-workers.

Scheme 30

Alkylarene oxidation to aromatic ketones reported by Niu, Wang and co-workers.

Scheme 31

Alkylarene oxidation reported by Chen, Li, Xu and co-workers.

Scheme 32

Scale-up synthesis of xanthone reported by Nguyen and co-workers.

Scheme 33

Alkylarene oxidation reported by Xu, Li and co-workers.

Scheme 34

Alkylarene oxidation to ketones reported by Chen and co-workers.

Scheme 35

Alkylarene oxidation reported by Guo and co-workers. * indicates activation by light.

Scheme 36

Alkylarene oxidation reported by Kazemi and co-workers.

Scheme 37

Alkylarene oxidation to aromatic ketones reported by Zha, Wang and co-workers.

Scheme 38

Application of an alkylarene electro-oxidative system to dyclonine intermediate (ketone) reported by Liu and co-workers.

Scheme 39

Alkylarene oxidation reported by Bai and co-workers.

Scheme 40

Alkylarene oxidation reported by Zhang and co-workers.

Scheme 41

Alkylarene oxidation reported by Zhao, Zhou, Zhang and co-workers.

Scheme 42

Alkylarene oxidation reported by Jia and co-workers.

Scheme 43

Alkylarene oxidation reported by Shen, Ye and co-workers.

Figure 3

Biologically important quinoxalines.

Scheme 44

Quinoxaline synthesis reported by Yin and co-workers.

Scheme 45

Synthesis of quinoxalines reported by Li, Bai and co-workers.

Scheme 46

Synthesis of quinoxalines via benzylic C–H oxidation reported by Liu and co-workers.

Figure 4

Examples of biologically important 2,4,5-trisubstituted imidazoles.

Scheme 47

Imidazole synthesis reported by Jayram and Jeena.

Scheme 48

Synthesis of 2,4,5-trisubstituted imidazoles reported by Jayram and Jeena.

Figure 5

Examples of biologically important oxazoles.

Scheme 49

Synthesis of oxazole reported by Mazibuko and Jeena.