Recent developments in photoredox-catalyzed remote ortho and para C-H bond functionalizations

Abstract

In recent years, the research area of direct C-H bond functionalizations was growing exponentially not only due to the ubiquity of inert C-H bonds in diverse organic compounds, including bioactive natural and nonnatural products, but also due to its impact on the discovery of pharmaceutical candidates and the total synthesis of intricate natural products. On the other hand, more recently, the field of photoredox catalysis has become an indispensable and unparalleled research topic in modern synthetic organic chemistry for the constructions of challenging bonds, having the foremost scope in academia, pharmacy, and industry. Therefore, the development of green, simpler, and effective methodologies to accomplish direct C-H bond functionalization is well overdue and highly desirable to the scientific community. In this review, we mainly highlight the impact on, and the utility of, photoredox catalysts in inert ortho and para C-H bond functionalizations. Although a surge of research papers, including reviews, demonstrating C-H functionalizations have been published in this vital area of research, to our best knowledge, this is the first review that focuses on ortho and para C-H functionalizations by photoredox catalysis to provide atom- and step-economic organic transformations. We are certain that this review will act as a promoter to highlight the application of photoredox catalysts for the functionalization of inert bonds in the domain of synthetic organic chemistry.

Keywords: dual catalysis; light; ortho and para C–H bond functionalization; photoredox catalysis.

Figure 1

List of photoredox catalysts used for C–H bond functionalizations.

Figure 2

List of metal-based photoredox catalysts used in this review article.

Figure 3

Jablonski diagram.

Figure 4

Photoredox catalysis via reductive or oxidative pathways. D = donor, A = acceptor, S = substrate, PC = photoredox catalyst, RDP = reductive quenching pathway, OQP = oxidative quenching pathway.

Figure 5

Schematic representation of the combination of photoredox catalysis and transition metal catalysis.

Scheme 1

Weinreb amide C–H olefination.

Figure 6

Mechanism for the formation of 21 from 19 using photoredox catalyst 11.

Scheme 2

C–H olefination of phenolic ethers.

Scheme 3

Decarboxylative acylation of acetanilides.

Figure 7

Mechanism for the formation of 30 from acetanilide derivatives.

Scheme 4

Synthesis of fluorenone derivatives by intramolecular deoxygenative acylation of biaryl carboxylic acids.

Figure 8

Mechanism for the photoredox-catalyzed synthesis of fluorenone derivatives.

Scheme 5

Synthesis of benzothiazoles via aerobic C–H thiolation.

Figure 9

Plausible mechanism for the construction of benzothiazoles from benzothioamides.

Scheme 6

Synthesis of benzothiazoles via oxidant-free C–H thiolation.

Figure 10

Mechanism involved in the synthesis of benzothiazoles via oxidant-free C–H thiolation.

Scheme 7

Synthesis of indoles via C–H cyclization of anilides with alkynes.

Scheme 8

Preparation of 3-trifluoromethylcoumarins via C–H cyclization of arylpropiolate esters.

Figure 11

Mechanistic pathway for the synthesis of coumarin derivatives via C–H cyclization.

Scheme 9

Monobenzoyloxylation without chelation assistance.

Figure 12

Plausible mechanism for the formation of 71 from 70.

Scheme 10

Aryl-substituted arenes prepared by inorganic photoredox catalysis using 12a.

Figure 13

Proposed mechanism for C–H arylations in the presence of 12a and a Pd catalyst.

Scheme 11

Arylation of purines via dual photoredox catalysis.

Scheme 12

Arylation of substituted arenes with an organic photoredox catalyst.

Scheme 13

C–H trifluoromethylation.

Figure 14

Proposed mechanism for the trifluoromethylation of 88.

Scheme 14

Synthesis of benzo-3,4-coumarin derivatives.

Figure 15

Plausible mechanism for the synthesis of substituted coumarins.

Scheme 15

Oxidant-free oxidative phosphonylation.

Figure 16

Mechanism proposed for the phosphonylation reaction of 100.

Scheme 16

Nitration of anilines.

Figure 17

Plausible mechanism for the nitration of aniline derivatives via photoredox catalysis.

Scheme 17

Synthesis of carbazoles via intramolecular amination.

Figure 18

Proposed mechanism for the formation of carbazoles from biaryl derivatives.

Scheme 18

Synthesis of substituted phenols using QuCN.

Figure 19

Mechanism for the synthesis of phenol derivatives with photoredox catalyst 8.

Scheme 19

Synthesis of substituted phenols with DDQ (5).

Figure 20

Possible mechanism for the generation of phenols with the aid of photoredox catalyst 5.

Scheme 20

Aerobic bromination of arenes using an acridinium-based photocatalyst.

Scheme 21

Aerobic bromination of arenes with anthraquinone.

Figure 21

Proposed mechanism for the synthesis of monobrominated compounds.

Scheme 22

Chlorination of benzene derivatives with Mes-Acr-MeClO₄ (2).

Figure 22

Mechanism for the synthesis of 131 from 132.

Scheme 23

Chlorination of arenes with 4CzIPN (5a).

Figure 23

Plausible mechanism for the oxidative photocatalytic monochlorination using 5a.

Scheme 24

Monofluorination using QuCN-ClO₄ (8).

Scheme 25

Fluorination with fluorine-18.

Scheme 26

Aerobic amination with acridinium catalyst 3a.

Figure 24

Plausible mechanism for the aerobic amination using acridinium catalyst 3a.

Scheme 27

Aerobic aminations with semiconductor photoredox catalyst 18.

Scheme 28

Perfluoroalkylation of arenes.

Scheme 29

Synthesis of benzonitriles in the presence of 3a.

Figure 25

Plausible mechanism for the synthesis of substituted benzonitrile derivatives in the presence of 3a.