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. 2022 Feb 16;144(6):2399-2414.
doi: 10.1021/jacs.1c10783. Epub 2022 Jan 27.

A Perspective on Late-Stage Aromatic C-H Bond Functionalization

Li Zhang  1 , Tobias Ritter  1
Affiliations

A Perspective on Late-Stage Aromatic C-H Bond Functionalization

Li Zhang et al. J Am Chem Soc. .

Abstract

Late-stage functionalization of C-H bonds (C-H LSF) can provide a straightforward approach to the efficient synthesis of functionalized complex molecules. However, C-H LSF is challenging because the C-H bond must be functionalized in the presence of various other functional groups. In this Perspective, we evaluate aromatic C-H LSF on the basis of four criteria─reactivity, chemoselectivity, site-selectivity, and substrate scope─and provide our own views on current challenges as well as promising strategies and areas of growth going forward.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Electrophilic Aromatic Nitration
Scheme 2
Scheme 2. Late-Stage Electrophilic Aromatic Bromination with a Sulfide Catalyst
Scheme 3
Scheme 3. Late-Stage Electrophilic Aromatic Fluorination via a [PdIV]–F Species
Scheme 4
Scheme 4. Late-Stage Electrophilic Aromatic Oxygenation with Bis(methanesulfonyl) Peroxide
Scheme 5
Scheme 5. Late-Stage Aromatic C–H Bond Functionalization via Aryl Thianthrenium Salts
Scheme 6
Scheme 6. Enzyme-Catalyzed Late-Stage Functionalization of a C–H Bond
Scheme 7
Scheme 7. Vicarious Nucleophilic Substitution
Scheme 8
Scheme 8. Late-Stage Aromatic C–H Bond Functionalization via Pyridyl Phosphonium Salts
Scheme 9
Scheme 9. Functionalization of Indole Derivatives via Electrophilic Metalation
Scheme 10
Scheme 10. Palladium-Catalyzed Non-directed C–H Bond Functionalization Enabled by Ligand
Scheme 11
Scheme 11. Palladium-Catalyzed ortho C–H Bond Hydroxylation of Aryl Carboxylic Acids
Scheme 12
Scheme 12. Palladium-Catalyzed Remote C–H Bond Functionalization of Quinoline via Template
Scheme 13
Scheme 13. Ruthenium-Catalyzed Late-Stage Alkylation of C–H Bonds
Scheme 14
Scheme 14. Iridium-Catalyzed Late-Stage Borylation of C–H Bonds
Scheme 15
Scheme 15. Iron-Catalyzed Late-Stage HIE Reaction
Scheme 16
Scheme 16. Late-Stage Oxygenation of Arenes with Phthaloyl Peroxide
Scheme 17
Scheme 17. Late-Stage TEDAylation of Arenes
Scheme 18
Scheme 18. Late-Stage Electrochemical Trifluoromethylation of Hetarene with Zinc Sulfinate Reagents
Scheme 19
Scheme 19. Late-Stage Amination of Tyrosine via Photoredox Catalysis
Scheme 20
Scheme 20. Late-Stage Borylation of Arenes with Amine–Borane
Scheme 21
Scheme 21. Late-Stage Radio-fluorination Reaction of Aromatic C–H Bonds via Photoredox Catalysis
Scheme 22
Scheme 22. Late-Stage Hydroxylation of Aromatic C–H Bonds via Electrophotoredox Catalysis
See this image and copyright information in PMC

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