Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 May 13;14(21):15167-15177.
doi: 10.1039/d4ra02206h. eCollection 2024 May 2.

Catalytic asymmetric carbenoid α-C-H insertion of ether

Xin Li  1 , San-Hong Yue  2 , Zi-Yang Tan  1 , Shu-Bo Liu  2 , De-Xiang Luo  1 , Ying-Jun Zhou  1 , Xiao-Wei Liang  2
Affiliations
Review

Catalytic asymmetric carbenoid α-C-H insertion of ether

Xin Li et al. RSC Adv. .

Abstract

Significant advancements have been made in catalytic asymmetric α-C-H bond functionalization of ethers via carbenoid insertion over the past decade. Effective asymmetric catalytic systems, featuring a range of chiral metal catalysts, have been established for the enantioselective synthesis of diverse ether substrates. This has led to the generation of various enantioenriched, highly functionalized oxygen-containing structural motifs, facilitating their application in the asymmetric synthesis of bioactive natural products.

PubMed Disclaimer

Conflict of interest statement

There are no conflicts to declare.

Figures

Fig. 1
Fig. 1. Representative bioactive nature products.
Fig. 2
Fig. 2. Representative catalysts for α-C–H bond carbenoid insertion of ether.
Scheme 1
Scheme 1. Enantioselectivity intramolecular C–H insertion reactions reported by Davises group.
Scheme 2
Scheme 2. Enantioselectivity intramolecular C–H insertion reactions reported by Hashimoto group.
Scheme 3
Scheme 3. Key step in natural product total synthesis reported by Hashimoto group and Wakimoto group.
Scheme 4
Scheme 4. Key steps in natural product total synthesis combining with chiral auxiliary and chiral rhodium strategy.
Scheme 5
Scheme 5. Enantioselective intramolecular C–H insertion reactions of donor–donor carbenoid and key step in total synthesis of E-δ-viniferin.
Scheme 6
Scheme 6. Key step in total synthesis of sophoraflavanone H by Kan group.
Scheme 7
Scheme 7. Chromanones and pyran synthesis via enantioselectivity intramolecular C–H insertion reactions.
Scheme 8
Scheme 8. Synthesis of β-lactones via iridium catalyzed asymmetric C–H insertion reactions by Che group.
Scheme 9
Scheme 9. Synthesis of β-lactones via rhodium catalyzed asymmetric C–H insertion reactions by Davies group.
Scheme 10
Scheme 10. Control reactions and proposal mechanism for Z-product formation by Davies group.
Scheme 11
Scheme 11. Enantioselective intermolecular C–H insertion reactions of donor–accepter carbenoid and THF by Davies group.
Scheme 12
Scheme 12. Enantioselective intermolecular C–H insertion reaction for the synthesis of thospermic acid core by Davies and Yu group.
Scheme 13
Scheme 13. Enantioselective intermolecular C–H insertion reaction for the synthesis of indoxamycin core by Sorensen group.
Scheme 14
Scheme 14. Enantioselective intermolecular C–H insertion reactions of donor–accepter carbenoid and silyl ether by Davies group.
Scheme 15
Scheme 15. Enantioselective intermolecular C–H insertion reactions of donor–accepter carbenoid and primary methine by Davies group.
Scheme 16
Scheme 16. Enantioselective intermolecular C–H insertion reactions of donor–accepter (TCE) carbenoid and primary methine by Davies group.
Scheme 17
Scheme 17. Enantioselective intermolecular C–H insertion reactions of donor–accepter carbenoid with chiral [RhBi] catalyst by Fürstner group.
Scheme 18
Scheme 18. Enantioselective intermolecular C–H insertion reactions with a scalable flow reactor by Davies and Jones group.
Scheme 19
Scheme 19. Enantioselective intermolecular C–H insertion reactions of donor–accepter carbenoid and THF catalyzed by copper complex.
Scheme 20
Scheme 20. Enantioselective intermolecular C–H insertion reactions of donor–accepter carbenoid and THF catalysed by iridium complex.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Docherty J. H. Lister T. M. Mcarthur G. Findlay M. T. Domingo-Legarda P. Kenyon J. Choudhary S. Larrosa I. Transition-metal-catalyzed C–H bond activation for the formation of C–C bonds in complex molecules. Chem. Rev. 2023;123:7692–7760. - PMC - PubMed
    2. Lapuh M. I. Mazeh S. Besset T. Chiral transient directing groups in transition-metal-catalyzed enantioselective C–H bond functionalization. ACS Catal. 2020;10:12898–12919.
    1. Santiago J. V. Machado A. H. L. Enantioselective carbenoid insertion into C(sp3)–H bonds. Beilstein J. Org. Chem. 2016;12:882–902. - PMC - PubMed
    2. Gandhi S. Catalytic enantioselective cross dehydrogenative coupling of sp3 C–H of heterocycles. Org. Biomol. Chem. 2019;17:9683. - PubMed
    3. Zhang S.-Y. Zhang F.-M. Tu Y.-Q. Direct Sp3 α-C–H activation and functionalization of alcohol and ether. Chem. Soc. Rev. 2011;40:1937–1949. - PubMed
    1. Silberrad O. Roy C. S. XXIV.—Gradual decomposition of ethyl diazoacetate. J. Chem. Soc., Trans. 1906;89:179–182.
    1. Yates P. The copper-catalyzed decomposition of diazoketones. J. Am. Chem. Soc. 1952;74:5376–5381.
    2. Scott L. T. DeCicco G. J. Intermolecular carbon-hydrogen insertion of copper carbenoids. J. Am. Chem. Soc. 1974;96:322–323.
    1. Doyle M. P. Duffy R. Ratnikov M. Zhou L. Catalytic carbene insertion into C–H bonds. Chem. Rev. 2010;110:704–724. - PubMed
    2. Bergstrom B. D. Nickerson L. A. Shaw J. T. Souza L. W. Transition metal catalyzed insertion reactions with donor/donor carbenes. Angew. Chem., Int. Ed. 2021;60:6864–6878. - PMC - PubMed