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
. 2020 Jun 30;10(42):24830-24839.
doi: 10.1039/d0ra04592f. eCollection 2020 Jun 29.

Copper(ii)-catalyzed synthesis of multisubstituted indoles through sequential Chan-Lam and cross-dehydrogenative coupling reactions

Xin Chen  1   2 , Yunyun Bian  1 , Baichuan Mo  1   2 , Peng Sun  1   2 , Chunxia Chen  1   2 , Jinsong Peng  1
Affiliations

Copper(ii)-catalyzed synthesis of multisubstituted indoles through sequential Chan-Lam and cross-dehydrogenative coupling reactions

Xin Chen et al. RSC Adv. .

Abstract

Starting from arylboronic acids and ester (Z)-3-aminoacrylates, one-pot syntheses of diverse indole-3-carboxylic esters have been described through copper(ii)-catalyzed sequential Chan-Lam N-arylation and cross-dehydrogenative coupling (CDC) reactions. The initial Chan-Lam arylation can proceed in DMF at 100 °C for 24 h to give ester (Z)-3-(arylamino)acrylate intermediates in the presence of Cu(OAc)2/tri-tert-butylphosphine tetrafluoroborate, a catalytic amount of myristic acid as the additive, KMnO4 and KHCO3. Sequentially, these in situ arylated intermediates can undergo an intramolecular oxidative cross-dehydrogenative coupling process in mixed solvents (DMF/DMSO = 2 : 1) at 130 °C to give C3-functionalized multi-substituted indole derivatives.

PubMed Disclaimer

Conflict of interest statement

There are no conflicts to declare.

Figures

Scheme 1
Scheme 1. Metal-catalyzed indole syntheses based on the N-arylated enamines and imines.
Scheme 2
Scheme 2. Prospected sequence for the synthesis of indoles.
Scheme 3
Scheme 3. Effect of ligands on the copper-catalyzed annulations reaction. a Reaction conditions: 20 mol% Cu(OAc)2, KHCO3, DMF, air, 70 °C, 24 h; isolated yields. b PCy3 was directly used.
Fig. 1
Fig. 1. Unsuccessful enamine substrates.
Scheme 4
Scheme 4. Proposed catalytic pathway for the formation of indole 3.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Kochanowska-Karamyan A. J. Hamann M. T. Chem. Rev. 2010;110:4489. doi: 10.1021/cr900211p. - DOI - PMC - PubMed
    1. Do-Thanh C.-L. Vargas J. J. Thomas J. W. Armel G. R. Best M. D. J. Agric. Food Chem. 2016;64:3533. doi: 10.1021/acs.jafc.6b00675. - DOI - PubMed
    1. Vitaku E. Smith D. T. Njardarson J. T. J. Med. Chem. 2014;57:10257. doi: 10.1021/jm501100b. - DOI - PubMed
    2. Chadha N. Silakari O. Eur. J. Med. Chem. 2017;134:159. doi: 10.1016/j.ejmech.2017.04.003. - DOI - PubMed
    1. Liu Y. Ai K. Lu L. Chem. Rev. 2014;114:5057. doi: 10.1021/cr400407a. - DOI - PubMed
    2. Vlasselaer M. Dehaen W. Molecules. 2016;21:785. doi: 10.3390/molecules21060785. - DOI - PMC - PubMed
    1. de Sa Alves F. R. Barreiro E. J. Fraga C. A. M. Mini-Rev. Med. Chem. 2009;9:782. doi: 10.2174/138955709788452649. - DOI - PubMed
    2. Sravanthi T. V. Manju S. L. Eur. J. Pharm. Sci. 2016;91:1. doi: 10.1016/j.ejps.2016.05.025. - DOI - PubMed
    3. Kaushik N. K. Kaushik N. Attri P. Kumar N. Kim C. H. Verma A. K. Choi E. H. Molecules. 2013;18:6620. doi: 10.3390/molecules18066620. - DOI - PMC - PubMed
    4. Singh T. P. Singh O. M. Mini-Rev. Med. Chem. 2018;18:9. doi: 10.2174/1389557517666170807124507. - DOI - PubMed