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. 2025 Jan;14(1):e202400421.
doi: 10.1002/ajoc.202400421. Epub 2024 Nov 19.

One-Pot Synthesis of 2-Substituted Indoles and 7-Azaindoles via Sequential Alkynylation and Cyclization of 2-Iodo- N-mesylarylamines and Alkynes in the Presence of Cu2O

Ahmed R Ali  1   2 , Longqin Hu  1   3
Affiliations

One-Pot Synthesis of 2-Substituted Indoles and 7-Azaindoles via Sequential Alkynylation and Cyclization of 2-Iodo- N-mesylarylamines and Alkynes in the Presence of Cu2O

Ahmed R Ali et al. Asian J Org Chem. 2025 Jan.

Abstract

A one-pot process was developed to synthesize in moderate to high yield a series of 2-substituted indoles and 7-azaindoles starting from 2-iodo-N-mesylarylamines and terminal alkynes in the presence of Cu2O in DMF at 90-120 °C. Without isolation of any intermediate, our optimized conditions enabled the introduction of ester, phenyl, hydroxymethyl, hydroxyethyl, N-Boc-aminomethyl, and methyl at the 2-postion of indoles and 7-azaindoles. The reaction tolerates a variety of substrates containing halogens, or acid- or base-sensitive functional groups without requiring a Pd catalyst, a ligand, or a base.

Keywords: 5-endo-dig; 7-azaindoles; Castro-Stephens; alkynes; indoles.

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Figures

Scheme 1.
Scheme 1.
Proposed reaction mechanism.
Scheme 2.
Scheme 2.
Control reactions.
See this image and copyright information in PMC

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References

    1. Saxton JE, Nat. Prod. Rep 1995, 12, 385–411; - PubMed
    2. Saxton JE, Nat. Prod. Rep 1994, 11, 493–531; - PubMed
    3. Chadha N, Silakari O, Eur. J. Med. Chem 2017, 134, 159–184; - PubMed
    4. Van Order RB, Lindwall HG, Chem. Rev 2002, 30, 69–96;
    5. Ma YM, Liang XA, Kong Y, Jia B, Agric J. Food Chem. 2016, 64, 6659–6671; - PubMed
    6. Kaushik NK, Kaushik N, Attri P, Kumar N, Kim CH, Verma AK, Choi EH, Molecules 2013, 18, 6620–6662; - PMC - PubMed
    7. Homer JA, Sperry J, J. Nat. Prod 2017, 80, 2178–2187; - PubMed
    8. Kumari A, Singh RK, Bioorg. Chem 2019, 89, 103021. - PubMed
    1. Chen D, Chen Y, Ma Z, Zou L, Li J, Liu Y, J. Org. Chem 2018, 83, 6805–6814; - PubMed
    2. Chen X, Qiu G, Liu R, Chen D, Chen Z, Org. Chem. Front 2020, 7, 890–895;
    3. Ganesan B, Senadi GC, Guo B-C, Hung M-Y, Lin W-Y, RSC Adv. 2018, 8, 40968–40973; - PMC - PubMed
    4. Ling F, Song D, Chen L, Liu T, Yu M, Ma Y, Xiao L, Xu M, Zhong W, J. Org. Chem 2020, 85, 3224–3233; - PubMed
    5. Peng H, Jiang K, Zhen G, Wang F, Yin B, RSC Adv. 2020, 10, 11750–11754; - PMC - PubMed
    6. Yuan S, Zhang DQ, Zhang JY, Yu B, Liu HM, Org. Lett 2020, 22, 814–817; - PubMed
    7. Zhang AA, Meng T, Wang W, Liu X, Zhu Y, Liu L, Appl. Organomet.Chem 2020, 34, e5513;
    8. Zhang BS, Li Y, Zhang Z, An Y, Wen YH, Gou XY, Quan SQ, Wang XG, Liang YM, J. Am. Chem. Soc 2019, 141, 9731–9738; - PubMed
    9. Zhao G, Roudaut C, Gandon V, Alami M, Provot O, Green Chem. 2019, 21, 4204–4210.
    1. Cacchi S, Fabrizi G, Chem. Rev 2005, 105, 2873–2920; - PubMed
    2. Humphrey GR, Kuethe JT, Chem. Rev 2006, 106, 2875–2911; - PubMed
    3. Newman SG, Lautens M, J. Am. Chem. Soc 2010, 132, 11416–11417; - PubMed
    4. Bugaenko DI, Karchava AV, Yurovskaya MA, Russ. Chem. Rev 2019, 88, 99–159;
    5. Yu Y, Zhong JS, Xu K, Yuan Y, Ye KY, Adv. Synth. Catal 2020;
    6. Neto JSS, Zeni G, Org. Chem. Front 2020, 7, 155–210.
    1. Larock RC, Yum EK, J. Am. Chem. Soc 1991, 113, 6689–6690.
    1. Tao SW, Zhou JY, Liu RQ, Zhu YM, J. Org. Chem 2019, 84, 8121–8130; - PubMed
    2. Politanskaya L, Petyuk M, Tretyakov E, J. Fluor. Chem 2019, 228.

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