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Synlett 2025; 36(08): 1021-1028
DOI: 10.1055/a-2489-7403
letter

Synthesis of Indenoquinoxalinone-5-(furano, pyrano, and oxepino)spiro Ethers from Alkenylated Propargyl Ethers of Indenoquinoxalinone via Ring-Closing Enyne Metathesis

Ammundi Jayavel Chirranjeevi Padmashrija
a   Department of Chemistry, School of Advanced Sciences, Vellore Institute Technology, Vellore-632014, India
,
Sathananthan Kannadasan  ∗
a   Department of Chemistry, School of Advanced Sciences, Vellore Institute Technology, Vellore-632014, India
,
Ponnusamy Shanmugam  ∗
b   Organic and Bioorganic Chemistry Division, CSIR-Central Leather Research Institute (CLRI), Adyar, Chennai-600020, India
› Author AffiliationsA.J.C.P. thanks VIT, Vellore for the TRA fellowship and S. K. thanks VIT-SEED GRANT SG20230025.
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Abstract

A facile and efficient synthetic route for indenoquinoxalinone spiro-oxacyclic systems with small to medium ring sizes has been developed via an efficient ring-closing enyne metathesis (RCEYM) as a key step. The starting material O-alkylated propargylic alcohol of indenoquinoxalinone is synthesized via a two-step protocol: 1. propargylation of ketone followed by 2. alkenylation of the resulting propargyl ethers with alkenyl bromides. Upon being subjected to RCEYM using Grubbs II catalyst, the resulting O-alkenylated propargyl derivative furnished the spiro-ethereal products in good yield. Spectroscopic data and single-crystal XRD analysis characterized the structures of the products. A plausible mechanism is provided.

Key words

ring-closing enyne metathesis - indenoquinoxalinone - alkenyl ether - Grubbs II catalyst - oxacyclic spiro compounds

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-2489-7403.
  • Supporting Information


Publication History

Received: 24 October 2024

Accepted after revision: 26 November 2024

Accepted Manuscript online:
26 November 2024

Article published online:
07 January 2025

© 2024. Thieme. All rights reserved

Georg Thieme Verlag KG
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  • References and Notes

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  • 20 General Procedure for the Synthesis of O-Allylation of 11-(Arylethynyl)-11H-indeno[1,2-b]quinoxaline-11-ols 4a–k To an oven-dried 100 mL RBF fitted with a septum provided with nitrogen atmosphere were added 300 mg of synthesized 11-(arylethynyl)-11H-indeno[1,2-b] quinoxaline-11-ol (2a–k) dissolved in 5 mL DMF. Then sodium hydride (1.0 equiv.) was added at 0 °C and kept for stirring, maintaining the ice-cold condition throughout the reaction. After stirring for an hour, add allyl bromide using a syringe. Then, again, the reaction proceeded to stir for another hour. After this, the reaction was monitored using TLC to complete the reaction. On completion, ethyl acetate, followed by water, is slowly added to the reaction mixture. Then, the extracted organic layer was washed with a brine solution. After three washes, the combined organic layer was concentrated and purified using silica gel column chromatography. The O-allylated products were isolated with a 2–5% ethyl acetate/hexane solvent system.
  • 21 Spectroscopic Data for 11-(Allyloxy)-11-(Phenylethynyl)-11H-indeno[1,2-b]quinoxaline (4a) Colourless solid: yield 96%; mp 142–144 °C; Rf = 0.92 (25% EtOAc–hexane). FTIR (KBr): νmax = 3070, 2868, 2225, 1968, 1587, 1472, 1329, 1105, 1036, 958, 752, 687, 558, 489 cm–1. 1H NMR (400.3 MHz, CDCl3/TMS): δ = 8.22 (dd, J = 8.1, 1.5 Hz, 1 H), 8.19–8.12 (m, 2 H), 7.94 (dd, J = 6.2, 1.9 Hz, 1 H), 7.81–7.70 (m, 2 H), 7.68–7.57 (m, 2 H), 7.47 (dd, J = 7.8, 1.6 Hz, 2 H), 7.36–7.23 (m, 3 H), 5.96 (ddd, J = 16.2, 10.9, 5.7 Hz, 1 H), 5.25 (dd, J = 17.2, 1.5 Hz, 1 H), 5.11 (dd, J = 10.4, 1.3 Hz, 1 H), 4.61–4.48 (m, 2 H). 13C NMR (100.6 MHz, CDCl3/TMS): δ = 159.4, 153.5, 146.8, 143.1, 141.8, 136.6, 134.6, 132.6, 132.3, 130.9, 130.5, 130.3, 129.5, 129.4, 129.1, 128.4, 126.0, 122.6, 122.2, 117.5, 87.4, 85.6, 67.7 ppm. DEPT-135 (100.6 MHz, CDCl3/TMS): δ = 134.4 (+), 132.4 (+), 132.1 (+), 130.7 (+), 130.3 (+), 130.0 (+), 129.2 (+), 129.1 (+), 128.8 (+), 128.2 (+), 125.8 (+), 122.4 (+), 117.3 (–), 67.5 (–). HRMS (ESI): m/z calcd for C26H18N2O [M + H]: m/z calcd: 375.1497; found: 375.1498.
  • 22 General Procedure for RCEYM of Various O-Alkylated 11-(Arylethynyl)-11H-indeno[1,2-b]quinoxalin-11-ol 100 mg of the O-alkylated propargyl alcohol starting material (4a–k, 5a–c, and 6a–c; 1.0 equiv.) were taken in a 25 mL RBF and dissolved in 3 mL of toluene at 90 °C. Then, Grubbs II catalyst (20 mol%) was added, allowing the reaction to proceed for 12–48 h at the same temperature. The reaction was monitored using TLC. Then, the solvent was evaporated under reduced pressure. Then, the crude was purified using silica gel column chromatography. The products were isolated with 5–10% EtOAc–hexane.
  • 23 Spectroscopic Data for 3-{1-(p-Tolyl)vinyl)-5H-spiro[furan-2,11′-indeno[1,2-b]quinoxaline} (7b) Golden yellow liquid: yield 68%, Rf = 0.86 (25% EtOAc–hexane). FTIR (KBr): νmax = 2858, 1784, 1568, 1504, 1343, 1205, 1054, 912, 829, 751, 494 cm–1. 1H NMR (400.3 MHz, CDCl3/TMS): δ = 8.14–7.97 (m, 3 H), 7.68–7.57 (m, 2 H), 7.57–7.52 (m, 1 H), 7.52–7.44 (m, 2 H), 7.01 (d, J = 8.0 Hz, 2 H), 6.91 (d, J = 7.9 Hz, 2 H), 6.28 (s, 1 H), 5.24–5.09 (m, 1 H), 5.02 (dd, J = 14.2, 1.6 Hz, 1 H), 4.56 (s, 1 H), 4.15 (s, 1 H), 2.19 (s, 3 H) ppm. 13C NMR (100.6 MHz, CDCl3/TMS): δ = 161.7, 153.9, 147.8, 142.9, 142.0, 141.2, 140.9, 138.4, 137.3, 137.0, 132.3, 131.4, 130.4, 129.9, 129.8, 129.1, 128.9, 128.5, 128.2, 125.2, 122.4, 115.6, 93.2, 75.5, 21.0 ppm. DEPT-135 (100.6 MHz, CDCl3/TMS): δ = 132.3 (+), 131.4 (+), 130.4 (+), 129.9 (+), 129.8 (+), 129.1 (+), 128.9 (+), 128.5 (+), 128.2 (+), 125.2 (+), 122.4 (+), 115.6 (–), 75.5 (–), 21.0 (+). HRMS (ESI): m/z calcd for C27H20N2O [M + H]: m/z calcd: 389.1654; found: 389.1657.
  • 24 Spectroscopic Data for 3′-(1-Phenylvinyl)-5′,6′-dihydrospiro{indeno[1,2-b]quinoxaline-11,2′-pyran} (8a) Golden yellow liquid: 32%; Rf = 0.80 (25% EtOAc–hexane). FTIR (KBr): νmax = 3248, 1733, 1572, 1477, 1398, 1146, 1061, 994, 893, 769, 682, 581, 512 cm–1. 1H NMR (400.3 MHz, CDCl3/TMS): δ = 8.07–8.00 (m, 1 H), 7.96–7.86 (m, 2 H), 7.66–7.56 (m, 2 H), 7.52–7.46 (m, 1 H), 7.44–7.35 (m, 2 H), 6.83–6.65 (m, 5 H), 6.40 (dd, J = 5.4, 2.9 Hz, 1 H), 4.92–4.86 (m, 1 H), 4.59 (d, J = 1.4 Hz, 1 H), 4.50 (d, J = 1.2 Hz, 1 H), 4.06 (m, 1 H), 2.74–2.65 (m, 1 H), 2.52–2.39 (m, 1 H) ppm. 13C NMR (100.6 MHz, CDCl3/TMS): δ = 158.6, 154.4, 151.7, 148.6, 143.2, 142.5, 140.0, 134.4, 133.8, 133.1, 131.2, 131.0, 131.0, 130.0, 129.7, 129.4, 128.8, 126.8, 122.6, 121.1, 118.0, 76.7, 21.1 ppm. DEPT-135 (100.6 MHz, CDCl3/TMS): δ = 131.7 (+), 130.0 (+), 130.0 (+), 129.8 (+), 129.6 (+), 128.8 (+), 128.6 (+), 128.1 (+), 127.1 (+), 126.8 (+), 125.7 (+), 122.1 (+), 116.0 (–), 61.2 (–), 25.4 (–). HRMS (ESI): m/z calcd for C27H20N2O [M + H]: 389.1654; found: 389.1653.
  • 25 Spectroscopic Data for 3′-(1-{[1,1'-biphenyl]-4-yl}vinyl)-6′,7′-dihydro-5′H-spiro{indeno[1,2-b]quinoxaline-11,2′-oxepine} (9b) Golden yellow liquid: 57%; Rf = 0.88 (25% EtOAc–hexane). FTIR (KBr): νmax = 2872, 1765, 1577, 1481, 1329, 1205, 1109, 1063, 998, 838, 751, 696, 562, 507 cm–1. 1H NMR (400.3 MHz, CDCl3/TMS): δ = 7.95–7.86 (m, 2 H), 7.81 (d, J = 7.1 Hz, 1 H), 7.65 (d, J = 7.4 Hz, 1 H), 7.60–7.51 (m, 2 H), 7.45–7.34 (m, 3 H), 7.32–7.25 (m, 2 H), 7.25–7.16 (m, 2 H), 6.87 (d, J = 8.2 Hz, 2 H), 6.66 (d, J = 8.2 Hz, 2 H), 6.30 (dd, J = 7.5, 5.6 Hz, 1 H), 4.80–4.71 (m, 1 H), 4.63 (dd, J = 9.9, 1.5 Hz, 2 H), 4.04–3.95 (m, 1 H), 3.01–2.92 (m, 1 H), 2.68–2.62 (m, 1 H), 2.41–2.38 (m, 1 H), 2.19–2.03 (m, 1 H) ppm. 13C NMR (100.6 MHz, CDCl3/TMS): δ = 154.0, 149.8, 148.7, 142.3, 142.1, 141.0, 140.8, 139.7, 139.3, 136.5, 134.3, 131.6, 129.8, 129.7, 129.5, 128.8, 128.5, 127.9, 127.0, 126.9, 126.0, 125.7, 121.9, 115.6, 86.9, 28.4, 24.1 ppm. DEPT-135 (100.6 MHz, CDCl3/TMS): δ = 134.3 (+), 131.6 (+), 129.8 (+), 129.7 (+), 129.5 (+), 128.8 (+), 128.5 (+), 128.5 (+), 127.9 (+), 127.0 (+), 126.9 (+), 126.0 (+), 125.7 (+), 121.9 (+), 115.6 (–), 65.8 (–), 28.4 (–), 24.1 (–). HRMS (ESI): m/z calcd for C34H26N2O [M + H]: 479.2123; found: 479.2124.
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