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; Sathananthan Kannadasan; Ponnusamy Shanmugam

doi:10.1055/a-2489-7403

Synlett, Table of Contents

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

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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

^aDepartment of Chemistry, School of Advanced Sciences, Vellore Institute Technology, Vellore-632014, India

,

Sathananthan Kannadasan ∗

^aDepartment of Chemistry, School of Advanced Sciences, Vellore Institute Technology, Vellore-632014, India

,

Ponnusamy Shanmugam ∗

^bOrganic and Bioorganic Chemistry Division, CSIR-Central Leather Research Institute (CLRI), Adyar, Chennai-600020, India

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Abstract

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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

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References

References and Notes
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19 CCDC 2332970 (2a) and CCDC 2335193 (4b) contain the supplementary crystallographic data for this paper. The data are provided free of charge by the joint Cambridge Crystallographic Data Centre and FIZ Karlsruhe online deposition service via. www.ccdc.cam.ac.uk/structures
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; R_f = 0.92 (25% EtOAc–hexane). FTIR (KBr): ν_max = 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%, R_f = 0.86 (25% EtOAc–hexane). FTIR (KBr): ν_max = 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%; R_f = 0.80 (25% EtOAc–hexane). FTIR (KBr): ν_max = 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%; R_f = 0.88 (25% EtOAc–hexane). FTIR (KBr): ν_max = 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.
26 Kavitha Preethi R, Kannadasan S, Shanmugam P. Tetrahedron Lett. 2023; 120: 154448

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