Unusual Transformations of Cyclic Allenes with an Enamine Moiety into Complex Frameworks

Abstract

The thermolysis reactions of benzoazacyclodecatrienes under microwave irradiation conditions in toluene at 150 °C afforded complex azabenzo[a]cyclopropa[cd]azulene and (epiminomethano)cyclopenta[a]indene frameworks. Cyclopropanes were established as intermediates of the ultimate thermolysis products.

Key words

thermal transformation - azacyclic allene - cyclopropanes - epiminomethanocyclopentaindenes - microwave-assisted reaction - polyheterocyclic compounds

• References and Notes

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• 13 Methyl 8-Isopropyl-10,11-dimethoxy-3-methyl-6-phenyl-3-azabenzo[d]cyclodeca-4,6,7-triene-5-carboxylate (4b) Colorless crystals; yield: 438 mg (92%); mp 175–176 °C; R_f  = 0.44 (EtOAc–hexane, 1:2). IR (KBr): 1956, 1055 (C=C=C), 1684 (С=O) cm^–1. ¹H NMR (600 MHz, CDCl₃): δ = 7.61 (s, 1 H), 7.33–7.30 (m, 2 H), 7.25–7.23 (m, 2 H), 7.14–7.12 (m, 1 H), 6.88 (s, 1 H), 6.59 (s, 1 H), 4.18–4.14 (m, 1 H), 3.91 (s, 3 H), 3.85 (s, 3 H), 3.61 (s, 3 H), 3.50–3.46 (m, 1 H), 3.16 (s, 3 H), 2.94 (sept, J = 6.7, 1 H), 2.81–2.70 (m, 2 H), 1.35 (d, J = 6.7 Hz, 3 H), 1.02 (d, J = 6.7 Hz, 3 H). ¹³C NMR (150 MHz, CDCl₃): δ = 206.0, 170.7, 147.9, 147.6, 147.4, 138.3, 129.3, 128.7, 128.2 (2 C), 126.3, 125.7 (2 C), 112.9, 111.5, 110.5, 103.5, 96.0, 56.1, 55.9, 51.8, 51.1, 45.1, 31.7, 31.0, 22.2, 21.2. LC-MS (ESI): m/z = 434 [M + H]⁺. Anal. Calcd for C₂₇H₃₁NO₄: C, 74.80; H, 7.21; N, 3.23. Found: C, 74.95; H, 7.41; N, 3.37.
• 14 Methyl 10,11-Dimethoxy-3-methyl-6,8-diphenyl-3-azabenzo[d]cyclodeca-4,6,7-triene-5-carboxylate (4d) Colorless crystals; yield: 473 mg (92%); mp 210–212 °C. R_f  = 0.47 (EtOAc–hexane, 1:1). IR (KBr): 1947, 1059 (C=C=C), 1690 (С=O) cm^–1. ¹H NMR (600 MHz, DMSO-d ₆): δ = 7.58 (s, 1 H), 7.42–7.38 (m, 4 H), 7.34–7.29 (m, 5 H), 7.22–7.20 (m, 1 H), 6.93 (s, 1 H), 6.70 (s, 1 H), 3.89–3.85 (m, 1 H), 3.76 (s, 3 H), 3.61 (s, 3 H), 3.47 (s, 3 H), 3.29–3.25 (m, 1 H), 3.17 (s, 3 H), 3.07–3.02 (m, 1 H), 2.98–2.92 (m, 1 H). ¹³C NMR (150 MHz, DMSO-d ₆): δ = 209.1, 168.4, 148.1, 147.7, 147.2, 137.4, 136.5, 129.5, 128.8 (2 C), 128.7 (2 C), 127.4, 127.3 (2 C), 127.1, 125.9, 125.5 (2 C), 113.7, 112.8, 107.0, 104.7, 93.1, 55.6, 55.5, 50.9, 50.7, 44.6, 30.2. LC-MS (ESI): m/z = 468 [M + H]⁺. Anal. Calcd for C₃₀H₂₉NO₄: C, 77.06; H, 6.25; N, 3.00. Found: C, 77.19; H, 6.33; N, 3.13.
• 15 General Procedure A A solution of the appropriate allene derivative (0.68 mmol) in dry toluene (6.0 mL) was placed in a microwave reactor and heated at 150 °C for 30 min while the progress of the reaction was monitored by TLC [EtOAc–hexane, 1:1 (4a and 4c); EtOAc–hexane, 1:2 (4b, 4d, and 4e)]. The solvent was evaporated in vacuo. Products 7a–c, 7e, and 8a–e were isolated by chromatography on silica gel; compounds 7a and 7c, 7b and 8b, 7e, 8a, 8c, and 8e were eluted with EtOAc–hexane (1:3, 1:5, 1:12, 1:2, 1:1, and 1:10, respectively).
• 16 General Procedure B A solution of the appropriate allene derivative (0.16 mmol) in dry toluene (6.0 mL) was irradiated in a microwave reactor at 150 °C for 3–7.5 h with stirring while the progress of the reaction was monitored by TLC [EtOAc–hexane, 1:1 (4a and 4c); EtOAc–hexane, 1:2, (4b, 4d, and 4e)]. The solvent was evaporated in vacuo and products 8a–e were crystallized from Et₂O.
• 17 Methyl 6,7-Dimethoxy-2,4b-dimethyl-4a-phenyl-1,2,4a,4b,8b,8c-hexahydro-2-azabenzo[a]cyclopropa[cd]azulene-4-carboxylate (7a) Colorless crystals; yield: 162 mg (59%) (Procedure A); mp 153–155 °C. R_f  = 0.47 (EtOAc–hexane, 1:1). IR (KBr): 1682 (C=O) cm^–1. ¹H NMR (600 MHz, CDCl₃): δ = 7.57–7.56 (m, 2 H), 7.26–7.24 (m, 2 H), 7.15–7.13 (m, 1 H), 6.87 (s, 1 H), 6.74 (s, 1 H), 6.50 (s, 1 H), 4.22 (dd, J = 14.1, 1.5 Hz, 1 H), 3.88 (s, 3 H), 3.85 (s, 3 H), 3.77–3.75 (m, 1 H), 3.58 (dd, J = 14.1, 5.6 Hz, 1 H), 3.44 (s, 3 H), 3.00 (s, 3 H), 2.12 (d, J = 6.6 Hz, 1 H), 1.71 (s, 3 H). ¹³C NMR (150 MHz, CDCl₃): δ = 168.7, 147.5, 147.4, 146.7, 144.1, 140.1, 134.6, 131.1 (2 C), 127.3 (2 C), 125.3, 107.5, 106.8, 98.0, 55.8, 55.6, 51.4, 49.8, 46.5, 42.1, 39.1, 37.8, 37.0, 16.2. LC-MS (ESI): m/z = 406 [M + H]⁺. Anal. Calcd for C₂₅H₂₇NO₄: C, 74.05; H, 6.71; N 3.45. Found: C, 74.21; H, 6.86; N, 3.55. Methyl 5,6-Dimethoxy-2,11-dimethyl-14-phenyl-11-azatetracyclo[7.5.0.0^2,12.0^3,8]tetradeca-3,5,7,13-tetraene-13-carboxylate (8a) Colorless crystals; yield: 32 mg (50%) (Procedure B); 3 mg (1%) (Procedure A); mp 149–151 °C. R_f  = 0.52 (EtOAc–hexane, 1:1). IR (KBr): 1694 (C=O) cm^–1. ¹H NMR (600 MHz, CDCl₃): δ = 7.49–7.47 (m, 2 H), 7.41–7.35 (m, 3 H), 6.74 (s, 1 H), 6.73 (s, 1 H), 3.92 (s, 3 H), 3.89 (s, 3 H), 3.70 (s, 3 H), 3.68 (d, J = 1.7 Hz, 1 H), 3.23 (d, J = 4.1 Hz, 1 H), 3.12–3.11 (m, 1 H), 2.66 (dd, J = 10.7, 2.5 Hz, 1 H), 2.48 (dd, J = 10.7, 2.5 Hz, 1 H), 2.22 (s, 3 H), 1.48 (s, 3 H). ¹³C NMR (150 MHz, CDCl₃): δ = 166.3, 151.1, 148.3, 147.8, 137.3, 137.1, 135.1, 128.5, 128.0 (2 C), 127.9 (2 C), 124.9, 107.1, 106.9, 72.8, 67.9, 59.6, 55.8, 55.7, 51.2, 51.1, 42.6, 42.3, 18.3. LC-MS (ESI): m/z = 406 [M + H]⁺. Anal. Calcd for C₂₅H₂₇NO₄: C, 74.05; H, 6.71; N, 3.45. Found: C, 74.28; H, 6.91; N, 3.56.
• 18 CCDC 1830405 and CCDC 1579823 contain the supplementary crystallographic data for compounds 7a and 8a, respectively. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
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• 23 General Procedure C A solution of compound 7a (0.24 mmol) in absolute toluene (6.0 mL) was irradiated in a microwave reactor at 150 °C for 2 h with stirring while the progress of the reaction was monitored by TLC (EtOAc–hexane, 1:1). The solvent was then evaporated in vacuo and product 8a was crystallized from Et₂O; yield: 49 mg (50%).
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