TMSCl-Catalyzed Aza-Diels-Alder Reaction: A Simple and Efficient ­Synthesis of Pyrano- and Furanoquinolines

Abstract

An efficient TMSCl-catalyzed synthesis of pyrano- and furanoquinolines and phenanthridinone derivative has been developed. In the presence of TMSCl (20 mol%), various aliphatic, ­aromatic and heteroaromatic aldehydes reacted with different anilines in the presence of either 2,3-dihydrofuran, 3,4-dihydro-2H-pyran or cyclohexenone to afford the aza-Diels-Alder adducts in excellent yield at room temperature. The ambient conditions, fast reaction rates, and excellent product yields are important characteristics of this reaction.

Key words

aza-Diels-Alder reaction - one-pot - TMSCl - pyrano- and furanoquinolines - excellent yields

References and Notes

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11

General Procedure for the Synthesis of Pyrano- and Furanoquinolines 8a and 8b.
A mixture of aldehyde 5 (1 mmol), aniline 6 (1.2 mmol), olefin 7 (1.2 mmol) and TMSCl (20 mol%) in MeCN (1 mL) was stirred at r.t. for an appropriate time (Table [2] ). After completion of the reaction (monitored by TLC), the reaction mixture diluted with EtOAc (25 mL) and washed with H₂O (2 × 20 mL) followed by brine (2 × 15 mL). The organic layer was dried over anhyd MgSO₄, followed by evaporation of solvent to obtain the crude product. Pure product 8 was obtained by flash column chromatography on silica gel using eluent (hexane-EtOAc, 95:5).
Synthesis of Pyranoquinolines 11a and 11b.
A mixture of aniline 2 (1 mmol), 3,4-dihydro-2H-pyran (3, 2.2 mmol) and TMSCl (20 mol%) in MeCN (1 mL) was stirred at r.t. for 3 h. The products were obtained as above.
Compound 8a from Table 2, Entry 17.
White solid, mp 108-110 °C. ¹H NMR (200 MHz, CDCl₃): δ = 1.78-1.81 (1 H, m), 2.30-2.33 (1 H, m), 2.80-2.83 (1 H, m), 3.78-3.81 (2 H, m), 3.96 (1 H, br s), 4.95 (1 H, d, J = 2.6 Hz), 5.25 (1 H, d, J = 7.6 Hz), 6.58 (1 H, d, J = 8.0 Hz), 6.84 (1 H, t, J = 7.4 Hz), 7.04-7.06 (3 H, m), 7.24 (1 H, d, J = 5.2 Hz), 7.34 (1 H, d, J = 7.2 Hz). ¹³C NMR (50 MHz, CDCl₃): δ = 145.36, 144.30, 129.97, 128.26, 126.53, 124.12, 123.95, 122.61, 119.45, 114.85, 75.61, 66.50, 53.53, 45.85, 25.07. MS (70 eV): m/z (%) = 258 (8) [M + 1]⁺, 257 (55) [M⁺], 212 (100), 178 (25), 130 (23), 115 (22), 91 (25), 77 (28). HRMS: m/z calcd for C₁₅H₁₅NOS: 257.0874; found: 257.0869.
Compound 8b from Table 2, Entry 17.
White solid, mp 146-148 °C. ¹H NMR (200 MHz, CDCl₃): δ = 1.86-1.89 (1 H, m), 2.12-2.16 (1 H, m), 2.45-2.48 (1 H, m), 3.85-3.89 (1 H, m), 4.04-4.08 (1 H, m), 4.14 (1 H, d, J = 11.0 Hz), 4.31 (1 H, br s), 4.60 (1 H, d, J = 4.6 Hz), 6.65 (1 H, d, J = 8.0 Hz), 6.84 (1 H, t, J = 7.4 Hz), 6.99-7.16 (3 H, m), 7.29-7.40 (2 H, m). ¹³C NMR (50 MHz, CDCl₃): δ = 145.34, 144.63, 131.07, 128.90, 126.41, 125.80, 125.27, 120.05, 118.75, 114.79, 76.02, 65.15, 53.47, 44.72, 29.03.
Compound 8a from Table 2, Entry 18. White solid, mp 155-156 °C. ¹H NMR (200 MHz, CDCl₃): δ = 1.55-1.58 (4 H, m), 2.18-2.22 (1 H, m), 3.40-3.43 (1 H, m), 3.55-3.59 (1 H, m), 4.11-4.14 (1 H, m), 4.96 (1 H, d, J = 2.6 Hz), 5.29 (1 H, d, J = 5.6 Hz), 6.10 (1 H, d, J = 8.2 Hz), 6.84 (1 H, t, J = 7.4 Hz), 7.03-7.08 (3 H, m), 7.23 (1 H, d, J = 3.4 Hz), 7.43 (1 H, d, J = 7.6 Hz). ¹³C NMR (50 MHz, CDCl₃): δ = 144.33, 144.28, 127.75, 127.29, 126.41, 123.61, 123.50, 119.84, 118.46, 114.27, 60.32, 55.35, 39.31, 25.07, 18.12. MS (70 eV): m/z (%) = 272 (5) [M + 1]⁺, 271 (28) [M⁺], 212 (100), 178 (20), 130 (22), 91 (20), 77 (22), 70 (24). HRMS: m/z calcd for C₁₆H₁₇NOS: 271.1031; found: 271.1025.
Compound 8b from Table 2, Entry 18.
White solid, mp 135-137 °C. ¹H NMR (200 MHz, CDCl₃): δ = 1.35-1.37 (1 H, m), 1.61-1.83 (3 H, m), 2.02-2.06 (1 H, m), 3.70 (1 H, t), 4.07 (1 H, d, J = 9.8 Hz), 4.37 (1 H, d, J = 2.6 Hz), 5.03 (1 H, d, J = 10.6 Hz), 6.52 (1 H, d, J = 8.2 Hz), 6.73 (1 H, t, J = 7.4 Hz), 6.95-6.97 (3 H, m), 7.21-7.24 (2 H, m). ¹³C NMR (50 MHz, CDCl₃): δ = 146.04, 144.01, 130.70, 129.21, 126.25, 125.27, 124.89, 120.67, 117.79, 114.24, 68.64, 50.58, 40.12, 24.05, 21.80.
Compound 8a from Table 2, Entry 19. Pale yellow solid, mp 75-77 °C. ¹H NMR (200 MHz, CDCl₃): δ = 1.85-1.88 (1 H, m), 2.22-2.26 (1 H, m), 2.96-2.99 (1 H, m), 3.78-3.82 (2 H, m), 3.89 (1 H, br s), 4.69 (1 H, d, J = 3.0 Hz), 5.23 (1 H, d, J = 7.6 Hz), 6.26-6.36 (2 H, m), 6.60 (1 H, d, J = 8.0 Hz), 6.83 (1 H, t, J = 7.2 Hz), 7.10 (1 H, t, J = 7.6 Hz), 7.36-7.39 (2 H, m). ¹³C NMR (50 MHz, CDCl₃): δ = 154.80, 144.34, 141.60, 130.05, 128.31, 122.58, 119.31, 114.82, 110.19, 105.63, 75.36, 66.42, 51.48, 42.24, 25.25. MS (70 eV): m/z (%) = 242 (9) [M + 1⁺], 241 (55) [M⁺], 196 (100), 178 (25), 167 (25), 130 (22), 91 (18), 77 (27). HRMS: m/z calcd for C₁₅H₁₅NO₂: 241.1103; found: 241.1097.
Compound 8b from Table 2, Entry 19.
Pale yellow solid, mp 62-64 °C. ¹H NMR (200 MHz, CDCl₃): δ = 1.83-1.86 (1 H, m), 2.12-2.16 (1 H, m), 2.63-2.65 (1 H, m), 3.84-3.87 (1 H, m), 4.01-4.05 (2 H, m), 4.29 (1 H, br s), 4.61 (1 H, d, J = 5.0 Hz), 6.34-6.38 (2 H, m), 6.63 (1 H, d, J = 8.0 Hz), 6.80 (1 H, t, J = 7.2 Hz), 7.13 (1 H, t, J = 7.2 Hz), 7.40-7.43 (2 H, m). ¹³C NMR (50 MHz, CDCl₃): δ = 154.50, 144.40, 142.27, 130.97, 128.84, 119.99, 118.59, 114.85, 110.17, 107.41, 75.72, 65.21, 51.08, 40.66, 29.10.
Compound 8a from Table 2, Entry 20.
Brown solid, mp 151-152 °C. ¹H NMR (200 MHz, CDCl₃): δ = 1.44-1.60 (4 H, m), 2.30-2.40 (1 H, m), 3.40-3.51 (2 H, m), 3.89-4.02 (1 H, m), 4.71 (1 H, d, J = 2.3 Hz), 5.25 (1 H, d, J = 5.6 Hz), 6.29-6.32 (1 H, m), 6.36-6.40 (1 H, m), 6.62 (1 H, d, J = 8.0 Hz), 6.83 (1 H, t, J = 6.6 Hz), 7.08 (1 H, t, J = 6.4 Hz), 7.43 (2 H, d, J = 8.6 Hz). ¹³C NMR (50 MHz, CDCl₃): δ = 154.03, 144.40, 141.60, 128.09, 127.69, 120.08, 118.59, 114.50, 110.16, 105.98, 71.80, 60.65, 53.74, 36.22, 25.28, 18.76. MS (70 eV): m/z (%) = 256 (7) [M + 1⁺], 255 (42) [M⁺], 196 (100), 167 (23), 130 (33), 91 (15), 81 (24), 77 (25), 70 (20). HRMS: m/z calcd for C₁₆H₁₇NO₂: 255.1259; found: 255.1254.
Compound 8b from Table 2, Entry 20.
Pale brown solid, mp 92-94 °C. ¹H NMR (200 MHz, CDCl₃): δ = 1.40-1.43 (1 H, m), 1.51-1.54 (1 H, m), 1.74-1.78 (2 H, m), 2.20-2.24 (1 H, m), 3.64-3.69 (1 H, m), 4.01-4.05 (1 H, m), 4.40 (1 H, d, J = 3.0 Hz), 4.81 (1 H, d, J = 10.6 Hz), 6.31-6.35 (2 H, m), 6.53 (1 H, d, J = 8.0 Hz), 6.69 (1 H, t, J = 7.4 Hz), 7.06 (1 H, t, J = 7.6 Hz), 7.21 (1 H, d, J = 7.6 Hz), 7.38 (1 H, s). ¹³C NMR (50 MHz, CDCl₃): δ = 155.01, 143.97, 142.00, 130.46, 129.09, 120.45, 117.64, 114.33, 110.04, 107.32, 73.89, 67.90, 48.84, 36.96, 24.18, 22.03.
Compound 8a from Table 2, Entry 23. Pale yellow solid, mp 170-172 °C. ¹H NMR (200 MHz, CDCl₃): δ = 0.92-0.96 (2 H, m), 1.19-1.29 (3 H, m), 1.40-1.50 (3 H, m), 1.58-1.65 (1 H, m), 1.67-1.71 (2 H, m), 1.76-1.83 (3 H, m), 1.90-1.93 (1 H, m), 2.18-2.22 (1 H, m), 2.97 (1 H, dd, J = 7.6, 2.0 Hz), 3.38-3.45 (1 H, m), 3.56-3.60 (1 H, m), 5.02 (1 H, d, J = 5.5 Hz), 6.51 (1 H, d, J = 8.0 Hz), 6.72 (1 H, t, J = 7.3 Hz), 7.03 (1 H, t, J = 7.1 Hz), 7.36 (1 H, d, J = 7.6 Hz). ¹³C NMR (50 MHz, CDCl₃): δ = 144.95, 127.81, 127.40, 120.06, 117.68, 113.91, 72.56, 60.58, 59.15, 37.45, 33.15, 30.20, 28.46, 26.27, 25.90, 25.83, 25.52, 17.93.
Compound 8b from Table 2, Entry 23. Pale yellow solid, mp 115-117 °C. ¹H NMR (200 MHz, CDCl₃): δ = 1.13-1.20 (5 H, m), 1.49-1.53 (2 H, m), 1.64-1.84 (8 H, m), 1.95-1.97 (1 H, m), 3.23-3.27 (1 H, m), 3.63-3.69 (1 H, m), 3.83-3.87 (1 H, m), 4.50 (1 H, d, J = 3.5 Hz), 6.51 (1 H, d, J = 8.0 Hz), 6.64 (1 H, t, J = 7.8 Hz), 7.04 (1 H, t, J = 7.8 Hz), 7.24 (1 H, d, J = 7.2 Hz). ¹³C NMR (50 MHz, CDCl₃): δ = 144.85, 129.71, 128.73, 119.91, 116.78, 114.05, 73.35, 66.12, 55.60, 38.61, 33.22, 30.23, 26.81, 26.71, 26.56, 26.28, 24.18, 23.35.