A New Way to 2-Methylbenzo- and Pyridoindoles

Abstract

Allyltriphenylphosphonium chloride reacts with some 1-nitronaphthalene and 5-nitroquinoline derivatives in the presence of Ti(i-PrO)₄ and DBU to give 1-hydroxyindoles, which can be reduced in situ to the corresponding indoles.

cyclizations - heterocycles - indoles - nucleophilic additions - ylides

References

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Standard procedure: To the slurry of 1 (2.5 mmol) and 2 (1 g, 3 mmol) in dry HMPA (2.5 mL), Ti(i-PrO)₄ (1.85 mL, 6.25 mmol) was added followed by the addition of DBU (1.9 mL, 12.5 mol). The slurry was stirred at room temperature for the time specified in the table until HPLC analysis showed complete conversion of the substrate. At this point MeOH (5 mL) was added followed by Et₃N (1 mL) and then ethyl bromoacetate (330 µL, 3 mmol), and the mixture stirred further until HPLC analysis showed complete conversion. Then, the mixture was diluted with ethyl acetate and ca. 5 mL of sat aq NH₄Cl solution was added. The mixture was stirred for 20 min, filtered through a Celite pad, diluted with water, extracted with ethyl acetate and chromatographed. Selected spectral data (¹H NMR: 400 MHz, CDCl₃; Ms: 70 eV): 3a: δ_H = 2.37 (s, 3 H), 6.01 (broad s, 1 H), 6.88-6.94 (m, 1 H), 7.17 (ddd, J = 8.0 Hz, 6.8 Hz, 1.1 Hz, 1 H), 7.26-7.30 (m, 1 H), 7.40 (d, J = 8.4 Hz, 1 H), 7.72 (d, J = 8.0 Hz, 1 H), 8.34 (d, J = 8.4 Hz, 1 H), 8.69 (broad s, 1 H); HRMS: 197.0847; calcd. for C₁₃H₁₁ON: 197.0841; (¹H NMR: 500 MHz, CDCl₃; MS: 70 eV): 4a:
δ_H = 2.50 (d, J = 0.9, 3 H), 6.34-6.37 (m, 1 H), 7.36 (ddd, J = 8.2 Hz, 6.9 Hz, 1.3 Hz, 1 H), 7.46 (d, J = 8.5 Hz, 1 H overlapped on ddd, J = 8.3 Hz, 7.0 Hz, 1.3 Hz, 1 H), 7.61 (dd, J = 8.5 Hz, 0.9 Hz, 1 H), 7.87-7.88 (m, 1 H), 7.89-7.90 (m, 1 H), 8.51 (broad s, 1 H); δ_C = 132.99, 130.11, 129.89, 128.87, 125.22, 124.85, 123.20, 121.34, 120.37, 120.22, 119.00, 102.18, 13.73; HRMS: 181.0895; calcd. for C₁₃H₁₁N: 181.0892; 4b: δ_H = 1.29 (s, 9 H), 2.53 (d, J = 0.8 Hz, 3 H), 6.35-6.36 (m, 1 H), 7.45 (ddd, J = 8.2 Hz, 6.8 Hz, 1.3 Hz, 1 H), 7.50 (ddd, J = 8.2 Hz, 6.8 Hz, 1.3 Hz, 1 H), 7.90-7.92 (m, 1 H), 8.00 (s, 1 H), 8.60 (br s, 1 H), 8.82-8.84 (m, 1 H); δ_C = 133.47, 132.58, 132.41, 131.31, 128.82, 125.37, 124.36, 123.56, 121.79, 121.44, 119.15, 47.03, 31.20, 13.71; HRMS: 269.1246; calcd. for C₁₇H₁₉NS: 269.1238; 4c: δ_H = 2.48 (d, J = 0.8 Hz, 3 H), 3.99 (s, 3 H), 6.26-6.27 (m, 1 H), 6.96 (s, 1 H), 7.37 (ddd, J = 8.2 Hz, 6.9 Hz, 1.2 Hz, 1 H), 7.48 (ddd, J = 8.2 Hz, 6.9 Hz, 1.2 Hz, 1 H), 7.80-7.81 (m, 1 H), 8.28-8.29 (m, 1 H), 8.36 (br s, 1 H);
δ_C = 150.18, 132.92, 125.92, 125.16, 124.11, 123.34, 122.88, 122.71, 121.85, 118.82, 102.04, 97.99, 55.82, 13.73; HRMS: 211.0998; calcd. for C₁₄H₁₃NO: 211.0997; 4d: δ_H = 2.55 (d, J = 0.8 Hz, 3 H), 6.37-6.39 (m, 1 H), 6.94 (part AA′, 2 H), 7.07 (part BB′, 2 H), 7.40 (ddd, J = 8.3 Hz, 6.9 Hz, 1.2 Hz, 1 H), 7.52 (ddd, J = 8.2 Hz, 6.9 Hz, 1.2 Hz, 1 H), 7.96-7.98 (m, 1 H), 8.39-8.41 (m, 1 H), 8.70 (broad s, 1 H); δ_C = 138.35, 133.86, 131.67, 130.84, 130.51, 130.14, 128.78, 127.55, 127.30, 125.95, 124.74, 124.52, 122.25, 119.57, 119.27, 102.45, 13.73; HRMS: 323.0535; calcd. for C₁₉H₁₄NS³⁵Cl: 323.0536; 4e: δ_H = 2.56 (d, J = 0.8 Hz, 3 H), 6.40-6.41 (m, 1 H), 7.39 (dd, J = 8.3 Hz, 4.3 Hz, 1 H), 7.76 (dd, J = 8.8 Hz, 0.8 Hz, 1 H), 7.85 (d, J = 8.8 Hz, 1 H), 8.30 (ddd, J = 8.3 Hz, 1.7 Hz, 0.8 Hz, 1 H), 8.81 (dd, J = 4.3 Hz, 1.7 Hz, 1 H), 8.89 (br s, 1 H); δ_C = 146.99, 145.71, 134.40, 127.38, 125.12, 123.84, 121.66, 120.95, 119.96, 116.52, 102.43, 13.80; HRMS: 182.0841; calcd. for C₁₂H₁₀N₂: 182.0844; 4f: δ_H = 2.46 (d, J = 0.8 Hz, 3 H), 4.00 (s, 3 H), 6.31-6.33 (m, 3 H), 7.32 (dd, J = 8.3 Hz, 4.3 Hz, 1 H), 8.77 (dd, J = 4.3 Hz, 1.7 Hz, 1 H), 9.75 (br s, 1 H); δ_C = 149.72, 145.62, 137.83, 134.75, 127.98, 124.17, 123.87, 120.65, 117.50, 55.88, 13.63; HRMS: 21.0946; calcd. for C₁₃H₁₂N₂O: 212.0949.

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