H-Bonding Organocatalysed Friedel-Crafts Alkylation of Aromatic and Heteroaromatic Systems with Nitroolefins

Abstract

Catalytic amounts (10 mol%) of bis-arylureas and -thioureas promote the Friedel-Crafts alkylation with nitroolefins of aromatic and heteroaromatic N-containing derivatives. A sizeable improvement of the yields is noticed on running the reactions in the absence of solvent. When applied to indoles this protocol provides in good to excellent yields and with high selectivity the corresponding Michael adducts. Alkylation at position 2 of the 3-methylindole can be achieved combining solvent-free reaction conditions with microwave (MW) irradiation.

organocatalysis - nitroolefins - Friedel-Crafts alkyl­ation - indoles

References

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General Experimental Procedure. In a Schlenk tube, a mixture of nitroolefin (a or b, 0.10 mmol), nitrogen-containing aromatic or heteroaromatic compound (1-6, 13-15, 0.15 mmol) and catalyst (I and II, 0.01 mmol) in toluene (1 mL) or without solvent, was vigorously stirred at ambient temperature for the appropriate time (Table [1] or Table [2] ). After completion of the reaction as indicated by ¹H NMR, the reaction mixture was diluted with H₂O and extracted with Et₂O. The organic phases were combined, dried over Na₂SO₄ and concentrated under reduced pressure, and the crude mixture was purified by column chromatography. All the new compounds gave satisfactory analytical and spectral data. Typical data for representative compounds:
Analytical data of compound 10a: IR (CCl₄): 3047, 2893, 1614, 1552, 1376, 1277, 895 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.05 (t, ³ J = 7.1 Hz, 6 H, 2 × CH ₃CH₂), 3.24 (c, ³ J = 7.2 Hz, 4 H, 2 × CH₃CH ₂), 4.71 (dd, ³ J = 8.8 Hz, ³ J = 7.5 Hz, 1 H, NO₂CH₂CH), 4.78-4.93 (m, 2 H, NO₂CH₂), 6.53 (d, ³ J = 8.7 Hz, 2 H, Ph), 6.97 (d, ³ J = 8.7 Hz, 2 H, Ph), 7.08-7.40 (m, 5 H, Ph). ¹³C NMR (400 MHz, CDCl₃): δ = 12.48 (2 × CH₃CH₂), 44.25 (NO₂CH₂ CH), 48.21 (CH₂NCH₂), 79.66 (NO₂CH₂), 111.85 (C^Ph), 125.40 (C_q ^Ph), 127.26, 127.50, 127.57, 140.03, 128.55, 128.86, (5 × C^Ph) 139.97, 147.01 (2 × C_q ^Ph). MS (70 eV): m/z (%) = 298 [M⁺], 284 (17), 283 (86), 252 (50), 238 (100), 237 (19), 236 (56), 208 (28). HRMS: m/z calcd for C₁₈H₂₂N₂O₂: 298.1681; found: 298.1684.
Analytical data of compound 18b: IR (CCl₄): 3061, 2860, 1555, 1468, 1426, 1377 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.83 (t, J = 7.1 Hz, 3 H, CH₂CH ₃), 1.12-1.36 (m, 6 H, 3 × CH₂), 1.68-1.92 (m, 2 H, NO₂CH₂CHCH ₂), 3.76 (s, 3 H, NCH₃), 3.70-3.81 (m, 1 H, NO₂CH₂CH), 4.61 (dd, ² J = 11.9 Hz, ³ J = 7.8 Hz, 1 H, NO₂CHH), 4.66 (dd, ² J = 11.9 Hz, ³ J = 7.4 Hz, 1 H, NO₂CHH), 6.89 (s, 1 H, CH₃NCH), 7.13 (t, ³ J = 7.8 Hz, 1 H, Ph), 7.25 (t, ³ J = 7.8 Hz, 1 H, Ph), 7.31 (d, ³ J = 8.2 Hz, 1 H, Ph), 7.61 (d, ³ J = 8.2 Hz, 1 H, Ph). ¹³C NMR (400 MHz, CDCl₃): δ = 13.99 (CH₂ CH₃), 22.43, 26.88, 31.61, 32.49 (4 × CH₂), 32.77 (NCH₃), 36.29 (NO₂CH₂ CH), 80.72 (NO₂CH₂), 109.56 (C^Ph), 112.54 (C_q ^Ph), 118.83, 119.20, 121.92 (3 × C^Ph), 126.55 (CH₃NCHC), 126.64, 137.23 (2 × C_q ^Ph). MS (70 eV): m/z (%) = 274 [M⁺], 228 (17), 214 (42), 171 (34), 158 (21), 157 (100), 156 (16). HRMS: m/z calcd for C₁₆H₂₂N₂O₂: 274.1681; found: 274.1687.

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