Download PDF
Synlett 2004(13): 2374-2378  
DOI: 10.1055/s-2004-832844
LETTER
© Georg Thieme Verlag Stuttgart · New York

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

Gabriella Dessolea, Raquel P. Herrera*b, Alfredo Ricci*a
a Dipartimento di Chimica Organica ‘A. Mangini’, Facoltà di Chimica Industriale, Via Risorgimento N°4, 40136-Bologna, Italy
Fax: +39(051)2093654; e-Mail: ricci@ms.fci.unibo.it;
b Universidad de Alicante, Dpto. Química Orgánica, Apdo.99, 03080-Alicante, Spain
Further Information

Publication History

Received 30 July 2004
Publication Date:
24 September 2004 (online)

    Permissions and Reprints All articles of this category

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.

Key words

organocatalysis - nitroolefins - Friedel-Crafts alkyl­ation - indoles

20

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 (CPh), 125.40 (Cq Ph), 127.26, 127.50, 127.57, 140.03, 128.55, 128.86, (5 × CPh) 139.97, 147.01 (2 × Cq 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 (CPh), 112.54 (Cq Ph), 118.83, 119.20, 121.92 (3 × CPh), 126.55 (CH3NCHC), 126.64, 137.23 (2 × Cq 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.