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Synlett 2007(7): 1031-1036  
DOI: 10.1055/s-2007-973891
LETTER
© Georg Thieme Verlag Stuttgart · New York

Sequential Alkylation/Heterocyclization of β-(2-Aminophenyl)-α,β-ynones Promoted by Electrogenerated Carbanions: A New Approach to ­Functionalized 4-Alkylquinolines

Antonio Arcadi*a, Gabriele Bianchia, Achille Inesib, Fabio Marinellia, Leucio Rossi*a
a Dipartimento di Chimica, Ingegneria Chimica e Materiali, Università degli Studi dell’Aquila, via Vetoio - Coppito due, 67010 L’Aquila, Italy
Fax: +(39)0862433753; e-Mail: arcadi@univaq.it; e-Mail: rossil@ing.univaq.it;
b Dipartimento di Ingegneria Chimica, Materie Prime, Metallurgia, Università ‘La Sapienza’, via del Castro Laurenziano 7, 00137 Roma, Italy
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Publication History

Received 30 January 2007
Publication Date:
13 April 2007 (online)

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Abstract

Electrolysis in a divided cell (nitroalkanes or methanol, in the absence of solvent and supporting electrolyte, as catholite) gave functionalized 4-alkylquinolines in moderate to high yields through a sequential alkylative heterocyclization of β-(2-amino­phenyl)-α,β-ynones. The sequential alkylative heterocyclization process can be extended to the reaction of β-(2-aminophenyl)-α,β-ynones with 1,3-dicarbonyls by galvanostatic electrolysis of these latter derivatives in a tetraethylammonium tetrafluoroborate-N,N-dimethylformamide solution.

Key words

quinolines - alkynones - electrosynthesis - electrogenerated carbanions - alkylative cyclization

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β-(2-aminophenyl)-α,β-ynones 2a-d were prepared according to ref. 15c. General procedure for electrochemically promoted sequential alkylative cyclization reaction of nitroalkane 1a-c with β-(2-aminophenyl)-α,β-ynones 2: Pure nitroalkane, (2.0 mL) and TEATFB-DMF solution (0.1 M, 3.0 mL) were added to the cathodic and anodic compartment of the divided cell, respectively. The cell was equipped with a Pt mesh cathode (1.0 cm2) and a Pt spiral anode. The electrolysis was carried out under galvanostatic control (J = 30 mAcm-2, Q = 1.2 Fmol-1 referred to compound 2) at 0 °C. At the end of the electrolysis, the α,β-ynones 2 (0.2 mmol) were added to the cathode compartment and the reaction held at r.t. for the time reported in Table [1] . Once the TLC analysis showed the disappearance of 2, the excess of starting nitroalkane 1a-c was removed under vacuum and the residue purified by flash column chromatography to afford pure product 3a-j.
3b: pale yellow oil; 1H NMR (200 MHz, CDCl3): δ = 1.06 (t, J = 7.3 Hz, 3 H), 2.12-2.45 (m, 1 H), 2.34 (s, 6 H), 2.50-2.75 (m, 1 H), 6.22 (dd, J = 9.1, 5.6 Hz, 1 H), 7.05-7.15 (m, 2 H), 7.38 (d, J = 8.3 Hz, 1 H), 7.55-7.85 (m, 3 H), 8.06 (d, J = 8.1 Hz, 1 H), 8.21 (d, J = 7.9 Hz, 1 H); 13C NMR (50.3 MHz, CDCl3): δ = 10.9, 20.3, 21.2, 27.2, 87.3, 120.3, 121.8, 124.3, 125.4, 126.9, 127.6, 129.8, 130.0, 130.7, 131.8, 135.9, 138.9, 139.2, 148.4, 160.0; MS (EI): m/z (%) = 321 (13) [M + H]+, 275 (100).
3c: white solid; mp 84-86 °C; 1H NMR (200 MHz, CDCl3): δ = 1.04 (t, J = 7.3 Hz, 3 H), 2.10-2.35 (m, 1 H), 2.50-2.80 (m, 1 H), 3.79 (s, 3 H), 6.13-6.17 (m, 1 H), 6.96 (d, J = 8.8 Hz, 2 H, part of AA′BB′ system), 7.54 (t, J = 7.1 Hz, 1 H), 7.67 (t, J = 7.2 Hz, 1 H), 7.89 (s, 1 H), 8.05 (d, J = 8.8 Hz, 2 H, part of AA′BB′ system), 7.80-8.25 (m, 2 H); 13C NMR (50.3 MHz, CDCl3): δ = 10.9, 27.3, 55.4, 87.5, 114.4, 116.2, 121.8, 124.4, 125.0, 127.1, 129.0, 130.0, 130.6, 140.0, 148.6, 156.7, 161.3; MS (EI): m/z (%) = 322 (26) [M]+, 276 (100).
3d: pale brown solid; mp 110-112 °C; 1H NMR (200 MHz, CDCl3): δ = 1.05 (t, J = 7.3 Hz, 3 H), 2.12-2.32 (m, 1 H), 2.46-2.75 (m, 1 H), 3.81 (s, 3 H), 5.97 (dd, J = 8.8 Hz, 1 H), 6.93-7.05 (m, 2 H), 7.08-7.20 (m, 1 H), 7.32-7.47 (m, 2 H), 7.87 (dd, J = 7.6, 1.6 Hz, 1 H), 8.19 (s, 1 H); MS (EI): m/z (%) = 359 (25) [M + H]+, 312 (100).
3e: white solid; mp 127-129 °C; 1H NMR (200 MHz, CDCl3): δ = 2.32 (s, 3 H), 2.35 (s, 3 H), 5.90 (s, 2 H), 7.06 (s, 1 H), 7.09 (s, 1 H), 7.37 (d, J = 8.3 Hz, 1 H), 7.57 (s, 1 H), 7.60-7.75 (m, 1 H), 7.70-7.85 (m, 1 H), 7.96 (d, J = 8.3 Hz, 1 H), 8.15-8.35 (m, 1 H); 13C NMR (50.3 MHz, CDCl3): δ = 20.4, 21.2, 76.4, 122.4, 124.7, 125.1, 127.0, 128.0, 129.9, 130.2, 130.5, 131.9, 133.3, 136.1, 139.2, 159.4.
3f: white solid; mp 93-95 °C; 1H NMR (200 MHz, CDCl3): δ = 3.82 (s, 3 H), 5.90 (s, 2 H), 6.99 (d, J = 8.7 Hz, 2 H, part of AA′BB′), 7.50-7.65 (m, 1 H), 7.65-7.80 (m, 1 H), 7.83 (s, 1 H), 7.85-8.00 (m, 1 H), 8.08 (d, J = 8.7 Hz, 2 H, part of AA′BB′), 8.15-8.30 (m, 1 H).
3g: white solid; mp 53-55 °C; 1H NMR (200 MHz, CDCl3): δ = 2.09 (s, 6 H), 2.31 (s, 3 H), 2.35 (s, 3 H), 7.00-7.15 (m, 2 H), 7.30-7.75 (m, 5 H), 8.17 (d, J = 8.3 Hz, 1 H); 13C NMR (50.3 MHz, CDCl3): δ = 20.3, 21.2, 28.2, 89.4, 119.7, 122.7, 123.4, 126.9, 127.2, 129.4, 129.7, 131.2, 131.9, 136.0, 136.9, 138.9, 144.6, 148.7, 159.7; MS (EI): m/z (%) = 321 (6) [M + H]+, 274 (100).
3h: white solid; mp 107-109 °C; 1H NMR (200 MHz, CDCl3): δ = 2.12 (s, 6 H), 3.79 (s, 3 H), 6.96 (d, J = 8.8 Hz, 2 H, part of AA′BB′ system), 7.30-7.45 (m, 1 H), 7.45-7.70 (m, 2 H), 7.79 (s, 1 H), 8.04 (d, J = 8.8 Hz, 2 H, part of AA′BB′ system), 8.10-8.20 (m, 1 H); 13C NMR (50.3 MHz, CDCl3): δ = 28.1, 55.4, 89.6, 114.4, 115.9, 122.7, 123.5, 126.7, 128.9, 129.4, 131.1, 131.6, 145.1, 149.1, 156.4, 161.2; MS (EI): m/z (%) = 322 (5) [M]+, 276 (100).
3i: pale brown solid; mp 82-84 °C; 1H NMR (200 MHz, CDCl3): δ = 2.10 (s, 6 H), 3.83 (s, 3 H), 6.80-7.25 (m, 4 H), 7.30-7.50 (m, 1 H), 7.89 (dd, J = 7.6, 1.7 Hz, 1 H), 8.13 (s, 1 H); MS (EI): m/z (%) = 359 (10) [M + H]+, 312 (100).
3j: white solid; mp 196-198 °C; 1H NMR (200 MHz, CDCl3): δ = 2.20 (s, 6 H), 7.44-7.68 (m, 5 H), 7.66-7.86 (m, 3 H), 7.88-8.03 (m, 2 H), 8.05-8.15 (m, 1 H), 8.36 (d, J = 8.5 Hz, 1 H); 13C NMR (50.3 MHz, CDCl3): δ = 28.3, 89.5, 120.6, 122.8, 125.3, 125.4, 126.2, 127.0, 127.6, 128.1, 128.6, 129.7, 129.8, 130.3, 130.8, 131.3, 134.1, 137.2, 147.4, 158.9; MS (EI): m/z (%) = 341 (13) [M - H]+, 294 (100).

24

General procedure for electrochemically promoted reaction of dicarbonyl compound 1e-f to β-(2-aminophenyl)-α,β-ynones 2: A solution of dicarbonyl compound 1 (0.20 mmol) in TEATFB-DMF (0.1 M, 2 mL) and a solution of TEATFB-DMF (0.1 M, 3.0 mL) were added to the cathodic and anodic compartment of the divided cell, respectively. The cell was equipped with a Pt mesh cathode (1.0 cm2) and a Pt spiral anode. The electrolysis was carried-out under galvanostatic control (J = 30 mAcm-2, Q = 1.2 Fmol-1 referred to 2) at 0 °C. At the end of electrolysis the α,β-ynones 2 (0.2 mmol) were added to the cathode compartment and the reaction held at r.t. for the time reported in Table [1] . The mixture was then poured into NH4Cl sat. soln (50 mL) and extracted with Et2O (× 2). The organic layer, dried over Na2SO4, was evaporated in vacuo and the crude purified by flash column chromatography using hexane-Et2O mixtures to afford pure product 3.
3l: white solid; mp 180-182 °C; 1H NMR (200 MHz, CDCl3): δ = 3.73 (s, 6 H), 3.80 (s, 3 H), 5.40 (s, 1 H), 6.97 (d, J = 8.8 Hz, 2 H, part of AA′BB′ system), 7.40-7.60 (m, 1 H), 7.66 (t, J = 7.3 Hz, 1 H), 7.80-7.95 (m, 2 H), 8.07 (d, J = 8.8 Hz, 2 H, part of AA′BB′ system), 8.20 (d, J = 8.6 Hz, 1 H); 13C NMR (50.3 MHz, CDCl3): δ = 53.2, 53.4, 55.4, 114.3, 119.3, 122.4, 125.3, 126.7, 129.2, 129.8, 130.3, 131.2, 138.9, 148.4, 156.5, 161.2, 167.7; MS (EI): m/z (%) = 307 (100), 292 (35).
3m: white solid; mp 120-122 °C; 1H NMR (200 MHz, CDCl3): δ = 3.68 (s, 3 H), 3.74 (s, 3 H), 3.82 (s, 3 H), 5.20 (s, 1 H), 6.85-7.55 (m, 5 H), 7.87 (dd, J = 7.6, 1.5 Hz, 1 H), 8.10 (s, 1 H); MS (EI): m/z (%) = 251 (100), 208 (44).
3n: pale yellow oil; 1H NMR (200 MHz, CDCl3): δ = 1.00-1.35 (m, 3 H); 1.85-2.25 (m, 4 H), 2.35-2.55 (m, 2 H), 3.95-4.30 (m, 2 H), 7.20-8.05 (m, 11 H), 8.30 (d, J = 8.5 Hz, 1 H); MS (EI): m/z (%) = 409 (100) [M]+, 336 (26).