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Synlett 2010(9): 1363-1366  
DOI: 10.1055/s-0029-1219834
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Unusual [4+2]-Cycloaddition Reaction between Electron-Poor 1,2-Diaza-1,3-dienes and Electron-Poor Alkenes: Useful Entry to Novel Tetrahydropyridazines

Maurizio D’Auria*a, Rocco Racioppia, Orazio A. Attanasib, Fabio Mantellinib
a Dipartimento di Chimica, Università della Basilicata, Via N. Sauro 85, 85100 Potenza, Italy
Fax: +39(0971)202223; e-Mail: maurizio.dauria@unibas.it;
b Istituto di Chimica Organica della Facoltà di Scienze e Tecnologie, Università degli Studi di Urbino ‘Carlo Bo’, Via I. Maggetti 24, 61029 Urbino, Italy
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Publikationsverlauf

Received 26 February 2010
Publikationsdatum:
15. April 2010 (online)

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Abstract

1,2-Diaza-1,3-dienes react with electron-poor alkenes to give the corresponding tetrahydropyridazines with high regio- and stereoselectivity. Both regio- and stereoselectivity can be explained considering the interaction between the LUMO of the 1,2-diaza-1,3-diene and HOMO-1 of the alkene.

Key words

1,2-diaza-1,3-dienes - electron-poor alkenes - [4+2] cycloaddition - regioselectivity - stereoselectivity - DFT calculations

    References and Notes

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6

Synthesis of Compound 3a
DD 1a (370 mg; 2 mmol) was added under vigorous stirring to a solution of methyl crotonate (2a, 2.0 g; 20 mmol) in MeCN (40 mL). The reaction was heated to reflux for 48 h, and then the solvent was evaporated under reduced pressure to afford the crude mixture, which was chromatographed on silica gel (EtOAc-PE, 1:1 to 7:3) to give pure THP 3a (370 mg, 65% yield).

7

Compound 3a: ¹H NMR (500 MHz, CDCl3): δ = 6.40-6.00 (2 H, br s), 5.00 (1 H, q, J = 6.8 Hz), 4.17 (2 H, m), 3.65 (3 H, s), 3.51 (1 H, s), 3.42 (1 H, s), 2.14 (3 H, s), 1.26 (3 H, t, J = 7.2 Hz), 1.04 (3 H, d, J = 6.8 Hz) ppm. ¹³C NMR (125 MHz, CDCl3): δ = 169.49, 167.29, 153.79, 139.07, 59.58, 50.46, 41.53, 40.98, 38.56, 22.02, 14.42, 11.61 ppm. MS: m/z (%) 285 (23), 239 (80), 226 (7), 211 (10), 197 (10), 196 (38), 184 (7), 183 (28), 181 (13), 169 (18), 168 (10), 167 (48), 155 (8), 154 (23), 153 (100), 141 (13), 139 (8), 137 (27), 128 (22), 109 (32), 96 (27), 95 (35). Anal. Calcd (%) for C12H19N3O5: C, 50.52; H, 6.71; N, 14.73. Found: C, 50.55; H, 6.68; N, 14.75.
Compound 3b: ¹H NMR (500 MHz, CDCl3): δ = 6.40-5.80 (2 H, br s), 5.01 (1 H, q, J = 6.8 Hz), 3.70 (3 H, s), 3.64 (3 H, s), 3.57 (1 H, s), 3.41 (1 H, s), 2.56 (1 H, dq, J 1 = J 2 = 7.6 Hz), 2.37 (1 H, dq, J 1 = J 2 = 7.6 Hz), 1.11 (3 H, t, J = 7.6 Hz), 1.03 (3 H, d, J = 6.8 Hz) ppm.¹³C NMR (125 MHz, CDCl3): δ = 171.92, 170.63, 156.55, 145.15, 52.98, 52.89, 44,40, 43.53, 39.55, 30.50, 17.12, 10.68 ppm. MS: m/z (%) = 285 (19), 254 (17), 253 (52), 226 (10), 211 (11), 210 (25), 183 (29), 181 (17), 168 (18), 167 (100), 151 (13), 142 (10), 128 (18), 123 (16), 113 (10), 110 (11), 109 (21), 96 (11). Anal. Calcd (%) for C11H17N3O5: C, 48.70; H, 6.32; N, 15.49. Found: C, 48.73; H, 6.36; N, 15.46.
Compound 3c: ¹H NMR (500 MHz, CDCl3): δ = 8.44 (1 H, s), 7.41 (2 H, m), 7.20 (2 H, m), 6.94 (1 H, m), 5.07 (1 H, q, J = 7.5 Hz), 3.70 (3 H, s), 3.62 (3 H, s), 3.52 (1 H, s), 3.44 (1 H, s), 2.19 (3 H, s), 1.05 (3 H, d, J = 7.5 Hz) ppm. ¹³C NMR (125 MHz, CDCl3): δ = 172.02, 170.37, 152.19, 141.57, 138.62, 129.11, 123.18, 119.34, 53.16, 53.04, 44.26, 43.67, 41.16, 24.68, 17.04 ppm. MS: m/z (%) = 348 (8), 347 (44), 316 (9), 315 (40), 197 (21), 196 (70), 170 (8), 169 (59), 167 (13), 155 (14), 154 (24), 153 (100), 138 (18), 129 (38), 109 (26), 96 (24), 95 (28), 77 (12). Anal. Calcd (%) for C17H21N3O5: C, 58.78; H, 6.09; N, 12.10. Found: C, 58.72; H, 6.12; N, 12.05.
Compound 3d: ¹H NMR (500 MHz, CDCl3): δ = 6.50-6.00 (2 H, br s), 4.71 (1 H, d, J = 1.0 Hz), 4.19 (2 H, m), 3.74 (3 H, s), 3.67 (1 H, s), 3.45 (1 H, dd, J 1 = J 2 = 1.0 Hz), 2.75 (1 H, d, J = 1.0 Hz), 2.12 (3 H, s), 1.29 (3 H, t, J = 7.0 Hz) ppm. ¹³C NMR (125 MHz, CDCl3): δ = 170.87, 168.54, 156.71, 139.75, 62.06, 52.50, 43.88, 39.26, 37.16, 23.53, 14.29 ppm. MS: m/z (%) = 271 (10), 226 (8), 225 (36), 212 (8), 183 (9), 182 (24), 170 (9), 169 (92), 167 (9), 155 (14), 154 (16), 153 (28), 141 (16), 140 (8), 139 (45), 128 (30), 123 (23), 114 (11), 97 (7), 96 (32), 95 (100), 82 (28), 68 (10), 67 (8), 59 (8), 55 (24), 54 (12), 53 (9), 44 (26). Anal. Calcd (%) for C11H17N3O5: C, 48.70; H, 6.32; N, 15.49. Found: C, 48.65; H, 6.35; N, 15.52.
Compound 3e: ¹H NMR (500 MHz, CDCl3): δ = 6.20-5.10 (2 H, br s), 4.10 (2 H, q, J = 7.0 Hz), 3.63 (3 H, s), 3.10 (1 H, dd, J 1 = 12.0 Hz, J 2 = 5.6 Hz), 2.31 (1 H, s), 1.95 (1 H, dd, J 1 = 12.0 Hz, J 2 = 5.6 Hz), 1.91 (3 H, s), 1.39 (3 H, s), 1.22 (3 H, t, J = 7.0 Hz) ppm. ¹³C NMR (125 MHz, CDCl3): δ = 173.26, 170.92, 156.40, 140.74, 61.90, 60.47, 56.82, 56.52, 40.26, 32.43, 20.36, 14.25 ppm. MS: m/z (%) = 285 (4), 242 (6), 184 (12), 183 (100), 142 (12), 109 (28), 96 (10). Anal. Calcd (%) for C12H19N3O5: C, 50.52; H, 6.71; N, 14.73. Found: C, 50.55; H, 6.68; N, 14.77.
Compound 3f: ¹H NMR (500 MHz, CDCl3): δ = 9.40 (1 H, s), 7.07 (1 H, dq, J 1 = 14.0 Hz, J 2 = 7.0 Hz), 6.20-6.00 (1 H, br s), 5.91 (1 H, dd, J 1 = J 2 = 14.0 Hz), 5.7 (1 H, br s), 5.57 (1 H, d, J = 14.0 Hz), 4.21 (2 H, q, J = 7.0 Hz), 1.94 (3 H, s), 1.89 (3 H, d, J = 7.0 Hz), 1.26 (3 H, t, J = 7.0 Hz) ppm. ¹³C NMR (125 MHz, CDCl3): δ = 176.00, 167.35, 165.29, 158.80, 147.39, 143.35, 121.55, 62.21, 18.40, 14.33, 13.00 ppm. MS: m/z (%) = 255 (29), 227 (12), 226 (100), 209 (50), 184 (10), 183 (67), 181 (10), 167 (27), 166 (30), 151 (47), 142 (20), 139 (30), 137 (26), 125 (10), 124 (20), 123 (26), 111 (32), 110 (10), 109 (23), 98 (22), 97 (13), 96 (33), 95 (57), 94 (11), 83 (24), 70 (14), 69 (72), 68 (13). Anal. Calcd (%) for C11H17N3O4: C, 51.76; H, 6.71; N, 16.46. Found: C, 51.80; H, 6.65; N, 16.42.
Compounds 3g and 3h: ¹H NMR (500 MHz, CDCl3): δ = 9.11 (s, 1 H), 7.15 (3 H, m), 7.01 (2 H, m), 6.60-6.10 (0.33 H, br s), 6.07 (0.66 H, s), 5.60-5.00 (0.66 H, br s), 4.91 (0.33 H, s), 4.05 (2 H, m), 3.82 (0.66 H, s), 3.67 (1.98 H, s), 3.64 (0.33 H, s), 3.58 (0.99 H, s), 3.38 (0.66 H, s), 3.09 (0.33 H, s), 2.08 (1.98 H, s), 2.05 (0.99 H, s), 1.13 (3 H, t, J = 7.0 Hz) ppm. ¹³C NMR (125 MHz, CDCl3): δ = 171.57, 170.36, 169.54, 168.38, 157.08, 156.58, 142.70, 141.43, 140.87, 137.23, 129.22, 128.53, 127.82, 127.72, 126.97, 126.18, 62.16, 61.57, 53.65, 53.17, 46.22, 44.07, 40.85, 38.67, 24.78, 24.20, 14.16, 13.72. MS (3g): m/z (%) = 347 (36), 302 (21), 301 (100), 226 (17), 258 (13), 243 (20), 242 (14), 231 (30), 230 (28), 229 (73), 217 (18), 216 (10), 215 (38), 202 (24), 200(29), 199 (43), 190 (21), 189 (35), 188 (13), 172 (16), 171 (70), 167 (13), 159 (13), 158 (47), 157 (13), 156 (16), 155 (17), 154 (32), 153 (26), 146 (19), 143 (10), 142 (12), 141 (17), 139 (10), 131 (38), 130 (42), 129 (12), 128 (48), 127 (10), 115 (23), 113 (11), 106 (20), 105 (19), 104 (73), 103 (26), 96 (27), 95 (36), 91 (14), 78 (10), 77 (39), 68 (12). MS (3h): m/z (%) = 347 (13), 304 (11), 288 (38), 246 (16), 245 (100), 204 (23), 199 (10), 172 (15), 171 (61), 158 (23), 131 (18), 130 (20), 103 (15), 95 (19). Anal. Calcd (%) for C17H21N3O5: C, 58.78; H, 6.09; N, 12.10. Found: C, 58.70; H, 6.15; N, 12.16.