Download PDF
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
Further Information

Publication History

Received 26 February 2010
Publication Date:
15 April 2010 (online)

    Permissions and Reprints All articles of this category

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

  • 1a Attanasi OA. De Crescentini L. Filippone P. Mantellini F. Santeusanio S. ARKIVOC  2002,  (xi):  274 
    Google Scholar
  • 1b Attanasi OA. De Crescentini L. Favi G. Filippone P. Mantellini F. Perrulli FR. Santeusanio S. Eur. J. Org. Chem.  2009,  3109 
    Google Scholar
  • 2a Attanasi OA. Caglioti L. Org. Prep. Proced. Int.  1986,  18:  299 
    Google Scholar
  • 2b Schantl JG. In Houben-Weyl   Vol E15:  Kropf H. Schaumann E. Thieme; Stuttgart: 1990.  p.909-1100  
    Google Scholar
  • 3a Zelenin KN. Matveeva ZM. Ermolaeva LYu. Zh. Org. Khim.  1970,  6:  723 
    Google Scholar
  • 3b Zelenin KN. Bezhan IP. Matveeva ZM. Khim. Geterosikl. Soedin.  1972,  579 
    Google Scholar
  • 3c Zelenin KN. Nikitin VA. Anodina NM. Khim. Geterosikl. Soedin.  1973,  124 
    Google Scholar
  • 4a Boger DL. Tetrahedron  1983,  39:  2869 
    Google Scholar
  • 4b Gilchrist TL. Stevens JA. Parton B. J. Chem. Soc., Perkin Trans. 1  1985,  1741 
    Google Scholar
  • 4c Boger DL. Chem. Rev.  1986,  86:  781 
    Google Scholar
  • 4d Boger DL. Weinreb SM. Hetero Diels-Alder Methodology in Organic Synthesis   Academic Press; San Diego: 1987. 
    Google Scholar
  • 4e Fringuelli F. Taticchi A. Dienes in the Diels-Alder Reaction   Wiley Interscience; New York: 1990. 
    Google Scholar
  • 4f South MS. Jakuboski TL. Westmeyer MD. Dukesherer DR. J. Org. Chem.  1996,  61:  8921 
    Google Scholar
  • 4g South MS. J. Heterocycl. Chem.  1999,  36:  301 
    Google Scholar
  • 4h Attanasi OA. De Crescentini L. Filippone P. Fringuelli F. Mantellini F. Matteucci M. Piermatti O. Pizzo F. Helv. Chim. Acta  2001,  84:  513 
    Google Scholar
  • 4i Fringuelli F. Taticchi A. The Diels-Alder Reaction: Selected Practical Methods   John Wiley and Sons; New York: 2002. 
    Google Scholar
  • 5 D’Auria M. Racioppi R. Viggiani L. Zanirato P. Eur. J. Org. Chem.  2009,  932 
    CrossrefGoogle Scholar
  • 8 Frisch MJ. Trucks GW. Schlegel HB. Scuseria GE. Robb MA. Cheeseman JR. Montgomery JA. Vreven T. Kudin KN. Burant JC. Millam JM. Iyengar SS. Tomasi J. Barone V. Mennucci B. Cossi M. Scalmani G. Rega N. Petersson GA. Nakatsuji H. Hada M. Ehara M. Toyota K. Fukuda R. Hasegawa J. Ishida M. Nakajima T. Honda Y. Kitao O. Nakai H. Klene M. Li X. Knox JE. Hratchian HP. Cross JB. Adamo C. Jaramillo J. Gomperts R. Stratmann RE. Yazyev O. Austin AJ. Cammi R. Pomelli C. Ochterski JW. Ayala PY. Morokuma K. Voth GA. Salvador P. Dannenberg JJ. Zakrzewski VG. Dapprich S. Daniels AD. Strain MC. Farkas O. Malick DK. Rabuck AD. Raghavachari K. Foresman JB. Ortiz JV. Cui Q. Baboul AG. Clifford S. Cioslowski J. Stefanov BB. Liu G. Liashenko A. Piskorz P. Komaromi I. Martin RL. Fox DJ. Keith T. Al-Laham MA. Peng CY. Nanayakkara A. Challacombe M. Gill PMW. Johnson B. Chen W. Wong MW. Gonzalez C. Pople JA. Gaussian 03, Revision A.1   Gaussian Inc.; Pittsburgh: 2003. 
    Google Scholar
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.