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DOI: 10.1055/s-0029-1219834
Unusual [4+2]-Cycloaddition Reaction between Electron-Poor 1,2-Diaza-1,3-dienes and Electron-Poor Alkenes: Useful Entry to Novel Tetrahydropyridazines
Publication History
Publication Date:
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
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References and Notes
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).
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.