Regioselectivity and Reactivity of Intramolecular [2+2] Cycloaddition Reactions of Acyl Ketenes: Experimental and Theoretical Studies

Abstract

The regioselectivity of the intramolecular [2+2] cycloaddition reaction of acyl ketenes formed from metastable mesoionic 1,3-oxazinium-4-olates was investigated by experimental and theoretical methods. The ring opening of the mesoionic N-allyl-2-(2-arylvinyl)-1,3-oxazinium-4-olates led to the formation of unstable acyl ketenes. ­Although there are four possible paths for an intramolecular [2+2] cyclo­addition reaction involving the two double bonds (vinyl and allyl), only the intramolecular [2+2] criss-cross cycloaddition reaction through the vinyl double bond occurred to give 3-allyl-3-azabicyclo[3.1.1]heptane-2,4,6-trione derivatives. These products were not formed when a strongly electron-withdrawing group was present on the aryl group of acrylamides or benzamides. To understand the mechanism of the reaction, density functional theory calculations at the M06-2X/6-31+G(d) level were performed. These revealed that the formation of some preliminary intermediates plays a significant role in the formation of mesoionic 1,3-oxazinium-4-olates.

Keywords

chlorocarbonylphenylketene - oxazinium olates - [2+2] cyclo­addition - acyl ketenes - density functional theory

• References and Notes

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• 17 N-Allylcinnamamide (2a) Pale-yellow crystals; yield: 0.13 mg (70%); mp 90–91 °C. IR (KBr): 3285 (NH), 3036 (C–H, sp²), 1654 (C=O), 1620, 1493 (C=C, arom) cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 8.29 (t, J = 5.6 Hz, 1 H, NH), 7.58–7.56 (m, 2 H, arom), 7.46–7.42 (m, 2 H, C₃–H, arom), 7.40–7.35 (m, 2 H, arom), 6.70 (d, ³ J _H–H = 12 Hz, 1 H, C₂–H), 5.90–5.81 (m, 1 H, C_2allyl–H), 5.18 (dd, ³ J _trans = 17.2, ² J _gem = 1.6 Hz, 1 H, C_3allyl–H), 5.10 (dd, ³ J _cis = 10.4, ² J _gem = 1.6 Hz, 1 H, C_3allyl–H), 2.03 (m, 2 H, C_allyl–H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 164.74 (C=O), 138.74 (C3), 135.20 (arom), 134.84 (C_2allyl), 129.41 (arom), 128.90 (arom), 127.47 (arom), 121.99 (C2), 115.26 (C_3allyl), 41.01 (C_allyl). Anal. Calcd for. C₁₂H₁₃NO: C, 76.98; H, 7.00; N, 7.48. Found: C, 76.93; H. 7.02; N; 7.50. 3-Allyl-1,7-diphenyl-3-azabicyclo[3.1.1]heptane-2,4,6-trione (3a) White crystals; yield: 0.29 g (88%); mp 150–152 °C. IR (KBr): 3061 (C–H, sp²), 2942 (C–H, sp³), 1795, 1744, 1698, 1499, 1459 cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 7.30 (d, ³ J _H–H = 1.6 Hz, 1 H, arom), 7.28 (d, ³ J _H–H = 1.6 Hz, 1 H, arom), 7.24–7.16 (m, 8 H, arom), 5.92–5.82 (m, 1 H, C_2allyl–H), 5.17 (dd, ³ J _cis = 10.4, ² J _gem = 1.2 C_3allyl–H) Hz, 1 H, 5.14 (dd, ³ J _trans = 17.2, ² J _gem = 1.2 Hz, 1 H, C_3allyl–H), 4.76 (s, 1 H, C₅–H), 4.67 (d, ³ J _H–H = 0.8 Hz, 1 H, C₇–H), 4.31–4.30 (m, 2 H, C_allyl–H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 189.14 (C=O), 168.90 (C=O), 167.58 (C=O), 135.47 (arom), 131.87 (arom), 130.96 (C_2allyl), 128.48 (arom), 128.23 (arom), 127.95 (arom), 127.91 (arom), 127.82 (arom), 127.75 (arom), 116.74 (C_3allyl), 84.32 (C₁), 70.72 (C₅), 45.67 (C_allyl), 42.41 (C₇). MS: m/z (%) = 331 (20.8, parent peak), 303 (19.0), 220 (89.8), 191 (55.6), 165 (19.1), 118 (100, base peak), 77 (43.8), 41 (21.9). Anal. Calcd for. C₂₁H₁₇NO₃: C, 76.12; H, 5.17; N, 4.23. Found: C, 76.17; H. 5.18; N; 4.19. 3-Allyl-7-(3-bromophenyl)-1-phenyl-3-azabicyclo[3.1.1]heptane-2,4,6-trione (3b) White crystals; yield: 0.37 g (90%); mp 139–141 °C. IR (KBr): 3061 (C–H, sp²), 1797 (C=O), 1739 (C=O), 1695 (C=O), 1596, 1480 (C=C) cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 7.42–7.41 (m, 1 H, arom), 7.38–7.35 (m, 1 H, arom), 7.32–7.30 (m, 2 H, arom), 7.28–7.20 (m, 3 H, arom), 7.18–7.12 (m, 2 H, arom), 5.91–5.82 (m, 1 H, C_2allyl–H), 5.19 (d, J _H–H = 1.2 Hz, 1 H, C_3allyl–H), 5.15 (dd, ³ J _H–H = 8.4, ² J _H–H = 1.2 Hz, 1 H, C_3allyl–H), 4.78 (s, 1 H, C₅–H), 4.76 (d, ³ J _H–H = 0.8 Hz, 1 H, C₇–H), 4.30–4.29 (m, 2 H, C_allyl–H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 188.82 (C=O), 168.62 (C=O), 167.32 (C=O), 138.01 (arom), 131.79 (arom), 131.08 (C_2allyl), 130.84 (arom), 130.70 (arom), 130.55 (arom), 128.18 (arom), 128.02 (arom), 127.85 (arom), 126.60 (arom), 121.58 (arom), 116.76 (C_3allyl), 84.23 (C₁), 70.46 (C₅), 44.89 (C_allyl), 42.43 (C₇). MS: m/z (%) = 411 (14.1, M + 2), 409 (14.3, parent peak), 383 (15.3), 298 (41.6), 196 (100), 102 (69.6), 41 (28.7). Anal. Calcd for. C₂₁H₁₆BrNO₃: C, 61.48; H, 3.93; N, 3.41. Found: C, 61.42; H. 3.95; N; 3.37. 3-Allyl-7-(4-chlorophenyl)-1-phenyl-3-azabicyclo[3.1.1]heptane-2,4,6-trione (3c) White crystals; yield: 0.32 g (89%); mp 145–146 °C. IR (KBr): 3064 (C–H, sp²), 1790 (C=O), 1744 (C=O), 1687 (C=O), 1496, 1448 (C=C) cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 7.49–7.41 (m, 3 H, arom), 7.31–7.18 (m, 6 H, arom), 5.91–5.81 (m, 1 H, C_2allyl–H), 5.17 (dd, ³ J _trans = 12.8, ² J _gem = 1.6 Hz, 1 H, C_3allyl–H), 5.09 (dd, ³ J _cis = 10.4, ² J _H–H = 1.6 Hz, 1 H, C_3allyl–H), 4.79 (s, 1 H, C₅–H), 4.71 (d, ³ J _H–H = 0.8 Hz, 1 H, C₇–H), 4.30–4.29 (m, 2 H, C_allyl–H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 188.91 (C=O), 168.70 (C=O), 167.40 (C=O), 137.40 (arom), 133.82 (arom), 131.82 (C_2allyl), 129.76 (arom), 129.18 (arom), 128.93 (arom), 128.48 (arom), 127.86 (arom), 122.80 (arom), 116.78 (C_3allyl), 84.27 (C₁), 70.59 (C₅), 44.91 (C_allyl), 42.44 (C₇). MS: m/z (%) = 367 (4.1, M + 2), 365 (11.6, parent peak), 339 (17.6), 254 (53.9), 219 (30.2), 191 (54.9), 152 (100, base peak), 102 (28.7), 41 (18.7). Anal. Calcd for. C₂₁H₁₆ClNO₃: C, 68.95; H, 4.41; N, 3.83. Found: C, 68.98; H. 4.38; N; 3.80. 3-Allyl-1-phenyl-7-(4-tolyl)-3-azabicyclo[3.1.1]heptane-2,4,6-trione (3d) White crystals; yield: 0.25 g (75%); mp 140–142 °C. IR (KBr): 3061 (C–H, sp²), 1795 (C=O), 1742 (C=O), 1697 (C=O), 1499, 1459 (C=C) cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 7.33–7.20 (m, 7 H, arom), 7.07–6.99 (m, 2 H, arom), 5.91–5.81 (m, 1 H, C_2allyl–H), 5.16 (dd, ³ J _cis = 12.0, ² J _gem = 1.2 Hz, 1 H, C_3allyl–H), 5.13 (dd, ³ J _trans = 16.8, ² J _gem = 1.2 Hz, 1 H, C_3allyl–H), 4.71 (s, 1 H, C₅–H), 4.60 (s, 1 H, C₇–H), 4.29–4.28 (m, 2 H, C_allyl–H), 1.92 (s, 3 H, CH₃). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 188.17 (C=O), 169.52 (C=O), 167.62 (C=O), 134.98 (arom), 130.98 (C_2allyl), 129.32 (arom), 129.26 (arom), 128.42 (arom), 128.26 (arom), 128.19 (arom), 127.80 (arom), 126.53 (arom), 119.45 (C_3allyl), 84.39 (C₁), 68.05 (C₅), 45.42 (C_allyl), 43.58 (C₇), 22.06 (CH₃). MS: m/z (%) = 345 (1.2, parent peak), 319 (23.0), 234 (9.3), 194 (23.5), 145 (79.4), 118 (51.5), 91 (100, base peak), 43 (43.3). Anal. Calcd for. C₂₂H₁₉NO₃: C, 76.50; H, 5.54; N, 4.06. Found: C, 76.56; H. 5.51; N; 4.10. 3-Allyl-2-(4-methoxyphenyl)-6-oxo-5-phenyl-6H-1,3-oxazin-3-ium-4-olate (8a) Yellow crystals; yield: 0.48 g (72%); mp 132–134 °C. IR (KBr): 3064 (C–H, sp²), 1682 (C=O), 1604, 1510, 1497 (C=C) cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 17.87 (d, ³ J _H–H = 8 Hz, 1 H, arom), 7.61 (d, ³ J _H–H = 8 Hz, 1 H, arom), 7.29–7.18 (m, 5 H, arom), 7.04–6.99 (m, 2 H, arom), 5.93–5.83 (m, 1 H, C_2allyl–H), 5.18–5.05 (m, 2 H, C_3allyl–H), 3.87–3.82 (m, 5 H, C_allyl–H, CH₃O). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 174.3 (C₆), 170.5 (C₂), 163.2 (C₄), 157.3 (arom), 134.1 (C_2allyl), 131.9 (arom), 131.5 (arom), 130.0 (arom), 128.8 (arom), 127.8 (arom), 127.3 (arom), 117.4 (arom), 114.6 (C_3allyl), 86.3 (C₅), 56.5 (CH₃O), 43.4 (C_allyl). MS: m/z (%) = 335 (24.7, parent peak), 293 (9.9), 174 (6.9), 135 (100, base peak), 107 (31.7), 77 (56.8), 41 (17.7). Anal. Calcd for. C₂₀H₁₇NO₄: C, 71.63; H, 5.11; N, 4.18. Found: C, 71.60; H. 5.15; N; 4.14. 7-(4-Chlorophenyl)-1,3-diphenyl-3-azabicyclo[3.1.1]heptane-2,4,6-trione (10a) White crystals; yield: 0.32 g (80%); mp 228–230 °C. IR (KBr): 3062 (C–H, sp²), 1796 (C=O), 1750 (C=O), 1698 (C=O), 1598, 1495 (C=C) cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 17.38–7.30 (m, 7 H, arom), 7.29–7.20 (m, 7 H, arom), 5.17 (s, 1 H, C₅–H), 4.80 (d,³ J _H–H = 1.2 Hz Hz, 1 H, C₇–H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 188.5 (C=O), 169.3 (C=O), 168.0 (C=O), 135.0 (arom), 134.4 (arom), 133.2 (arom), 131.1 (arom), 130.3 (arom), 129.4 (arom), 129.3 (arom), 129.1 (arom), 129.0 (arom), 128.8 (arom), 128.5 (arom), 128.3 (arom), 84.9 (C₁), 71.4 (C₅), 45.2 (C₇). MS: m/z (%) = 403 (2.9, M + 2), 401 (7.8, parent peak), 373 (9.0), 241 (20.6), 192 (5.9), 165 (100, base peak), 137 (24.1), 102 (21.6), 77 (11.1). Anal. Calcd for. C₂₄H₁₆ClNO₃: C, 71.73; H, 4.01; N, 3.49. Found: C, 71.75; H. 4.06; N; 3.44. 7-(2,4-Dichlorophenyl)-1,3-diphenyl-3-azabicyclo[3.1.1]heptane-2,4,6-trione (10b) White crystals; yield: 0.37 g (85%); mp 215–217 °C. IR (KBr): 1796 (C=O), 1750 (C=O), 1698 (C=O), 1599, 1496 (C=C) cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 17.38–7.32 (m, 6 H, arom), 7.30–7.22 (m, 7 H, arom), 5.17 (s, 1 H, C₅–H), 4.80 (d, ² J _H–H = 0.8 Hz, 1 H, C₇–H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 188.5 (C=O), 169.3 (C=O), 168.0 (C=O), 135.0 (arom), 134.4 (arom), 133.2 (arom), 131.3 (arom), 130.3 (arom), 129.5 (arom), 129.4 (arom), 129.3 (arom), 129.1 (arom), 129.0 (arom), 128.8 (arom), 128.6 (arom), 128.5 (arom), 128.3 (arom), 85.0 (C₁), 71.4 (C₅), 45.2 (C₇). MS: m/z (%) = 437 (0.07, M + 2), 435 (0.08, parent peak), 373 (9.8), 254 (18.6), 213 (24.8), 165 (100, base peak), 102 (23.2), 63 (8.0). Anal. Calcd for. C₂₄H₁₅Cl₂NO₃: C, 66.07; H, 3.47; N, 3.21. Found: C, 66.04; H. 3.50; N; 3.23.