5H-Cyclopentapyrazines from 1,2-Dialkynylimidazoles

Abstract

Acyclic C,N-dialkynylimines are a class of aza-enediynes that have been recently shown to undergo Bergman-type cyclization to unreactive 2,5-didehydropyridine intermediates, which collapse to isomeric β-acrylonitrile products. In an effort to determine the effect of incorporating the aza-enediyne functionality into heterocyclic rings on the thermal rearrangements of these systems, we have prepared a series of 1,2-dialkynylimidazoles, whose thermal rearrangement in 1,4-cyclohexadiene were studied. The major products are spiro[bicyclo[4.1.0]heptane-7,5′-[5H]cyclopentapyrazines] and 5H-cyclopentapyrazines, presumably derived from the corresponding cyclopentapyrazine carbene intermediates. The remarkable molecular rearrangements involved in this process are examined in light of a proposed aza-Bergman-retro-aza-Bergman cascade.

carbenes - aza-enediyne - Bergman reaction - rearrangements - heterocycles

References

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11

Characterization of Compound 2: mp 84-86 °C. ¹H NMR (300 MHz, CDCl₃): δ = 0.28 (s, 9 H), 6.98 (d, 1 H, J = 1.6 Hz), 7.22 (d, 1 H, J = 2 Hz) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = -0.34, 77.89, 90.32, 94.07, 125.22, 132.06 ppm. HRMS: m/z calcd for C₈H₁₂N₂SiI [MH⁺]: 290.9814; found: 290.9816.

12

Selected characterization data. Compound 3a: ¹H NMR (300 MHz, CDCl₃): δ = 3.19 (s, 1 H), 3.38 (s, 1 H), 7.02 (d, 1 H, J = 1.2 Hz), 7.14 (d, 1 H, J = 1.2 Hz) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 60.97, 70.49, 71.56, 82.28, 122.68, 129.57, 134.34 ppm. HRMS: m/z calcd for C₇H₅N₂ [MH⁺]: 117.0452; found: 117.0447.

13

Selected characterization data. Compound 4d: ¹H NMR (400 MHz, CDCl₃): δ = 0.99 (t, J = 7.2 Hz, 3 H), 1.72 (sextet, J = 7.6 Hz, 7.2 Hz, 2 H), 2.26 (dt, J = 2 Hz, 7.6 Hz, 2 H), 2.40-2.36 (m, 2 H), 2.65-2.63 (m, 2 H), 2.77-2.70 (m, 2 H), 5.80 (s, 2 H), 6.90 (t, J = 2.2 Hz, 1 H), 8.05 (d, J = 3 Hz, 1 H), 8.23 (d, J = 3 Hz, 1 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 14.13, 20.95, 21.37, 26.03, 32.28, 41.19, 124.33, 125.53, 137.13, 140.55, 155.12, 159.60, 162.08 ppm. HRMS: m/z calcd for C₁₆H₁₉N₂ [MH⁺]: 239.1548; found: 239.1550. Compound 4′d: ¹H NMR (400 MHz, CDCl₃): δ = 1.046 (t, J = 6.8 Hz, 3 H), 1.75 (sextet, J = 7.6 Hz, 6.8 Hz, 2 H), 2.08 (dt, J = 1.6 Hz, 7.6 Hz, 2 H), 2.31-2.25 (m, 4 H), 2.59-2.52 (m, 2 H), 5.89 (br s, 2 H), 6.71 (t, J = 1.6 Hz, 1 H), 8.10 (d, J = 3.2 Hz, 1 H), 8.19 (d, J = 2.8 Hz, 1 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 14.16, 20.00, 20.92, 23.86, 28.52, 39.42, 124.99, 124.16, 136.26, 139.49, 158.65, 158.89, 160.88 ppm. HRMS: m/z calcd for C₁₆H₁₉N₂ [MH⁺]: 239.1548; found: 239.1545. Compound 5c: ¹H NMR (400 MHz, CDCl₃): δ = 3.39 (d, J = 1.2 Hz, 2 H), 7.48 (s, 1 H), 7.40 (d, J = 8.4 Hz, 2 H), 7.80 (d, J = 8.4 Hz, 2 H), 8.29 (d, J = 3.0 Hz, 1 H), 8.40 (d, J = 3.0 Hz, 1 H) ppm. ¹³C NMR (100 MHz, CDCl₃): δ = 38.33, 123.89, 125.99, 126.30, 127.78, 130.91, 137.71, 139.65, 142.69, 149.84, 157.87, 158.92 ppm. HRMS: m/z calcd for C₁₃H₁₃N₂ [MH⁺]: 263.0796; found: 263.0803.

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16

All calculations were carried out with the Gaussian 98 package: Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, J. A. Jr.; Stratmann, R. E.; Burant, J. C.; Dapprich, S.; Millam, J. M.; Daniels, A. D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi, M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford, S.; Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.; Rega, N.; Salvador, P.; Dannenberg, J. J.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Cioslowski, J.; Ortiz, J. V.; Baboul, A. G.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Andres, J. L.; Gonzalez, C.; Head-Gordon, M.; Replogle, E. S.; Pople, J. A. Gaussian 98, Revision A.11.4; Gaussian, Inc.: Pittsburgh, PA, 2002.

17

We were unable to find a singlet state stationary point corresponding to the diradical 6a; calculations with this starting geometry optimized to the cumulene 7a.