Mechanisms for formation of diazocinones, pyridazines, and pyrazolines from tetrazines - Oxyanion-accelerated pericyclic cascades?

Journal of Organic Chemistry

Volumn 74, Issue 13, 2009, Pages 4804-4811

  Lodewyk, Michael W ^a   Kurth, Mark J ^a   Tantillo, Dean J ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CASCADE REACTIONS; CHEMICAL EQUATIONS; COMPUTATIONAL APPROACH; CYCLOREVERSION; ELECTROCYCLIC RINGS; ENOLATES; OXYANION; PYRAZOLINE; PYRAZOLINES; PYRIDAZINE; REACTION STEPS; RING OPENING; SIGMATROPIC SHIFTS; TETRAZINES; THEORETICAL PREDICTION;

CHEMICAL REACTIONS; PYRIDINE;

POSITIVE IONS;

ANION; AZOCINE DERIVATIVE; DIAZOCINONE DERIVATIVE; PYRAZOLINE DERIVATIVE; PYRIDAZINE DERIVATIVE; TETRAZINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL STRUCTURE; ELECTRON; KINETICS; REACTION ANALYSIS; RING OPENING; STEREOCHEMISTRY; SYNTHESIS; THERMODYNAMICS;

ANIONS; AZA COMPOUNDS; CYCLIZATION; MODELS, MOLECULAR; PYRAZOLES; PYRIDAZINES; STEREOISOMERISM;

EID: 67649604268     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo900565y     Document Type: Article

References (62)

1. For reviews on the reactivity and applications of various tetrazines, see (a) Saracoglu, N. Tetrahedron 2007, 63, 4199-4236.
2. (b) Boger, D. L. Chem. Rev. 1986, 86, 781-793.
3. See for example: (a) Cioslowski, J.; Sauer, J.; Hetzenegger, J.; Karcher, T.; Hierstetter, T. J. Am. Chem. Soc. 1993, 115, 1353-1359.
4. (b) Sauer, J.; Heldmann, D. K.; Hetzenegger, J.; Krauthan, J.; Sichert, H.; Schuster, J. Eur. J. Org. Chem. 1998, 2885-2896.
5. (c) Sadasivam, D. V.; Prasad, E.; Flowers, R. A., II.; Birney, D. M. J. Phys. Chem. A 2006, 110, 1288-1294.
6. (d) Hamasaki, A.; Ducray, R.; Boger, D. L. J. Org. Chem. 2006, 71, 185-193.
7. (e) Hayden, A. E.; Houk, K. N. J. Am. Chem. Soc. 2009, 131, 4084-4089.
8. (f) Domingo, L. R.; Picher, M. T.; Sáez, J. A. J. Org. Chem. 2009, 74, 2726-2735.
9. Haddadin, M. J.; Firsan, S. J.; Nader, B. S. J. Org. Chem. 1979, 44, 629-630.
10. Haddadin, M. J.; Agha, B. J.; Salka, M. S. Tetrahedron Lett. 1984, 25, 2577-2580.
11. Robins, L. I.; Carpenter, R. D.; Fettinger, J. C.; Haddadin, M. J.; Tinti, D. S.; Kurth, M. J. J. Org. Chem. 2006, 71, 2480-2485.
12. 2 A related reaction is discussed in Camps, P.; Domingo, L. R.; Formosa, X.; Galdeano, C.; González, D.; Muñoz-Torrero, D.; Segalés, S.; Font-Bardia, M.; Solans, X. J. Org. Chem. 2006, 71, 3464-3471.
13. For reviews and leading references which discuss other oxyanion-accelerated pericyclic processes, see (a) Paquette, L. A.; Liu, Z.; Ramsey, C.; Gallucci, J. C. J. Org. Chem. 2005, 70, 8154-8161.
14. (b) Kim, S.-H.; Cho, S. Y.; Cha, J. K. Tetrahedron 2001, 42, 8769-8772.
15. (c) Wilson, S. R. In Organic Reactions; Paquette, L. A., Ed.; John Wiley & Sons, Inc.: New York, 1993: Vol.43, pp 93.
16. (d) Bronson, J. J.; Danheiser, R. L. In Comprehensive Organic Synthesis; Trost, B. M.; Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol.5, pp 999-1035.
17. (e) Zoeckler, M. T.; Carpenter, B. K. J. Am. Chem. Soc. 1981, 103, 7661-7663.
18. (f) Paquette, L. A. Tetrahedron 1997, 53, 13971-14020.
19. (g) Bunnage, M. E.; Nicolaou, K. C. Chem. - Eur. J. 1997, 3, 187-192.
20. Frisch, M. J. Gaussian03, revision D.01; Gaussian, Inc.: Pittsburgh, PA, 2003 (full reference in Supporting Information).
21. (a) Becke, A. D. J. Chem. Phys. 1993, 98, 5648-5652.
22. (b) Becke, A. D. J. Chem. Phys. 1993, 98, 1372-1377.
23. (c) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1988, 37, 785-789.
24. (d) Stephens, P. J.; Devlin, F. J.; Chabalowski, C. F.; Frisch, M. J. J. Phys. Chem. 1994, 98, 11623-11627.
25. (e) The value of diffuse functions in density functional based calculations was recently discussed in Lynch, B. J.; Zhao, Y.; Truhlar, D. G. J. Phys. Chem. A 2003, 107, 1384-1388.
26. For recent papers involving computations on enolate structures with B3LYP methods, see (a) Pratt, L. M.; Nguyen, S. C.; Thanh, B. T. J. Org. Chem. 2008, 73, 6086-6091.
27. (b) Domingo, L. R.; Arnó, M.; Merino, P.; Tejero, T. Eur. J. Org. Chem. 2006, 3464-3472.
28. (c) Zhang, X.; Houk, K. N. J. Org. Chem. 2005, 70, 9712-9716.
29. (d) Pratt, L. M.; Nguyen, N. V.; Ramachandran, B. J. Org. Chem. 2005, 70, 4279-4283.
30. (a) Gonzalez, C.; Schlegel, H. B. J. Phys. Chem. 1990, 94, 5523-5527.
31. (b) Fukui, K. Acc. Chem. Res. 1981, 14, 363-368.
32. (c) IRC plots are available in the Supporting Information.
33. With the inclusion of a potassium counterion on smaller model systems, energies for the transition-state structures and products were raised relative to the reactants; however, these numbers are not highly reliable due to the tendency of this counterion to interact with various electron-rich atoms in the structures and the presence of several conformers of these systems.
34. (a) Barone, V.; Cossi, M. J. Phys. Chem. A 1998, 102, 1995-2001.
35. (b) Barone, V.; Cossi, M.; Tomasi, J. J. Comput. Chem. 1998, 19, 404-417.
36. (c) Takano, Y.; Houk, K. N. J. Chem. Theory Comput. 2005, 1, 70-77.
37. For leading references, see (a) Schleyer, P. v. R.; Maerker, C.; Dransfeld, A.; Jiao, H.; Hommes, N. J. R. v. E. J. Am. Chem. Soc. 1996, 118, 6317-6318.
38. (b) Chen, Z.; Wannere, C. S.; Corminboeuf, C.; Puchta, R.; Schleyer, P. v. R. Chem. Rev. 2005, 105, 3842-3888.
39. Müller, N.; Falk, A.; Gsaller, G. Ball & Stick version 4.0a12, molecular graphics application for MacOS computers; Johannes Kepler University: Linz, 2004.
40. (a) Woodward, R. B.; Hoffmann, R. The Conservation of Orbital Symmetry; Verlag Chemie: Weinheim, Germany, 1970.
41. (b) Hoffmann, R.; Woodward, R. B. Acc. Chem. Res. 1968, 1, 17-22, and references therein.
42. (c) Woodward, R. B.; Hoffmann, R. Angew. Chem., Int. Ed. Engl. 1969, 8, 781-853.
43. Efforts here included constrained calculations and a relaxed potential energy surface scan (see Supporting Information) where the C3-C4 distance was gradually decreased. This scan revealed no energetic well down to 1.4 Å.
44. Tantillo, D. J. J. Phys. Org. Chem. 2008, 21, 561-570.
45. Although not exactly the same, this situation bears resemblance to so-called "bis-pericyclic" reactions, where two cycloadditions are merged into a single process. For leading references and a discussion of these and other hybrid pericyclic reactions, see Nouri, D. H.; Tantillo, D. J. J. Org. Chem. 2006, 71, 3686-3695.
46. One would expect that the vibrations corresponding to the imaginary frequencies of the transition structures leading to the disrotatory and conrotatory products would display these same motions upon animation. However, the situation appears to be complicated by the strongly interacting oxygen atom. While the hydrogen atom on C7 clearly rotates outwards in TS4 → 6, and clearly rotates inwards in TS4 → 7, the movement of the oxygen atom appears to correspond primarily to planarization of the carbon center in both animations. That is, the oxygen atom does not appear to rotate in a clear sense in either case. See Supporting Information for additional discussion and details including animated movies of imaginary frequencies. For a related ring-opening process, see Polo, V.; Domingo, L. R.; Andrés, J. J. Org. Chem. 2006, 71, 754-762.
47. Benzene at the same level of theory has a NICS(0) value of -7.7, and the parent six-electron electrocyclization (hexatriene → cyclohexadiene) has a NICS(0) value of -13.4 ppm.
48. Grob, C. A. Angew. Chem., Int. Ed. Engl. 1969, 8, 535-622.
49. (a) The parent all-carbon six-electron electrocyclic orbital symmetry-forbidden conrotatory ring-opening reaction (1,3-cyclohexadiene → 1,3,5-hexatriene) has a computed reaction barrier of 57.5 kcal/mol (UB3LYP/6-31+G(d,p)) and a computed NICS(0) value of +21.9 (UB3LYP/6-311+G(2d,p) //(UB3LYP/6-31+G(d,p)). The same structure computed with a restricted closed shell configuration was found to have an RHF→UHF instability.
50. (b) For other recent examples where orbital symmetry-forbidden transition structures have been computed, see. De Proft, F.; Chattaraj, P. K.; Ayers, P. W.; Torrent-Sucarrat, M.; Elango, M.; Subramanian, V.; Giri, S.; Geerlings, P. J. Chem. Theory Comput. 2008, 4, 595-602;
51. Sakai, S. J. Phys. Chem. A 2006, 110, 6339-6344.
52. 13C NMR spectrum. The absence of TMS-trapped product A is consistent with an analogue of 6, rather than 7 occurring along the pathway to the diazocinone product for this particular system, although TMS migration (inter- or intramolecularly) cannot be ruled out. (Chemical Equation Presented)
53. These attempts included placing a phenyl group directly on C7, a CN group directly on C7, and CN groups directly on C3 and C8 (the tetrazine carbons). See Supporting Information for the structures we were able to locate and the corresponding energies.
54. The discussion here will be limited to the ring-opening pathways that are potentially available to these systems. For results related to the pyridazine-forming steps themselves (i.e., protonation and elimination of water), see the Supporting Information.
55. In general, synthesis of medium-sized rings tends to be relatively challenging. For reviews, see (a) Maier, M. E. Angew. Chem., Int. Ed. 2000, 39, 2073-2077.
56. (b) Yet, L. Chem. Rev. 2000, 100, 2963-3007.
57. The relative difference in energy here results in a fragmentation transition-state structure that is earlier than the competing electrocyclic process for the cyclooctanone derived system. See Supporting Information for these structures.
58. This ketone was also chosen because it has only one α-proton and is synthetically accessible.
59. The intermediate resulting from step (a) on the way to fused pyrazolines could potentially be protonated on the nitrogen (as shown) or on C8 to produce one of two possible diastereomeric products. Calculations on these possibilities for the system arising from 2,2,6-trimethylcyclohexanone reveal N-protonation to be thermodynamically favored over both C-protonation possibilities by approximately 11-16 kcal/mol.
60. (a) Pyrazoline derivatives have been shown to have interesting biological activities. For a recent example, see Frank, E.; Mucsi, Z.; Zupkó, I.; Réthy, B.; Falkay, G.; Schneider, G.; Wölfling, J. J. Am. Chem. Soc. 2009, 131, 3894-3904. Interestingly, pyrazoline derivatives have previously been found to result from the reaction of tetrazines with other enolate species, albeit through a different proposed mechanism.
61. See (b) Suen, Y. F.; Hope, H.; Nantz, M. H.; Haddadin, M. J.; Kurth, M. J. J. Org. Chem. 2005, 70, 8468-8471.
62. (c) Suen, Y. F.; Hope, H.; Nantz, M. H.; Haddadin, M. J.; Kurth, M. J. Tetrahedron Lett. 2006, 47, 7893-7896.