IJOC  Vol.3 No.3 , September 2013
Computational Study of the Cyclization of 5-Hexenyl, 3-Oxa-5-Hexenyl and 4-Oxa-5-Hexenyl Radicals
ABSTRACT
The intramolecular cyclization of 5-hexenyl radicals continues to be an important synthetic method for the construction of five-membered rings. The synthetic utility arises from the high degree of regioselectivity to give predominantly cyclopentyl products in high yield under mild conditions. Recently we reported product cyclization studies on 4-oxa perturbed 5-hexenyl radical. In this paper, we report our results from a computational study (UB3LYP and UCCSD (T)) of the cyclization of a series of 5-hexenyl and 3-and 4-oxa-5-hexenyl radicals. Three highly conserved cyclization tran-sitions states (exo-chair, exo-boat and endo-chair) were located for 10 acyclic radicals. Activation energies were calcu-lated for the three modes of cyclization for each radical. Calculated values for the exo/endo cyclization ratios had a high level of agreement with experiment and predictions were offered for two cases that have not been experimentally tested. The increased percentage of exo-cyclization with 3-and 4-oxa substitution is the result of an increase in the energy dif-ference between the exo-and endo-chair transition states compared to the hydrocarbon systems. The decreased rate of cyclization of the 4-oxa compounds is primarily due to the stabilization of the initial acyclic radical by the vinyl ether linkage. The increase in the rate of cyclization with 3-methyl substitution is due to the increased conformational energy of the starting acyclic radical.

Cite this paper
A. Matlin and M. Leyden, "Computational Study of the Cyclization of 5-Hexenyl, 3-Oxa-5-Hexenyl and 4-Oxa-5-Hexenyl Radicals," International Journal of Organic Chemistry, Vol. 3 No. 3, 2013, pp. 169-175. doi: 10.4236/ijoc.2013.33021.
References
[1]   Z. Pianowski, L. Rupnicki, P. Cmoch and K. Stalinski, “Radical Cyclizations Leading to the Bicyclo[2.2.1]heptane Framework: A New Radical Approach to (+-(Z)-β-Santalol,” Synthetic Letters, Vol. 2005, No. 6, 2005, pp. 900-904.

[2]   C. Zhou, O. Plashkevych and J. Chattopadhyaya, “Unusual Radical 6-Endo Cyclization to Carbocyclic-ENA and Elucidation of its Solution Conformation by 600 MHz NMR and Ab Initio Calculations,” Organic & Bio-molecular Chemistry, Vol. 6, No. 24, 2008, pp. 4627-4633. doi:10.1039/b813870b

[3]   J. Hartung, R. Kneuer, C. Rummey and G. Bringmann, “On the 6-Endo Selectivity in 4-Penten-1-oxyl Radical Cyclizations,” Journal of the American Chemical Society, Vol. 126, No. 38, 2004, pp. 12121-12129. doi:10.1021/ja049010g

[4]   J. C. Tripp, C. H. Schiesser and D. S. Curran, “Stereochemistry of Hexenyl Radical Cyclizations with tert-Butyl and Related Large Groups: Substituent and Temperature Effects,” Journal of the American Chemical Society, Vol. 127, No. 15, 2005, pp. 5518-5527.

[5]   O. Moriya, Y. Urata, Y. Ikeda, Y. Ueno and T. Endo, “Synthesis of Tetrahydrofurans from Active Methylene Compounds via Radical Cyclization.” Journal of Organic Chemistry, Vol. 51, No. 24, 1986, pp. 4708-4709. doi:10.1021/jo00374a038

[6]   S. J. Gharpure and S. K. Porwal, “Tandem Radical Cyclization-based Strategy for the Synthesis of Oxaand Aza-Cages: A Case of Fragmentation Versus Cyclization,” Tetrahedron Letters, Vol. 51, No. 25, 2010, pp. 3324-3329. doi:10.1016/j.tetlet.2010.04.081

[7]   W. Du and D. P. Curran, “Synthesis of Carbocyclic and Heterocyclic Fused Quinolones by Cascade Radical Annulations of Unsaturated N-arylthiocarbamates, Thioamides and Thioureas,” Organic Letters, Vol. 5, No. 10, 2003, pp. 1765-1768. doi:10.1021/ol0344319

[8]   B. M. Trost, H. C. Shen and J. P. Surivet, “Biomimetic Enantioselective Total Synthesis of (-)-Siccanin via the Pd-catalyzed Asymmetric Allylic Alkylation (AAA) and Sequential Radical Cyclization,” Journal of the American Chemical Society, Vol. 126, No. 39 2004, pp. 12565-12579. doi:10.1021/ja048084p

[9]   G. A. Kraus and J. Kim, “Synthesis of the Teracyclic Ring System of Cumbiasin A (II) via Tandem Radical Cyclizations,” Tetrahedron Letters, Vol. 47, No. 44, 2006, pp. 7797-7799. doi:10.1016/j.tetlet.2006.08.081

[10]   A. L. J. Beckwith, C. J. Easton and A. K. Serellis. “Some Guidelines for Radical Reactions.” Journal of the Chemical Society, Chemical Communications, No. 11, 1980, pp. 482-483. doi:10.1039/c39800000482

[11]   B. Giese, “Formation of CC Bonds by Addition of Free Radicals to Alkenes,” Angewandte Chemie International Edition English, Vol. 22, No. 10, 1983, pp. 753-764. doi:10.1002/anie.198307531

[12]   J. M. Tedder and J. C. Walton, “The Importance of Polarity and Steric Effects in Determining the Rate and Orientation of Free Radical Addition to Olefins,” Tetrahedron, Vol. 36, No. 6, 1980, pp. 701-707. doi:10.1016/S0040-4020(01)93680-4

[13]   A. L. J. Beckwith and C. H. Schiesser, “Regio-and Ste-reo-Selectivity of Alkenyl Radical Ring Closure: A The oretical Study,” Tetrahedron, Vol. 41, No. 19, 1985, pp. 3925-3941. doi:10.1016/S0040-4020(01)97174-1

[14]   A. L. J. Beckwith and C. H. Schiesser. “A Force-Field Study of Alkenyl Radical Ring Closure,” Tetrahedron Letters, Vol. 26, No. 3, 1985, pp. 373-376. doi:10.1016/S0040-4039(01)80821-2

[15]   D.C. Spellmeyer and K. N. Houk, “A Force-Field Model for Intramolecular Radical Additions,” Journal of Organic Chemistry, Vol. 52, No. 6, 1987, pp. 959-977. doi:10.1021/jo00382a001

[16]   A. G. Leach, R. Wang, G. E. Wohlhieter, S. I. Khan, M. E. Jung and K. N. Houk, “Theoretical Elucidation of Kinetic and Thermodynamic Control of Radical Addition Regioselectivity,” Journal of the American Chemical Society, Vol. 125, No. 14, 2003, pp. 4271-4278. doi:10.1021/ja029342q

[17]   D. Shanks, S. Berlin, M. Besev, H. Ottosson and L. Engman, “On the Origin of cis Selectivity in the Cyclization of N-protected 2-Substituted 3-Aza-5-Hexenyl Radicals: A Density Functional Study,” Journal of Organic Chemistry, Vol. 69, No. 5, 2004, pp. 1487-1491. doi:10.1021/jo030294h

[18]   P. d’Antuno, A. Fritsch, L. Ducasse, F. Castet, P. James and Y. Landias, “Theoretical Study of Free-Radical-Mediated 5-Exo-Trig Cyclizations of Chiral 3-Substituted Hepta-1,6-dienes,” Journal of Physical Chemistry A, Vol. 110, No. 10, 2006, pp. 3714-3722. doi:10.1021/jp0549531

[19]   C. W. Wu and J. J. Ho, “Calculated Effect of Subsitutions on the Regioselectivity of Cyclization of α-Sulfenyl-, α-Sulfinyl-, and α-Sulfonyl-(5R)-5-Hexenyl Radicals,” Journal of Organic Chemistry, Vol. 71, No. 26, 2006, pp. 9595-9601. doi:10.1021/jo061614a

[20]   A. R. Matlin, K. F. Brinton and B. T. Nivaggioli, “Rule of Five Cyclizations in 5-Hexenyl Radicals and Photocycloadditions of 1,5-Hexadienes: Effect of 4-Oxa Substitution,” Journal of Physical Organic Chemistry, Vol. 20, No. 2, 2007, pp. 83-87. doi:10.1002/poc.1120

[21]   Spartan08, Wavefunction Inc., Y. Shao, L. F. Molnar, Y. Jung, J. Kussmann, C. Ochsenfeld, S. T. Brown, A. T. B. Gilbert, L. V. Slipchenko, S. V. Levchenko, D. P. O’Neill, R. A. DiStasio Jr., R. C. Lochan, T. Wang, G. J. O. Beran, N. A. Besley, J. M. Herbert, C. Y. Lin, T. Van Voorhis, S. H. Chien, A. Sodt, R. P. Steele, V. A. Rassolov, P. E. Maslen, P. P. Korambath, R. D. Adamson, B. Austin, J. Baker, E. F. C. Byrd, H. Dachsel, R. J. Doerksen, A. Dreuw, B. D. Dunietz, A. D. Dutoi, T. R. Furlani, S. R. Gwaltney, A. Heyden, S. Hirata, C.-P. Hsu, G. Kedziora, R. Z. Khalliulin, P. Klunzinger, A. M. Lee, M. S. Lee, W. Z. Liang, I. Lotan, N. Nair, B. Peters, E. I. Proynov, P. A. Pieniazek, Y. M. Rhee, J. Ritchie, E. Rosta, C. D. Sherrill, A. C. Simmonett, J. E. Subotnik, H. L. Woodcock III, W. Zhang, A. T. Bell, A. K. Chakraborty, D. M. Chipman, F. J. Keil, A. Warshel, W. J. Hehre, H. F. Schaefer, J. Kong, A. I. Krylov, P. M. W. Gill and M. Head-Gordon, “Advances in Methods and Algorithms in a Modern Quantum Chemistry Program Package,” Physical Chemistry Chemical Physics, Vol. 8, No. 27, 2006, pp. 3172-3191.

[22]   M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, J. A. Montgomery, Jr., T. Vreven, K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratchian, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, P. Y. Ayala, K. Morokuma, G. A. Voth, P. Salvador, J. J. Dannenberg, V. G. Zakrzewski, S. Dapprich, A. D. Daniels, M. C. Strain, O. Farkas, D. K. Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. V. Ortiz, Q. Cui, A. G. Baboul, S. Clifford, J. Cioslowski, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. L. Martin, D. J. Fox, T. Keith, M. A. AlLaham, C. Y. Peng, A. Nanayakkara, M. Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M. W. Wong, C. Gonzalez and J. A. Pople, “Gaussian 03 Revision E.01,” Gaussian 03, Revision E.01, Gaussian, Inc., Wallingford, 2004.

[23]   C. Walling and A. Cioffari, “Cyclizations of 5-Hexenyl Radicals,” Journal of the American Chemical Society, Vol. 94, No. 17, 1972, pp. 6059-6064. doi:10.1021/ja00772a020

[24]   A. L. J. Beckwith, T. Lawrence and A. K. Serelis, “Stereoselectivity of Ring Closure of Substituted Hex-5-enyl Radicals,” Journal of the Chemical Society, Chemical Communications, Vol. 1980, No. 11, 1980, pp. 484-485. doi:10.1039/c39800000484

[25]   A. L. J. Beckwith and S. A. Glover, “Determination of the Rates for Ring Closure of Oxygen Containing analogues of Hex-5-enyl Radicals by Kinetic E.S.R. Spectroscopy,” Australian Journal of Chemistry, Vol. 4, No. 1, 1987, pp. 157-173. doi:10.1071/CH9870157

[26]   T. W. Smith and G. H. Butler, “Effect of Substituents on Ring Size in Radical Cyclizations. 1. Methyl vs. Phenyl,” Journal of Organic Chemistry.” Vol. 43, No. 1, 1978, pp. 6-13. doi:10.1021/jo00395a002

[27]   E. L. Eliel, N. L. Allinger, S. J. Angyal and G. A., Morrison, “Conformational Analysis,” Wiley, New York, 1965, p. 191.

 
 
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