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The Arene-Alkene meta-Photocycloaddition Reaction
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    Introduction:

    Our research program focuses on developing methods to make organic synthesis practical and efficient. Our ultimate objective is the ideal synthesis: making complex molecules from simple starting materials in one step and 100% yield in a manner that is operationally simple, fast, safe, environmentally acceptable, and resource efficacious. To achieve this formidable goal we are working on developing reactions that rapidly build complexity in a synthesis.

    The arene-alkene photocycloaddition has the potential to meet the criteria for the ideal synthesis (Figure 1). It uses simple, readily available starting materials and in one operation can create up to 3 new rings and 6 new stereocenters with the added benefit that one can easily convert the products to synthetically significant targets. Because the reactant is light, there are no toxic reagents to store and no toxic waste materials to dispose of making the reaction environmentally friendly. The three-step synthesis of silphinene (Figure 2) illustrates the remarkable power of this reaction and serves as a measure to determine how close we are to the ideal synthesis. In addition to silphinene, many other complex molecules have been synthesized using this method (Figure 3).

    Figure 1
    Figure 2

    Mechanism of the Photocycloaddition [17]:

    Figure 3
    Figure 4

     

    Selectivity Issues [18]:

    Figure 5

    Projects:

    A number of triquinanes have been synthesized using the intramolecular arene-alkene photocycloaddition reaction, but the utility of the reaction has never been expanded to include a tetraquinanyl structure.

    In 1978 Steglich and coworkers isolated from the basidiomycetous fungus Crinipellis stipitaria a group of natural products showing activity against Gram-positive bacteria, yeasts, and filamentous fungi [20]. Several years later they elucidated the structures of three biologically active crinipellins: crinipellin A, O-acetylcrinipellin A, and crinipellin B [21] (Figure 6). Early in 1993 Piers reported the first synthesis of a crinipellin; starting from 2-methylcyclopent-2-enone crinipellin B was synthesized in 22 steps [22].

    Our current synthetic efforts focus on synthesizing Crinipellin A using the arene-alkene meta-photocycloaddition reaction.

    Figure 6

    References:

    1. Wender, P. A.; Siggel, L.; Nuss, J. M. [3+2] and [5+2] Arene-Alkene Photocycloadditions, In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Paquette, L. A., Eds.; Pergamon: Elmsford, NY, 1991, Vol. 5, p. 645. Cornelisse, J. Chem. Rev. 1993, 93, 615. Wender, P. A.; Dore T. M. "Intra- and Intermolecular Cycloadditions of Benzene Derivatives." In Handbook of Organic Photochemistry and Photobiology; Horspool, W. S.; Song, P. -S., Eds.; CRC Press Inc: Boca Raton, FL. 1995, pp. 277-86. In Press.
    2. Wender, P. A.; Ternansky, R. J. Tetrahedron Lett. 1985, 26, 2625.
    3. Wender, P. A.; Howbert, J. J. J. Am. Chem. Soc. 1981, 103, 688. Wender, P. A.; Howbert, J. J.; Dore, T. M. "The Total Synthesis of ±-œ-Cedrene." In Photochemical Key Steps in Organic Synthesis ; Mattay, J.; Griesbeck, A. G., Eds.; VCH Verlagsgesellschaft: Weinheim, Germany, 1994, pp. 181-185.
    4. Howbert, J. J. Ph.D. Dissertation, Harvard University, 1983.
    5. Wender, P. A.; Dreyer, G. Tetrahedron 1981, 37, 4445.
    6. Wender, P. A.; Howbert, J. J. Tetrahedron Lett. 1982, 23, 3983.
    7. Wender, P. A.; Howbert, J. J. Tetrahedron Lett. 1983, 24, 5325.
    8. Wender, P. A.; Fisher, K. Tetrahedron Lett. 1986, 27, 1857.
    9. Wender, P. A.; Dreyer, G. J. Am. Chem. Soc. 1982, 104, 5805.
    10. Wender, P. A.; Dreyer, G. Tetrahedron Lett. 1983, 24, 4543.
    11. Wender, P. A.; Singh, S. Tetrahedron Lett. 1985, 26, 5987.
    12. Wolanin, D. Ph.D. Dissertation, Harvard University, 1982.
    13. Wender, P. A.; Singh, S. Tetrahedron Lett. 1990, 31, 2517.
    14. Wender, P. A.; von Geldern, T. W.; Levine, B. H. J. Am. Chem. Soc. 1988, 110, 4858.
    15. Wender, P. A.; deLong, M. A. Tetrahedron Lett. 1990, 31, 5429.
    16. Mani, J.; Sch��ttel, S.; Zhang, C.; Bigler, P.; M��ller, C.; Keese, R. Helv. Chim. Acta 1989, 72, 487. Mani, J.; Keese, R. Tetrahedron 1985, 41, 5697. deLong, M. A. Ph.D. Dissertation, Stanford University, 1992.
    17. See reference 1 and references cited therein.
    18. See reference 1 and references cited therein.
    19. Sugimura, T.; Nishiyama, N.; Tai, A. Tetrahedron: Asymmetry 1994, 5, 1163.
    20. Kupka, J.; Anke, T.; Oberwinkler, F.; Schramm, G.; Steglich, W. J. Antibiotics 1979, 32, 130.
    21. Anke, T.; Heim, J.; Knoch, F.; Mocek, U.; Steffen, B.; Steglich, W. Angew. Chem. Int. Ed. Engl. 1985, 24, 709.
    22. Piers, E.; Renaud, J. J. Org. Chem. 1993, 58, 11.
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