Stereochemistry of the Singlet Oxygenation of Simple Alkenes: A Stereospecific Transformation † Mariza N. Alberti, Georgios Vassilikogiannakis, and Michael Orfanopoulos* Department of Chemistry, UniVersity of Crete, 71003, Voutes-Heraklion, Crete, Greece orfanop@chemistry.uoc.gr Received July 1, 2008 ABSTRACT The stereochemistry of the allylic oxidation (ene reaction) mediated by singlet oxygen ( 1 O 2 ), using the optically active alkene (S,S)-cis-1,4- diphenyl-2-butene-1,4-d 2 , in MeOH and aprotic solvents was investigated. Our findings indicate that the title reaction is a highly stereospecific suprafacial process, independent of solvent polarity. The observation of an isotope effect, which matches the stereogenic ratio exactly, rules out biradical or open dipolar intermediates. Recent years have seen a burgeoning in research interest directed toward unraveling the chemistry of singlet oxygen ( 1 O 2 , 1 Δ g ). 1,2 This increased attention has been motivated by singlet oxygen’s environmental 3 and biological 4 impor- tance as well as its powerful synthetic potential. 5 Among the reactions of 1 O 2 with unsaturated substrates, 6 the ene or Schenk reaction 7 has received the most extensive experi- mental and theoretical attention. Several mechanisms have been postulated for this reaction. Although recent theoretical † This paper was presented in part at the 23rd International Conference on Photochemistry (ICP2007), Cologne, Germany, 29 July-3 August, 2007; Abstract No. IL-13, p 169. (1) (a) Wasserman, H. H.; Murray, R. W. Singlet Oxygen; Academic Press: New York, 1979. (b) Frimer, A. A.; Stephenson, L. M. In Singlet Oxygen. Reactions, Modes and Products; Frimer, A. A., Ed.; CRC Press, Boca Raton, FL, 1985. (c) Foote, C. S.; Clennan, E. L. In ActiVe Oxygen in Chemistry; Foote, C. S., Valentine, J. S., Greenberg, A., Liebman, J. F., Eds.; Chapman and Hall: London, 1995; pp 105-140. (2) For the effect of strain on 1 O 2 reactions, see: (a) Frimer, A. A.; Weiss, J. J. Org. Chem. 1993, 58, 3660–3667. (b) Frimer, A. A.; Weiss, J.; Gottlieb, H. E.; Wolk, J. L. J. Org. Chem. 1994, 59, 780–792. (c) Frimer, A. A.; Afri, M.; Baumel, S. D.; Gilinsky-Sharon, P.; Rosenthal, Z.; Gottlieb, H. E. J. Org. Chem. 2000, 65, 1807–1817. (d) Sharon, O.; Frimer, A. A. Tetrahedron 2003, 59, 8153–8162. (3) (a) Ranby, B.; Rabek, J. F. Photodegradation, Photooxidation and Photostabilization of Polymers; Wiley: London, 1975. (b) Abdou, M. S. A.; Holdcroft, S. Macromolecules 1993, 26, 2954–2962. (c) Scurlock, R. D.; Wang, B.; Ogilby, P. R.; Sheats, J. R.; Clough, R. L. J. Am. Chem. Soc. 1995, 117, 10194–10202. (4) (a) Gollnick, K.; Hartmann, H. Oxygen and Oxy Radicals in Biology; Academic Press, New York, 1981; pp. 379-395. (b) Wentworth, P. J.; Jones, L. H.; Wentworth, A. D.; Zhu, X.; Larsen, N. A.; Wilson, I. A.; Xu, X.; Goddard, W. A., III; Janda, K. D.; Eschenmoser, A.; Lerner, R. A. Science 2001, 293, 1806–1809. (c) Wentworth, P. J.; McDunn, J.; Wentworth, A. D.; Takeuchi, C.; Nieva, J.; Janda, K. D.; Eschenmoser, A.; Lerner, R. A. Science 2002, 298, 2195–2199. (d) Davies, M. J. Biochem. Biophys. Res. Commun. 2003, 305, 761–770. (e) Chin, K. K.; Trevithick-Sutton, C. C.; McCallum, J.; Jockusch, S.; Turro, N. J.; Scaiano, J. C.; Foote, C. S.; Garcia- Garibay, M. A. J. Am. Chem. Soc. 2008, 130, 6912–6913. (5) (a) Hoffmann, N. Chem. ReV 2008, 108, 1052–1103, and references cited therein. (b) Griesbeck, A. G.; Blunk, D.; El-Idreesy, T. T.; Raabe, A. Angew. Chem., Int. Ed. 2007, 46, 8883–8886. (c) Griesbeck, A. G.; El- Idreesy, T. T. Tetrahedron 2006, 62, 10615–10622. (d) Montagnon, T.; Tofi, M.; Vassilikogiannakis, G. Acc. Chem. Res. 2008, 41, 1001–1011. (e) Margaros, I.; Montagnon, T.; Tofi, M.; Pavlakos, E.; Vassilikogiannakis, G. Tetrahedron 2006, 62, 5308–5317. (f) Georgiou, T.; Tofi, M.; Montag- non, T.; Vassilikogiannakis, G. Org. Lett. 2006, 8, 1945–1948. (g) Vassilikogiannakis, G.; Margaros, I.; Montagnon, T.; Stratakis, M. Chem. Eur. J. 2005, 11, 5899–5907. (6) For singlet oxygen [2 + 2] and [4 + 2] cycloadditions, see: (a) Adam, W.; Prein, M. Acc. Chem. Res. 1996, 29, 275–283. (b) Iesce, M. R. Photooxygenation of the [4 + 2] and [2 + 2] Type In Synthetic Organic Photochemistry; Griesbeck, A. G., Mattay, J., Ed.; Marcel Dekker: New York, 2005; pp 299-363. ORGANIC LETTERS 2008 Vol. 10, No. 18 3997-4000 10.1021/ol801488w CCC: $40.75  2008 American Chemical Society Published on Web 08/16/2008