Mechanistic Course of the Asymmetric Methoxyselenenylation Reaction Thomas Wirth,* Gianfranco Fragale, and Martin Spichty Contribution from the Institut fu ¨ r Organische Chemie der UniVersita ¨ t Basel, St. Johanns-Ring 19, CH-4056 Basel, Switzerland ReceiVed December 9, 1997 Abstract: In alkoxyselenenylation reactions of alkenes intermediate seleniranium ions 1 are formed. In competition experiments it was shown that the formation of these intermediates is reversible. The seleniranium ions of type 20 + formed by addition of chiral selenium electrophiles to alkenes are the decisive intermediates in the asymmetric methoxyselenenylation reaction. Their stabilities are strongly dependent on the strength of the selenium-heteroatom interaction. This was shown experimentally, because an independent method has been used for the synthesis of different diastereomeric seleniranium ions. Furthermore, calculations have been carried out to determine the relative stabilities of the diastereomeric seleniranium ions 20 + . The results obtained from the calculations support the experimental findings. Introduction The stereoselective functionalization of nonactivated CdC double bonds is still a great challenge in asymmetric synthesis. Beside stoichiometric reactions, only few catalytic variants have been developed up to now. 1 Stoichiometric addition reactions with chiral reagents deserve further investigations. In recent times organoselenium compounds gained an increasing popular- ity in organic chemistry because of their mild and selective reactions. 2 Electrophilic selenium reagents are often utilized for the functionalization of double bonds. The addition of selenium electrophiles to alkenes leads to seleniranium ions 1 as heterocyclic three-membered ring intermediates. These seleniranium ions are then attacked by a nucleophile from the anti side leading to addition products 2 (Scheme 1). The selenides 2 are versatile building blocks for subsequent reactions. A homolytic cleavage of the carbon- selenium bond generates radicals and is the entry into radical chemistry. Oxidation of the selenide to the selenoxide and -hydride elimination can again introduce double bonds into the molecule, which are then functionalized in the allylic position. Furthermore, deprotonation in R-position to the selenium can be used for carbanionic chemistry. Recently we 3 and other research groups 4-7 developed chiral selenium compounds which are versatile reagents in asymmetric addition reactions to alkenes. A wide variety of different alkenes can be employed. Therefore, asymmetric -alkoxyse- lenenylation reactions are possible as well as intramolecular selenolactonizations, selenoetherifications, or aminoselenen- ylations leading to addition or cyclization products with high stereoselectivities. We already have established the versatility of such addition products as potent building blocks in enantio- selective synthesis of various natural products. 8 (1) (a) For asymmetric dihydroxylation, see: Kolb, H. C.; VanNieu- wenhze, M. S.; Sharpless, K. B. Chem. ReV. 1994, 94, 2483-2547. (b) For asymmetric epoxidation see: Jacobsen, E. N. In ComprehensiVe Organo- metallic Chemistry II; Wilkinson, G., Stone, F. G. A., Abel, E. W., Hegedus, L. S., Eds.; Pergamon Press: New York, 1995; Vol. 12, Chapter 11.1. (2) (a) Nicolaou, K. C.; Petasis, N. A. Selenium in Natural Products Synthesis; CIS: Philadelphia, 1984. (b) Paulmier, C. Selenium Reagents and Intermediates in Organic Synthesis; Pergamon: Oxford, 1986; pp 319- 322. (c) Organoselenium Chemistry; Liotta, D., Ed.; Wiley: New York, 1987. (d) Hargittai, I.; Rozsondai, B. The Chemistry of Organic Selenium and Tellurium Compounds; Patai, S., Ed.; Wiley: Chichester, U.K., 1987; Vol. 1, Chapter 3. (3) (a) Wirth, T. Angew. Chem. 1995, 107, 1872-1873; Angew. Chem., Int. Ed. Engl. 1995, 34, 1726-1728. (b) Wirth, T.; Fragale, G. Chem. Eur. J. 1997, 3, 1894-1902. (c) Review: Wirth, T. Liebigs Ann./Recl. 1997, 2189-2196. (4) (a) Nishibayashi, Y.; Singh, J. D.; Uemura, S.; Fukuzawa, S. Tetrahedron Lett. 1994, 35, 3115-3118. (b) Nishibayashi, Y.; Srivastava, S. K.; Takada, H.; Fukuzawa, S.; Uemura, S. J. Chem. Soc., Chem. Commun. 1995, 2321-2322. (c) Review: Nishibayashi, Y.; Uemura, S. ReV. Heteroatom Chem. 1996, 14, 83-118. (d) Fukuzawa, S.; Takahashi, K.; Kato, H.; Yamazaki, H. J. Org. Chem. 1997, 62, 7711-7716. (5) (a) De ´ziel, R.; Goulet, S.; Grenier, L.; Bordeleau, J.; Bernier, J. J. Org. Chem. 1993, 58, 3619-3621. (b) De ´ziel, R.; Malenfant, E. J. Org. Chem. 1995, 60, 4660-4662. (c) De ´ziel, R.; Malenfant, E.; Be ´langer, G. J. Org. Chem. 1996, 61, 1875-1876. (d) De ´ziel, R.; Malenfant, E.; Thibault, C.; Fre ´chette, S.; Gravel, M. Tetrahedron Lett. 1997, 38, 4753-4756. (6) (a) Tomoda, S.; Fujita, K.; Iwaoka, M. J. Chem. Soc., Chem. Commun. 1990, 129-131. (b) Fujita, K.; Iwaoka, M.; Tomoda, S. Chem. Lett. 1992, 1123-1124. (c) Tomoda, S.; Fujita, K.; Iwaoka, M. Phosphorus Sulfur 1992, 67, 247-252. (d) Fujita, K.; Murata, K.; Iwaoka, M.; Tomoda, S. Tetrahedron Lett. 1995, 36, 5219-5222. (e) Fujita, K.; Murata, K.; Iwaoka, M.; Tomoda, S. J. Chem. Soc., Chem. Commun. 1995, 1641-1642. (f) Fujita, K.; Murata, K.; Iwaoka, M.; Tomoda, S. Tetrahedron 1997, 53, 2029-2048. (g) Review: Fujita, K. ReV. Heteroatom Chem. 1997, 16, 101- 117. (7) (a) Back, T. G.; Dyck, B. P.; Parvez, M. J. Org. Chem. 1995, 60, 703-710. (b) Back, T. G.; Dyck, B. P. J. Chem. Soc., Chem. Commun. 1996, 2567-2568. (8) (a) Wirth, T.; Kulicke, K. J.; Fragale, G. J. Org. Chem. 1996, 61, 2686-2689. (b) Wirth, T. Liebigs Ann./Recl. 1997, 1155-1158. (c) Wirth, T.; Fragale, G. Synthesis 1998, 162-166. Scheme 1 3376 J. Am. Chem. Soc. 1998, 120, 3376-3381 S0002-7863(97)04177-2 CCC: $15.00 © 1998 American Chemical Society Published on Web 03/25/1998