Selenium-Catalyzed Halolactonization: Nucleophilic Activation of Electrophilic Halogenating Reagents Shelli R. Mellegaard and Jon A. Tunge* Department of Chemistry, University of Kansas, Lawrence, Kansas 66045
[email protected] Received September 1, 2004
Abstract: Diphenyl diselenide catalyzes the halolactonization of unsaturated acids with N-halosuccinimides under mild conditions. The diselenide not only accelerates the reactions, but in some cases affords regiocontrol in favor of γ-lactone products. Experiments show that the regioselectivity in favor of γ-lactones is a result of kinetic rather than thermodynamic control.
In the years since its discovery in the early 1900s, halolactonization has proven to be a versatile reaction in organic synthesis, allowing facile formation of small or medium ring size lactones.1 The utility of the product halolactones has been repeatedly demonstrated by their use in total syntheses.2 The first reports of halolactonization utilized a weak base, KI, and molecular iodine1 for the cyclofunctionalization of unsaturated acids. Similarly, reagents such as N-bromosuccinimide,3 Br2,4 H2O2/ NaBr,5 CuBr2/Al2O3,6 Tl2CO3/Br2,7 and ZnBr2/Pb(OAc)48 have been shown to effect bromolactonization of unsaturated acids or carboxylates. Despite the utility of these reactions, control of the regio- and stereochemistry of the product bromolactones has not been properly addressed. With this in mind, it is particularly surprising that there are no reports of catalytic halolactonization. In this regard, it is noteworthy that Detty has developed a selenium-catalyzed protocol for halolactonization of unsaturated acids with H2O2/NaX;5 however, this method is best described as a catalytic oxidation of halides. While (1) (a) Bougault, J. Ann. Chim. Phys. 1908, 14, 145. (b) Bougault, J. Ann. Chim. Phys. 1908, 15, 296. (c) House, H. O. Modern Synthetic Reactions; W. A. Benjamin, Inc.: New York, 1972; p 441. (d) Dowle, M. D.; Davies, D. I.; Chem. Soc. Rev. 1979, 8, 171-197. (e) Cardillo, G.; Orena, M. Tetrahedron 1990, 46, 3321-3408. (2) (a) Murata, Y.; Kamino, T.; Aoki, T.; Hosokawa, S.; Kobayashi, S. Angew. Chem., Int. Ed. 2004, 43, 3175-3177. (b) Bodkin, J. A.; Humphries, E. J.; McLeod, M. D. Tetrahedron Lett. 2003, 44, 28692872. (c) Jung, M.; Ham, J.; Song, J. Org. Lett 2002, 4, 2763-2765. (d) Schultz, A. G.; Kirincich, S. J. J. Org. Chem. 1996, 61, 5626-5630. (e) Corey, E. J.; Trybulski, E. J.; Melvin, L. S., Jr.; Nicolaou, K. C.; Secrist, J. A.; Lett, R.; Sheldrake, P. W.; Falck, J. R.; Brunelle, D. J.; Haslanger, D. F.; Kim, S.; Yoo, S.-e. J. Am. Chem. Soc. 1978, 100, 4618-4620. (3) (a) Terashima, S.; Jew, S. Tetrahedron Lett. 1977, 11, 10051008. (b) Jew, S. Arch. Pharm. Res. 1982, 5, 97-101. (c) Cook, C.; Cho, Y.; Jew, S.; Suh, Y.; Kang, E. Arch. Pharm. Res. 1983, 6, 45-53. (4) Berti, B. Tetrahedron 1958, 4, 393-402. (5) (a) Drake, M. D.; Bateman, M. A.; Detty, M. R. Organometallics 2003, 22, 4158-4162. (b) Goodman, M. A.; Detty, M. R. Organometallics 2004, 23, 3016-3020. (6) Rood, G. A.; DeHaan, J. M.; Zibuck, R. Tetrahedron Lett. 1996, 37, 157-158. (7) Cambie, R. C.; Rutledge, P. S.; Somerville, R. F.; Woodgate, P. D. Synthesis 1988, 1009-1011. (8) Motohashi, S.; Satomi, M. Heterocycles 1985, 23, 2035-2039.
quite useful, the catalytic oxidation produces freely diffusing electrophilic bromine species and thus leaves little hope for control of selectivity. With the goal of catalytically halogenating organic substrates through nucleophilic activation of typical electrophilic halogen sources, we have turned to the use of similar selenium catalysts with “preoxidized” halogenating agents. Herein we report that simple arylselenides catalyze the halolactonization of unsaturated acids in the presence of Nhalosuccinimide oxidants. Furthermore, in some cases the use of selenium catalysts allows kinetic control of the regioselectivity and thus the lactone ring size. In an effort to develop catalytic halogenation reactions, we recently investigated the selenium-catalyzed allylic halogenation of β,γ-unsaturated acids (eq 1).9 While the
reaction was apparently general for alkyl-substituted olefins, upon switching to styrylacetic acid we discovered the ability of selenium reagents to catalyze halolactonizations. Specifically, trans-styrylacetic acid (R ) Ph) undergoes cyclization in the presence of phenylselenyl chloride and N-chlorosuccinimide to afford only the β-chloro-γ-lactone product (2). In the absence of PhSeCl,
