Mechanism of the Oxidation of Sulfides by Dioxiranes: Conformational Mobility and Transannular Interaction in the Oxidation of Thianthrene 5-Oxide Marı ´a Elena Gonza ´ lez-Nu ´n ˜ ez, † Rossella Mello, † Jorge Royo, † Gregorio Asensio,* ,† Isidro Monzo ´, ‡ Francisco Toma ´s, ‡ Jesu ´ s Garcı ´a Lo ´pez, § and Fernando Lo ´pez Ortiz § Departamento de Quı ´mica Orga ´ nica and Departamento de Quı ´mica Fı ´sica, Universidad de Valencia, Avda. V. Andre ´ s Estelle ´ s s/n, 46100-Burjassot (Valencia), Spain, and A Ä rea de Quı ´mica Orga ´ nica, Universidad de Almerı ´a, Carretera de Sacramento s/n, 04120 Almerı ´a, Spain gregorio.asensio@uv.es Received September 23, 2004 The detailed study of the oxidation of thianthrene 5-oxide (1) with methyl(trifluoromethyl)dioxirane (5b) in different solvents and in the presence of 18 O isotopic tracers is reported. Thianthrene 5-oxide (1) is a flexible molecule in solution, and this property allows for transannular interaction of the sulfoxide group with the expected zwitterionic 7 and hypervalent 10-S-4 sulfurane 9 intermediates formed in the oxidation and biases the course of the reaction toward the monooxygenation pathway. Introduction In studies of the oxidation of chemical and biochemical systems, it is very important to know the electronic character of the oxidant. Adam et al. 1 introduced the use of thianthrene 5-oxide (1) as a general mechanistic probe to determine the electrophilic or nucleophilic character of a given oxidant. With this probe, electrophilic oxidants should prefer to react with the sulfide moiety of 1 to yield disulfoxide 2, while nucleophilic oxidants should prefer- ably react at the sulfoxide sites of 1 and 2 to give sulfones 3 and 4, respectively (Scheme 1). Oxidants are classified as either electrophilic or nucleophilic according to the  SO value, a parameter defined by the ratio of oxidation at the SO site to total oxidation. The advantages claimed 1 for this mechanistic probe are the presence of sulfide and sulfoxide moieties in the same molecule, the lack of exchange in the oxidation products, and the existence of the probe molecule in a single geometry folded along the axis defined by the sulfur atoms and the pseudoequato- rial oxygen atom. Since the first report in 1984, 1d the mechanistic probe thianthrene 5-oxide has been used extensively to deter- mine the electronic nature of many classes of oxidants such as peroxometal complexes, 2 metalloporphyrin cata- lysts, 3 hemoprotein oxidizing species, 4 heteropolyoxo- metalate oxidants, 5 dimethylphenylsilylhydrotrioxide, 6 dialkylperoxonium intermediates, 7 carbonyl oxides, 1 per- acids, 8 dioxiranes, 9 and several metal oxidants. 10 † Departamento de Quı ´mica Orga ´ nica, Universidad de Valencia. ‡ Departamento de Quı ´mica Fı ´sica, Universidad de Valencia. § A Ä rea de Quı ´mica Orga ´ nica, Universidad de Almerı ´a. (1) (a) Adam, W.; Hass, W.; Lohray, B. B. J. Am. Chem. Soc. 1991, 113, 6202. (b) Adam, W.; Du ¨ rr, H.; Haas, W.; Lohray, B. B. Angew. Chem., Int. Ed. Engl. 1986, 25, 101. (c) Adam, W.; Lohray, B. B. Angew. Chem., Int. Ed. Engl. 1986, 25, 188. (d) Adam, W.; Haas, W.; Sieker, G. J. Am. Chem. Soc. 1984, 106, 5020. (2) (a) Bonchio, M.; Conte, V.; De Conciliis, M. A.; DiFuria, F.; Ballistreri, F. P.; Tommaselli, G. A.; Toscano, R. M. J. Org. Chem. 1995, 60, 4475. (b) Ballistreri, F. P.; Tommaselli, G. A.; Toscano, R. M.; Bonchio, M.; Conte, V.; DiFuria, F. Tetrahedron Lett. 1994, 35, 8041. (c) Ballistreri, F. P.; Tommaselli, G. A.; Toscano, R. M.; Conte, V.; DiFuria, F. J. Am. Chem. Soc. 1991, 113, 6209. (d) Adam, W.; Lohray, B. B. Angew. Chem., Int. Ed. Engl. 1986, 25, 188. (3) Akasaka, T.; Haranaka, M.; Ando, W. J. Am. Chem. Soc. 1991, 113, 9898. (4) Alvarez, J. C.; Ortiz de Montellano, P. R. Biochemistry 1992, 31, 8315. (5) Hamamoto, M.; Nakayama, K.; Nishiyama, Y.; Ishii, Y. J. Org. Chem. 1993, 58, 6421. (6) Plesnicar, B.; Cerkovnik, J.; Koller, J.; Kovac, F. J. Am. Chem. Soc. 1991, 113, 4946. (7) (a) Bloodworth, A. J.; Melvin, T.; Mitchell, J. C. In The Role of Oxygen in Chemistry and Biochemistry; Ando, W., Moro-oka, Y., Eds.; Studies in Organic Chemistry, Vol. 33; Elsevier. Amsterdam, 1988. (b) Bloodworth, A. J.; Melvin, T.; Mitchell, J. C. J. Org. Chem. 1988, 53, 1078. (8) (a) Erzen, E.; Koller, J.; Plesnicar, B. J. Org. Chem. 2001, 66, 5155. (b) Adam, W.; Golsch, D. J. Org. Chem. 1997, 62, 115. (9) Adam, W.; Chan, Y.-Y.; Cremer, D.; Gauss, J.; Sheutzow, D.; Shindler, M. J. Org. Chem. 1987, 52, 2800. (10) (a) Adam, W.; Corma, A.; Garcı ´a, H.; Weichold, O. J. Catal. 2000, 196, 339. (b) May, B. L.; Yee, H.; Lee, D. G. Can. J. Chem. 1994, 72, 2249. SCHEME 1. Thianthrene 5-Oxide Mechanistic Probe 9090 J. Org. Chem. 2004, 69, 9090-9099 10.1021/jo0483062 CCC: $27.50 © 2004 American Chemical Society Published on Web 12/01/2004