Photooxidation of Methyldithiepins into Dithiepin Carboxaldehydes in Carbon Tetrachloride

Methyldihydrodithiepins are converted into the corresponding carboxaldehydes via a simple and efficient oxidation by oxygen in carbon tetrachloride. The reaction is not a radical chain process. The proposed mechanism involves photoinduced electron transfer from the starting dithiepin to solvent (CCl4) followed by a series of events depicted in Scheme 1. The critical feature of the mechanism is that formation of superoxide (O2) is avoided, preventing direct oxidation of sulfur atoms. Benzylic photooxidations in the presence of electron-transfer (ET) sensitizers often provide a useful alternative to catalytic oxidation of methyl-substituted aromatics into aldehydes.1 Potentially, the advantage of such photo ET-based reactions over catalytic processes should be obvious for organosulfur substrates that are capable of poisoning the catalyst. Most commonly, however, photooxidation of sulfides and other SII organic species with oxygen is directed at the sulfur atom, leading to higher oxidation states of sulfur and/or C-S bond cleavage.2 Although generation of cation-radicals derived from an organosulfur compound is usually a simple and efficient process, the limited choice of end results diminishes the synthetic appeal of such reactions. Recently, we have been focusing our research efforts on the development of synthetically useful methods in which the generated sulfurcentered cation-radical is facilitating chemical changes in the molecule, besides S oxidation or C-S bond cleavage. Previously, we reported a photo-ET-induced C-C bond cleavage in hydroxyalkyl dithianes and its relevance to the development of photoremovable protecting groups for carbonyls.3 We now report our findings on photo-ET-induced oxidation of the methyl group in substituted dithiepins into a carbonyl, which is a rare example of a sulfide moiety surviving a photooxidation in the presence of molecular oxygen. We have found that irradiation (Pyrex filter) of 2-methyl3-phenyl-5,6-dihydro-1,4-dithiepin (1a) in CCl4 in the presence of oxygen furnished aldehyde 2a as the major product.4 Under nitrogen atmosphere no reaction occurred. We then synthesized a series of 3-aryl-substituted 2-methyl-1,4-dithiepins 1 and studied their photooxidation into (1) Julliard, M.; Galadi, A.; Chanon, M. J. Photochem. Photobiol., A: Chem. 1990 54, 79-90 and references therein. (b) Santamaria, J.; Jroundi, R. Tetrahedron Lett. 1991 32, 4291-4. (2) Most notably, such ET-initiated cleavages are used for photochemical deprotection of dithioacetals: (a) Schmittel, M.; Levis, M. Synlett 1996, 315-316. (b) Tanemura, K.; Dohya, H.; Imamura, M.; Suzuki, T.; Horaguchi, T. Chem. Lett. 1994, 965-8. (c) Kamata, M.; Murakami, Y.; Tamagawa, Y.; Kato, M.; Hasegawa, E. Tetrahedron 1994, 50, 12821-8. (d) Epling, G. A.; Wang, Q. Tetrahedron Lett 1992, 33, 5909-12. (e) Epling, G. A.; Wang, Q. Synlett 1992, 335-6. (3) McHale, W. A.; Kutateladze, A. G. J. Org. Chem. 1998, 63, 99249931. (4) All photooxidations were carried out with a medium-pressure Hg UV source in Pyrex tubes with bubbling oxygen. A 10 mM amount of 1a-g in carbon tetrachloride was used, and irradiations were carried out until complete conversion of the starting material was achieved. ORGANIC LETTERS 1999 Vol. 1, No. 6 937-939 10.1021/ol990870p CCC: $18.00 © 1999 American Chemical Society Published on Web 08/25/1999 carboxaldehydes 2 in carbon tetrachloride. As is evident from Table 1, most of the substrates we studied gave the corresponding aldehydes. Although the isolated yields of the aldehydes were moderate, the experimental simplicity and the mere fact that after irradiation the CCl4 solution contains >90% (by NMR) of the product greatly enhances the preparative value of the method. Dithiepins 1 are easily available from 2-methyl-1,3-dithiane 3 via the CoreySeebach dithiane-carbonyl adducts 45 with subsequent dehydration accompanied by ring expansion. Mechanistically significant results were obtained with p-methoxycarbonyl (1f) and p-cyano (1g) species. These dithiepins carrying an electron-withdrawing substituent were virtually unreactive. To rule out any radical chain process we ran a crossexperiment by irradiating a mixture of approximately 30% of (reactive) compound 1a and 70% of (unreactive) cyanosubstituted 1g. The production of 2a had slowed, and no 2g was observed. If anything, abstraction of a hydrogen atom from the methyl group in 1g is expected to be faster than it is in the unsubstituted 1a. However, we did not detect any 2g in the reaction mixture. Finally, a thermal reaction of 1a-g in the presence of radical initiators (AIBN or dibenzoyl peroxide) did not produce any amount of 2. We also ran the oxidative photolysis in the presence of methylene blue and detected no aldehyde formation. This ruled out the involvement of singlet oxygen in the photooxidation. Our fluorescence quenching experiments show that CCl4 does quench the fluorescence of compounds 1 in degassed acetonitrile solutions. Although the precise mechanism of this reaction is still under investigation, our experimental observations led us to the following mechanistic rationale (see Scheme 1). Carbon tetrachloride does not absorb light above the Pyrex filter cutoff, and therefore, it is the substrate 1 that is the primary light absorbing species, with the λmax ranging from 305 to 350 nm. After the initial excitation, single electron transfer occurs from the excited methyldithiepin moiety to a molecule of solvent producing a cation-radical/anion-radical pair, {1•+/ CCl4}. It is well established that CCl4 is unstable and falls apart into chloride anion and trichloromethyl radical,6 which is then intercepted by O2. In a detailed kinetic study, Alfassi and Mosseri7 had demonstrated that in carbon tetrachloride CCl3 reacts with molecular oxygen with k2 ≈ 1.12 × 105 M-1 s-1. The rate is not diffusion controlled, but a relatively high estimated oxygen concentration (approximately 12 mM in CCl4 with partial oxygen pressure 1 atm8) makes this pathway quite plausible in our case. 1•+ is then deprotonated by Cl-, and 1• radical recombines with CCl3O2, undergoes O-O bond cleavage, and produces the final aldehyde 2. Judging by the experimental and theoretical data accumulated in the literature, cation-radicals (e.g., of toluenes or methyl-substituted naphthalenes) are generally found to be superacids. For example, Arnold reported the pKa of the (5) For a review, see: Gröbel, B.-T.; Seebach, D. Synthesis 1977, 357402. (6) Chateauneuf, J.; Lusztyk, J.; Ingold, K. U. J. Org. Chem. 1990, 55, 1061-1065 and references therein. (7) Alfassi, Z. B.; Mosseri S. J. Phys. Chem. 1984, 88, 3296-3300. (8) Battino, R. Solubility Data Series: Vol. 7, Oxygen and Ozone; Pergamon: Oxford, England, 1981. Table 1