Triphenyl Phosphite Ozonide1

(PhO)3PO3

[29833-83-8]  · C18H15O6P  · Triphenyl Phosphite Ozonide  · (MW 358.30)

(source of singlet oxygen;2 avoids complicating effects of radiation on reactants and products sometimes associated with photochemical generation of singlet oxygen; can also transfer dioxygen in a bimolecular process3 not involving singlet oxygen)

Physical Data: reagent is labile and is prepared and used in situ.

Solubility: sol dichloromethane, carbon tetrachloride, benzene, acetonitrile, trichlorofluoromethane, toluene, chlorobenzene, methanol, isopropyl alcohol, acetone, diethyl ether, and pyridine.

Form Supplied in: reagent is prepared as needed.

Analysis of Reagent Purity: 31P NMR.

Preparative Methods: a solution of triphenyl phosphite in CH2Cl2 is added to O3-saturated (blue color) CH2Cl2 at -78 °C. Ozone is added periodically in order to maintain the blue color. The alternative procedure of adding ozone to a solution of the triphenyl phosphite in CH2Cl2 leads to lower yields of the ozonide since the phosphite reacts with the ozonide. When the ozonide is to be used as a source of singlet oxygen the solution is allowed to warm to about -25 °C in the presence of the substrate. Direct transfer of dioxygen in a bimolecular process occurs at -70 °C.2,4,5

Handling, Storage, and Precautions: decomposes with O2 evolution at temperatures above about -25 °C. While solid triphenyl phosphite ozonide has occasionally been isolated1b,6-8 this procedure is not recommended since the solid has been observed1b,7,8 to detonate, with flashes of red light, upon warming.

Use as Singlet Oxygen Source.

In 1959, Knowles and Thompson4 showed that Ozone forms a 1:1 adduct with Triphenyl Phosphite at low temperatures and that this adduct decomposes, with gas evolution, as the reaction solution is allowed to warm up. Corey9 suggested that the oxygen evolved might be singlet oxygen. Experiments to investigate this possibility were initiated by Murray and co-workers in 1967. In collaboration with Wasserman and Yager6 they were able to show that the gas evolved from solid triphenyl phosphite ozonide gave the characteristic ESR signal of singlet oxygen. Chemical evidence for the involvement of singlet oxygen was obtained by demonstrating that typical singlet oxygen products were obtained2 from a variety of substrates when exposed to decomposing triphenyl phosphite ozonide (1). Thus 1,3-cyclohexadiene was converted to the endoperoxide in 67% yield (eq 1). The ene reaction was observed when 2,3-dimethyl-2-butene was converted to 2,3-dimethyl-3-hydroperoxy-1-butene in 53% yield by (1) (eq 2). Another example of a 1,4-cycloaddition reaction was observed in the transformation of tetraphenylcyclopentadienone to cis-dibenzoylstilbene in 38.2% yield. Likewise, a-terpinene was converted to ascaridole in 60% yield. Finally, in this earlier work, 9,10-diphenylanthracene was converted in 77% yield to its endoperoxide.

Similar work by Bartlett and Mendenhall10 showed that (1) converts9,10 dimethylanthracene (49%) and rubrene (87%) to their respective endoperoxides. When the singlet oxygen acceptor 1,3-diphenylisobenzofuran was oxidized10 by (1), a 16% yield of the singlet oxygen product o-dibenzoylbenzene was obtained accompanied by an oxygen-1,3-diphenylisobenzofuran copolymer (eq 3).

The third major reaction type ascribed to singlet oxygen has also been achieved using (1) as the singlet oxygen source. In this case, 2,2-adamantylideneadamantane was converted to the dioxetane (eq 4).11

Dioxetane intermediates also seem to be involved in the conversion of 1-(2-methoxyvinyl)pyrene and 1,1-diphenyl-2-methoxyethylene to their cleavage products.12 Dioxetane-type intermediates have also been invoked13 in the reaction between (1) and several ketenes. The reaction of the tetrathioethylene (2) with (1) is also believed14 to proceed through the dioxetane. The products are the disulfide (3) and the dithiooxalate (4) (eq 5).

Additional evidence that (1) is a source of singlet oxygen was obtained by using substrates in which known singlet oxygen reactions proceed to give a characteristic product distribution. The reaction of (1) with 2-methyl-2-butene gives15 two hydroperoxides with the distribution shown (eq 6). The observed ratio is not significantly different from that obtained when other sources of singlet oxygen are used. Singlet oxygen product ratios were also obtained15,16 by two groups when the substrate is 1,2-dimethylcyclohexene. Kopecky et al.17 showed that reaction of isopropylidenecyclohexane with (1) gives two hydroperoxide products in a ratio which is closer to that given in a reaction believed to involve singlet oxygen and quite different from that obtained in a base-catalyzed displacement reaction of the appropriate b-halohydroperoxide.

Triphenyl phosphite ozonide has been used18 in an unusual synthesis of the trans-triepoxide of benzene from oxepin (eq 7). A somewhat different type of singlet oxygen reaction is observed19 when 2,6-di-t-butylphenol is treated with (1). In this case the product p-benzoquinone and diphenoquinone (eq 8) are believed to be formed from radicals arising from an initial H-atom abstraction reaction of singlet oxygen with the phenol.

Treatment of Wittig reagents with (1) gives the expected aldehyde.20 In an unusual application of this procedure, a trimethylsilyl-substituted Wittig reagent is oxidized to a trimethylsilyl ketone. A bis(trimethylsilyl) Wittig reagent gives the corresponding ketone when oxidized by (1) (eq 9). This ketone can be used to introduce carbonyl groups. Disulfides are converted21 to mixtures of thiosulfinates and thiosulfonates by reaction with (1) (eq 10). The reaction initially favors formation of the thiosulfinate, but on standing the reaction mixture changes to give more of the thiosulfonate. This reaction was later extended to the biologically important disulfide lipoic acid,22 where oxidation of methyl a-lipoate with (1) gave all four possible thiosulfinate isomers.

The oxidation of diazo compounds by singlet oxygen has provided an alternative route to carbonyl oxides and ozonides. This reaction can be carried out using (1) as a singlet oxygen source (eq 11).23 A carbonyl oxide, produced in this manner, has been used24 to epoxidize alkenes in low yield. However, the conditions of these reactions are such that some contribution of a direct reaction (see below) of (1) with the diazo compound cannot be ruled out.

Oxidation of acetone azine by (1) gives acetone.25 The reaction is believed to proceed via an electron transfer process. Triphenyl phosphite ozonide has also been used26 to convert several cyclopropenethiones to their oxygen analogs. The insertion of dioxygen into a silicon-silicon s-bond has been accomplished using several sources of singlet oxygen, including (1) (eq 12).27a This reaction was subsequently extended to oxadisilirane substrates, which give disilaozonides when treated with singlet oxygen.27b

The thermal generation of singlet oxygen from (1) can be accelerated by the presence of methanol and pyridine.28 A study of the mechanism of this effect indicates that it results from a successive displacement of phenoxy by methoxy groups in (1). The new phosphite ozonides then decompose at increased rates.

The Murray1a and Mendenhall1b articles contain some description of the chemistry of other phosphite ozonides. In general, this chemistry parallels that of (1) described here.

Use in Direct Bimolecular Transfer of Dioxygen.

In a number of cases the reaction of (1) with typical singlet oxygen substrates has been shown to proceed in a direct bimolecular manner without the release of singlet oxygen. In these cases, (1) is used below its decomposition temperature (usually -60 to -70 °C). Perhaps the most compelling evidence for this separate oxidation process comes from the reaction of (1) with cis- and trans-diethoxyethylene. This reaction gives3 the same distribution of dioxetanes from each of the stereoisomeric substrates (eq 13). The singlet oxygen reaction is known to give the dioxetanes in a stereospecific reaction with retention. Tetramethylethylene was shown to give the characteristic singlet oxygen ene reaction product when stored with (1) at temperatures well below the temperature at which singlet oxygen is released.3a,16 Relative rates of the reaction of (1) with typical singlet oxygen acceptors have been found to differ from those measured for singlet oxygen itself.1b When reacted with (1) at low temperature, dihydropyran gives16 two products in a ratio which differs greatly from that given in photosensitized oxidations (eq 14). Also, tricyclopropylethylene under similar low-temperature conditions gave products29 derived from an intermediate dioxetane, as opposed to the ene reaction products obtained when singlet oxygen is the oxidant.

Germacrene reacts directly with (1) to give30 (after reduction) an alcohol (eq 15) which is not formed in the singlet oxygen reaction. The latter reaction proceeds through two other modes of the ene reaction. Silyl enol ethers of a,b-unsaturated ketones are oxidized at low temperature by (1)31 to give alcohols with stereoselectivity different from that observed with m-Chloroperbenzoic Acid. An example is shown in eq 16. Several thioacetals have been oxidized by (1)32 to mixtures of sulfoxides and disulfoxides under conditions where the bimolecular reaction is likely. A pyrimidine derivative has been oxidized by (1) to the corresponding endoperoxide.33 The yields obtained were lower that those given by photosensitized oxidation.

Further evidence for the bimolecular reaction is available.16 An attempt has been made to present separately the two basic reaction modes of (1). However, some of the reactions presented in the section on the use of (1) as a singlet oxygen source were carried out under conditions such that the direct reaction may also have played a role.

Related Reagents.

Oxygen; Ozone-Silica Gel; Singlet Oxygen.


1. (a) Murray, R. W. In Singlet Oxygen, Wasserman, H. H.; Murray, R. W., Eds.; Academic: New York, 1979; p. 93. (b) Mendenhall, G. D. In Advances in Oxygenated Processes; JAI: Greenwich, CT, 1990; Vol. 2, p 203.
2. (a) Murray, R. W.; Kaplan, M. L. JACS 1968, 90, 4161. (b) Murray, R. W.; Kaplan, M. L. JACS 1968, 90, 537.
3. (a) Bartlett, P. D.; Mendenhall, G. D. JACS 1970, 92, 210. (b) Schaap, A. P.; Bartlett, P. D. JACS 1970, 92, 6055.
4. Knowles, W. S.; Thompson, Q. E. CI(L) 1959, 121.
5. Bartlett, P. D.; Chu, H.-K. JOC 1980, 45, 3000.
6. Wasserman, E.; Murray, R. W.; Kaplan, M. L.; Yager, W. A. JACS 1968, 90, 4160.
7. Khan, A. U.; Kasha, M. JACS 1970, 92, 3293.
8. Hurst, J. R.; McDonald, J. D.; Schuster, G. B. JACS 1982, 104, 2065.
9. Corey, E. J.; Taylor, W. C. JACS 1964, 86, 3880.
10. Mendenhall, G. D. Ph.D. Thesis, Harvard University, 1971.
11. Bartlett, P. D.; Mendenhall, G. D.; Durham, D. L. JOC 1980, 45, 4269.
12. Posner, G. H.; Weitzberg, M.; Nelson, W. M.; Murr, B. L.; Seliger, H. H. JACS 1987, 109, 278.
13. Bollyky, L. J. JACS 1970, 92, 3230.
14. Adam, W.; Lin, J.-C. CC 1972, 73.
15. Murray, R. W.; Lin, J. W.-P. ANY 1970, 171, 121.
16. Bartlett, P. D.; Mendenhall, G. D.; Schaap, A. P. ANY 1970, 171, 79.
17. Kopecky, K. R.; Scott, W. A.; Lockwood, P. A.; Mumford, C. CJC 1978, 56, 1114.
18. Foster, C. H.; Berchtold, G. A. JACS 1972, 94, 7939.
19. Matsuura, T.; Yoshimura, N.; Nishinaga, A.; Saito, I. TL 1969, 1669.
20. Bestmann, H. J.; Kisielowski, L.; Distler, W. AG(E) 1976, 15, 298.
21. Murray, R. W.; Smetana, R. D.; Block, E. TL 1971, 299.
22. Murray, R. W.; Stary, F. E.; Jindal, S. L. In Methods in Enzymology; Packer, L., Ed.; Academic: New York, 1984; Vol. 105, p 137.
23. Murray, R. W.; Higley, D. P. JACS 1974, 96, 3330.
24. Hinrichs, T. A.; Ramachandran, V.; Murray, R. W. JACS 1979, 101, 1282.
25. Landis, M. E.; Madoux, D. C. JACS 1979, 101, 5106.
26. Singh, S.; Ramamurthy, V. JOC 1985, 50, 3732.
27. (a) Ando, W.; Kako, M.; Akasaka, T.; Nagase, S.; Kawai, T.; Sato, T. TL 1989, 30, 6705. (b) Ando, W.; Kako, M.; Akasaka, T.; Nagase, S. OM 1993, 12, 1522.
28. Bartlett, P. D.; Lonzetta, C. M. JACS 1983, 105, 1984.
29. Ref. 1b, p 213.
30. Sam, T. W.; Sutherland, J. K. CC 1972, 424.
31. Iwata, C.; Takemoto, Y.; Nakamura, A.; Imanishi, T. TL 1985, 26, 3227.
32. Shereshovets, V. V.; Korotaeva, N. M.; Puzin, Yu. I.; Elichev, A. A.; Leplyanin, G. V.; Tolstikov, G. A. ZOR 1990, 26, 1259.
33. Gotthardt, H.; Schenk, K.-H. TL 1983, 24, 4669.

Robert W. Murray

University of Missouri-St. Louis, MO, USA



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