Sodium Periodate-Osmium Tetroxide1,2

NaIO4-OsO4
(NaIO4)

[7790-28-5]  · INaO4  · Sodium Periodate-Osmium Tetroxide  · (MW 213.89) (OsO4)

[20816-12-0]  · O4Os  · Sodium Periodate-Osmium Tetroxide  · (MW 254.20)

(oxidizing agent for oxidative cleavage of carbon-carbon double bonds3 to give aldehydes and ketones)

Physical Data: NaIO4: mp 300 °C (dec); specific gravity 3.865. OsO4: bp 130 °C; mp 40 °C; specific gravity 4.900 at 22 °C.

Solubility: NaIO4: sol H2O (14.4 g/100 mL H2O at 25 °C; 38.9 g/100 mL at 51.5 °C), H2SO4, HNO3, acetic acid; insol organic solvents. OsO4: sol alcohol, Et2O, benzene, CCl4, NH3, POCl3, H2O (25%).

Form Supplied in: NaIO4: colorless to white tetragonal, efflorescent crystals. OsO4: colorless to pale yellow crystals contained in ampules. Both reagents are readily available.

Handling, Storage, and Precautions: NaIO4: irritant; gloves and safety goggles should be worn when handling this oxidant; avoid inhalation of dust and avoid contact of oxidant with combustible matter. OsO4: acrid, chlorine-like odor; irritant; highly corrosive; causes burns to skin, eyes, and respiratory tract; gloves and safety goggles must be worn and this reagent must be handled in a well ventilated fume hood.

Introduction.

In 1956, Lemieux, Johnson, and co-workers first described3 the use of sodium periodate-osmium tetroxide for the direct oxidation of alkenic bonds to give carbonyl compounds. This reaction combines the hydroxylating properties of Osmium Tetroxide with the glycol cleavage capabilities of Sodium Periodate. Additionally, sodium periodate serves to regenerate osmium tetroxide during the reaction, thereby permitting the use of only catalytic amounts of the expensive and toxic osmium tetroxide. This oxidation complements the classical method of ozonization of double bonds followed by reductive cleavage. The reaction is usually carried out in a mixed aqueous solvent system such as aqueous dioxane, aqueous THF, aqueous acetone, or aqueous DME. Water is required in this reaction for the hydrolysis of the intermediate osmate ester. In reactions where the carbonyl products are prone to self-condensation, the use of the ether-water system is found to be highly satisfactory.

Oxidative Cleavage of Double Bonds to Give Carbonyl Compounds.

The oxidation of acyclic alkenes and stilbene in aqueous 1,4-dioxane using sodium periodate in the presence of catalytic amounts of osmium tetroxide (NaIO4-cat. OsO4) yields the corresponding aldehydes in good yields (eqs 1 and 2).3,4 In contrast, the oxidation of cyclohexene under the same conditions gives only a low yield of adipaldehyde. The low yield is attributed to the tendency of adipaldehyde to undergo self-condensation. The use of an ether-water system for the oxidation circumvents this problem. Under the modified conditions, the oxidation of cyclohexene gives a good yield of adipaldehyde (eq 3).3 Similarly, cyclopentene is oxidized to afford glutaraldehyde in good yield. 1-Methylcyclohexene, however, is oxidized very slowly under the optimum conditions found for cyclohexene; only a small amount of an uncharacterized carbonyl compound is obtained. Nevertheless, this outcome suggests that NaIO4-cat. OsO4 can be employed for the selective cleavage of unhindered double bonds in the presence of hindered ones. This type of selective oxidation is effectively applied to the cleavage of a vinyl group in the presence of a more hindered alkenic bond in the etorphine ring system (eq 4).5

Alkenic compounds are rapidly and efficiently cleaved to carbonyl compounds using NaIO4 in the presence of polymer-supported OsO4 (P-OsO4) (eqs 5 and 6).6 Cyclohexene is oxidized to give a fairly good yield of adipaldehyde (eq 7). This provides a useful alternative to oxidation in the ether-water system3 alluded to earlier. a,b-Unsaturated carbonyl compounds are oxidized at the double bond to give aldehydes in good yields (eq 8). A notable feature of this method6 is that a particular oxidation can be easily repeated, at least 10 times, by simply adding new portions of substrate and sodium periodate.

The double bond in alkyl, cycloalkylmethyl, and arylmethyl allyl ethers can be oxidatively cleaved using NaIO4-cat. OsO4. The oxidation of (1) in aqueous dioxane containing trace amounts of acetic acid affords a good yield of the benzyloxy aldehyde (eq 9).7 On the other hand, oxidation of similar systems8 in aqueous dioxane results in only low yields of aldehydes. Higher yields are obtained when the oxidation is carried out using the ether-water system (eq 10).

Allylic alcohols are oxidized using NaIO4-cat. OsO4, with concomitant loss of two carbon units, to furnish good yields of the expected aldehyde (eq 11).9 The double bond in hydroxy alkenes, such as in (R)-(+)-citronellol, is selectively oxidized to give the corresponding hydroxy aldehydes which, upon subsequent Wittig alkenation, give the a,b-unsaturated esters (eq 12).10

The oxidation of g,d-unsaturated carbonyl substrates using NaIO4-cat. OsO4 is a practical method for the preparation of synthetically useful 1,4-dicarbonyl compounds.11 For example, oxidation of the double bond of the allyl moiety in (2) yields the aldehyde in good yield (eq 13).11a Subsequent base-catalyzed aldol condensation of the keto aldehyde furnishes the spirocyclopentenone derivative, albeit in low yield. Such a protocol has been employed for the preparation of key cyclopentenone intermediates used in natural products synthesis, e.g. in the syntheses of phytuberin (eq 14),12 aphidicolin (eq 15),13 and bakkenolide (eq 16).14

The 1-methylvinyl group can be used as a latent acetyl unit in synthesis. This is exemplified in the synthesis of a key intermediate required for the construction of the polyether antibiotic carbamonensin (eq 17).15 The acetyl group is subsequently utilized for the stereospecific installation of the acetate moiety via Baeyer-Villiger oxidation. Double bonds present in polyoxygenated systems have also been efficiently oxidized to the aldehydes in high yields (eq 18).9

The reaction conditions used for the NaIO4-cat. OsO4 oxidation are mild and this permits the oxidation of double bonds in the presence of acid or base labile groups such as the ester (eq 19),11b carbamate, acetal (eq 20),16 silyl ether (eq 21),17 and carbonate (eq 22)18 functions.

Cyclobutanones have been prepared from alkylidene- or arylidenecyclobutanes via the NaIO4-cat. OsO4 oxidation.19 The oxidation of benzylidenecyclobutane with NaIO4-cat. OsO4 gives cyclobutanone, albeit in low yields (17%).19a This outcome, however, is better than the ozonolysis method, which does not yield any cyclobutanone. The NaIO4-cat. OsO4 oxidation of 3-methylenecyclobutanecarboxylic acid is more successful and a good yield of 3-oxocyclobutanecarboxylic acid is obtained (eq 23).19b This protocol for the preparation of cyclobutanone from methylenecyclobutane has been used in natural product synthesis (eq 24).20

Alkenic bonds in heterocyclic molecules have also been oxidatively cleaved using NaIO4-cat. OsO4. Oxidation of the methylenecyclobutane moiety in the 2-quinolone derivative affords a good yield of the cyclobutanone derivative (eq 25).21 1-Substituted 2-nitroimidazole-5-carbaldehydes are prepared in useful yields by the action of NaIO4-cat. OsO4 on 5-vinylimidazole precursors (eq 26).22 This method is better than the two-step procedure, namely, Potassium Permanganate hydroxylation followed by NaIO4 oxidation of the 1,2-diol, which gives a lower yield of the product. Previous attempts to prepare 2-nitroimidazole-5-carbaldehydes such as by the ozonolysis of 5-vinylimidazoles and by the direct oxidation of 5-methyl-2-nitroimidazoles with CAN or SeO2 were unsuccessful. NaIO4-cat. OsO4 is effective for the oxidation of double bonds in 2-azetidinone derivatives to give a good yield of the co rresponding aldehydes (eq 27).23

Other Applications.

NaIO4-cat. OsO4 is a mild oxidizing agent and does not oxidize aryl groups. However, pyrene has been oxidized using NaIO4-cat. OsO4 to afford two major products arising from oxidation at the 4,5-double bond (eq 28).24 The use of OsO4-H2O2 gives only a low yield of the 4,5-quinone and most of the starting material is recovered. RuO2-NaIO4 oxidation is less specific and a mixture of products, resulting from attack at positions other than the 4,5-double bond, is obtained.


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2. (a) Schroder, M. CRV 1980, 80, 187. (b) Singh, H. S. Organic Synthesis By Oxidation With Metal Compounds; Mijs, W. J.; de Jonge, C. R. H. I., Eds.; Plenum: New York, 1986; p 633.
3. Pappo, R.; Allen, D. S., Jr.; Lemieux, R. U.; Johnson, W. S. JOC 1956, 21, 478.
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12. Kido, F.; Kitahara, H.; Yoshikoshi, A. JOC 1986, 51, 1478.
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16. Jurczak, J.; Pikul, S. T 1988, 44, 4569.
17. Gillard, F.; Heissler, D.; Riehl, J.-J. JCS(P1) 1988, 2291.
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19. (a) Graham, S. H.; Williams, A. J. S. JCS(C) 1966, 655. (b) Caserio, F. F., Jr.; Roberts, J. D. JACS 1958, 80, 5837.
20. Iwata, C.; Takemoto, Y.; Doi, M.; Imanishi, T. JOC 1988, 53, 1623.
21. Chiba, T.; Kato, T.; Yoshida, A.; Moroi, R.; Shimomura, N.; Momose, Y.; Naito, T.; Kaneko, C. CPB 1984, 32, 4707.
22. Cavalleri, B.; Ballotta, R.; Lancini, G. C. JHC 1972, 9, 979.
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24. Oberender, F. G.; Dixon, J. A. JOC 1959, 24, 1226.

Andrew G. Wee & Baosheng Liu

University of Regina, Saskatchewan, Canada



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