Osmium Tetroxide (OsO4)

• General Characteristics

In the presence of re-oxidants, a catalytic amount of osmium tetroxide (OsO₄) converts alkenes into cis-vicinal diols. Because of the mild reaction conditions and shortage of alternative methods for this transformation, expensive OsO₄ is still used frequently.

Acetone/water or t-BuOH/water mixed solvent systems are used often.

As the re-oxidant, N-methylmorpholine N-oxide (NMO), which is an easily handleable solid, is used most commonly (the Upjohn conditions). Trimethylamine oxide (Me₃NO), t-BuOOH (the Milas conditions), and OsCl₃-K₃Fe(CN)₆ are also known.

With sodium periodate (NaIO₄) as the re-oxidant, the diol products are oxidatively cleaved to give carbonyl compounds (the Lemieux-Johnson oxidation).

The presence of coordinating amines (such as pyridine) accelerates the reaction.

The addition of methanesulfonamide (MsNH₂) also has accelerating effect (presumably by promoting the hydrolysis of the osmate ester).

Ligands derived from quinine and quinidine are famously known to enable asymmetric dihydroxylation of alkenes (the Sharpless asymmetric dihydroxylation).

• General References

・Milas, N. A.; Sussman, S. J. Am. Chem. Soc. 1936, 58,1302. doi:10.1021/ja01298a065
・VanRheenen, V.; Kelly R. C.; Cha, D. Y. Terahedron Lett. 1976, 1973. doi:10.1016/S0040-4039(00)78093-2
・Sharpless, K. B.; Akashi, K. J. Am. Chem. Soc. 1976, 98, 1986. DOI: 10.1021/ja00423a067
・Lemieux-Johnson Oxidation: Pappo, R.; Allen, D. S., Jr.; Lemieux, R. U.; Johnson, W. S. J. Org .Chem. 1956, 21, 478. DOI:10.1021/jo01110a606

<reviews>
・Cha, J. K.; Kim, N.-S. Chem. Rev. 1995, 95, 1761. DOI: 10.1021/cr00038a003
・Eames, J.; Mitchell, H.; Nelson, A.; O’Brien, P.; Warren, S.; Wyatt, P. J. Chem. Soc. Perkin Trans. 1 1999, 1095. doi:10.1039/a900277d
・Francais, A.; Bedel, O.; Haudrechy, A. Tetrahedron 2008, 64, 2495. doi:10.1016/j.tet.2007.11.068

• Reaction Mechanism

The [3+2] cycloaddition of osmium tetroxide to an olefin gives an osmate ester intermediate. The intermediate needs to be hydrolyzed for catalytic turnover, so the reaction is generally carried out in an aqueous system. This hydrolysis step is regarded as rate determining.

• Examples

Using sodium periodate as the reoxidant, alkenes can be cleaved in one pot. 2,6-Lutidine is known to prevent side reactions.^[1]

Aminohydroxylation is possible by adding reagents such as Chloramine-T.^[2]

An example of intramolecular aminohydroxylation using sulfonyloxycarbamate.^[3]

An example of oxidative cyclization when the molecule has hydroxyl groups.^[4]

In the presence of phenylboronic acid, the reactivity improves dramatically and the diols can also be isolated as phenylboronic acid esters.^[5] This is an application to the synthesis of sordarin.^[6]

• Experimental Procedure

Dihydroxylation of cyclohexene.^[7]

• Experimental Tips

-Microencapsulated osmium tetroxide is convenient as it is nonvolatile and can be recycled by filtration. It is sold by Wako Pure Chemical Industries.

-Osmium tetroxide is volatile and highly toxic. Experiments should be conducted under ventilated hoods.

• References

[1] Yu, W.; Mei, Y.; Kang, Y.; Hua, Z.; Jin, Z. Org. Lett. 2004, 6, 3217. DOI: 10.1021/ol0400342
[2] Sharpless, K. B.; Chong, A. O.; O’Shima, K. J. Org. Chem. 1976, 41, 177. DOI: 10.1021/jo00863a052
[3] Donohoe, T. J.; Chughtai, M. J.; Klauber, D. J.; Griffin, D.; Campbell, A. D. J. Am. Chem. Soc. 2006, 128, 2514. DOI: 10.1021/ja057389g
[4] (a) Donohoe, T. J.; Harris, R. M.; Burrows, J.; Parker, J. J. Am. Chem. Soc. 2006, 128, 13704. DOI: 10.1021/ja0660148 (b) Donohoe, T. J.; Wheelhouse, K. M. P.; Lindsay-Scott,P. J.; Churchill, G. H.; Connolly, M. J.; Butterworth, S.; Glossop, P. A. Chem. Asian. J. 2009, 4, 1237. DOI: 10.1002/asia.200900168
[5] Iwasawa, N.; Kato, T.; Narasaka, K. Chem. Lett. 1988, 1721. doi:10.1246/cl.1988.1721
[6] Chiba, S.; Kitamura, M.; Narasaka, K. J. Am. Chem. Soc. 2006, 128, 6931. DOI: 10.1021/ja060408h
[7] VanRheenen, V.; Kelly R. C.; Cha, D. Y. Terahedron Lett. 1976, 1973. doi:10.1016/S0040-4039(00)78093-2
[8] (a) Nagayama, S.; Endo, M.; Kobayashi, S. J. Org. Chem. 1998, 63, 6094. DOI: 10.1021/jo981127y (b) Kobayashi, S.; Endo, M.; Nagayama, S. J. Am. Chem. Soc. 1999, 121, 11229. DOI: 10.1021/ja993099m

• Related Books

osmium reagent, oxidation of alkenes, oxidative cleavage of diols, synthesis of aldehydes and ketones, synthesis of diols