Oxidation with Dioxiranes

Overall Score3.5

Generality
Reagent Availability
Experimental User Friendliness
Criteria #4
Criteria #5

General Characteristics

Dimethyldioxirane (DMDO), prepared from acetone and Oxone®, is used frequently to oxidize alkenes to epoxides. Methyl(trifluoromethyl)dioxirane (TFDO) is about 600 times more reactive than DMDO.

Compared with mCPBA, the advantages of using dioxiranes are neutral reaction conditions, easy workup (since the byproduct is only acetone), and low cost of the reagents. However, dioxirane reagents are unstable and have to be prepared freshly for each experiment. These reagents require purification by vacuum distillation and somewhat special handling.

For certain substrates, direct hydroxylation of unactivated aliphatic C-H bonds is possible.

General References

Murray, R. W.; Jayaraman, R. J. Org. Chem. 1985, 50, 2847. DOI: 10.1021/jo00216a007
Adam, W.; Chan, Y.-Y.; Cremer, D.; Gauss, J.; Scheutzow, D.; Schindler, M. J. Org. Chem. 1987, 52, 2800. DOI: 10.1021/jo00389a029
Mello, R.; Fiorentino, M.; Sciacovelli, O.; Curci, R. J. Org. Chem. 1988, 53, 3890. DOI: 10.1021/jo00251a053
Mello, R.; Fiorentino, M.; Fusco, C.; Curci, R. J. Am. Chem. Soc. 1989, 111, 6749. DOI: 10.1021/ja00199a039
Adam, W.; Hadjiarapoglou, L.; Nestler, B. Tetrahedron Lett. 1990, 31, 331. doi:10.1016/S0040-4039(00)94547-7
Yang, D.; Wong, M.-K.; Yip. Y.-C. J. Org. Chem. 1995, 60, 3887. DOI: 10.1021/jo00117a046
Frohn, M.; Wang, Z.-X.; Shi, Y. J. Org. Chem. 1998, 63, 6425. DOI: 10.1021/jo980604+
Yang, D.; Wong, M.-K.; Wang, X. -C.; Tang, Y.-C. J. Am. Chem. Soc. 1998, 120, 6611. DOI: 10.1021/ja980916u
Ferraz, H. M. C.; Muzzi, R. M.; Vieira, T. O.; Viertler, H. Tetrahedron Lett. 2000, 41, 5021. doi:10.1016/S0040-4039(00)00769-3

Murray, R. W. Chem Rev. 1989, 89, 1187. DOI: 10.1021/cr00095a013
Curci, R.; Dinoi, A.; Rubino, M. F. Pure Appl. Chem. 1995, 67, 811. doi: 10.1351/pac199567050811
Curci, R.; D’Accolti, L.; Fusco, C. Acc. Chem. Res. 2006, 39, 1. DOI: 10.1021/ar050163y
Adam, W.; Saha-Moller, C. R.; Zhao, C.-G. Org. React. 2002, 61, 219.

Reaction Mechanism

Examples

The synthesis of morphine.^[1]

The synthesis of merrilactone.^[2]

An example of selective C-H oxygenation^[3]: Methine carbons are more reactive than methylene carbons.

The application to the synthesis of an extremely complex bryostatin analogue.^[4]

Experimental Procedure

Preparation of dimethyldioxirane.^[5a]

ADD EXPERIMENTAL LATER

Experimental Tips

*As is always the case with synthesis of peroxide compounds, the preparation of dioxiranes has a risk of explosion. A blast shield should be used.

*DMDO is a volatile peroxide and its handling requires extra caution. Use it only inside a fume hood.

*Touching and inhaling these strong oxidants must be avoided. Appropriate protective gloves should be worn.

References

[1] Trost, B. M.; Tang, W.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, 14785. DOI: 10.1021/ja054449+
[2] (a) Inoue, M.; Sato, T.; Hirama, M. J. Am. Chem. Soc. 2003, 125, 10772. DOI: 10.1021/ja036587+ (b) Inoue, M.; Sato, T.; Hirama, M. Angew. Chem. Int. Ed. 2006, 45, 4843. doi:10.1002/anie.200601358 (c) Inoue, M.; Lee, N.; Kasuya, S.; Sato, T.; Hirama, M.; Moriyama, M.; Fukuyama, Y. J. Org. Chem. 2007, 72, 3065. DOI: 10.1021/jo0700474
[3] (a) Bovicelli, P.; Lupattelli, P.; Mincione, E.; Prencipe, T.; Curci, R. J. Org. Chem. 1991, 57, 2182. DOI: 10.1021/jo00033a053 (b) Iida, T.; Yamaguchi, T.; Nakamori, R.; Hikosaka, M.; Mano, N.; Goto, J.; Nambara, T. J. Chem. Soc. Perkin Trans. 1 2001, 2229. DOI: 10.1039/B104938K
[4] Wender, P. A.; Hilinski, M. K.; Mayweb, A, V, W, Org. Lett. 2005, 7, 79. DOI: 10.1021/ol047859w
[5] (a) Li, Y.; Tang, P.; Chen, Y.; Yu, B. J. Org. Chem. 2008, 73, 4323. DOI: 10.1021/jo8003875 (b) Murray, R. W.; Singh, M. Org. Synth. Coll. Vol. 9, 288 (1988). [website]