Sharpless epoxidation

Catalyst

5–10 mol% of the catalyst is typical. The presence of 3Å molecular sieves (3Å MS) is necessary.*{{cite journal|author1=Hill, J. G. |author2=Sharpless, K. B. |author3=Exon, C. M. |author4=Regenye, R. |journal=Org. Synth.|volume=63|pages=66|year=1985|doi=10.15227/orgsyn.063.0066| title=Enantioselective Epoxidation of Allylic Alcohols: (2s,3s)-3-propyloxiranemethanol}} The structure of the catalyst is uncertain although it is thought to be a dimer of [Ti(tartrate)(OR)].

Selectivity

The epoxidation of allylic alcohols is a well-utilized conversion in fine chemical synthesis. The chirality of the product of a Sharpless epoxidation is sometimes predicted with the following mnemonic. A rectangle is drawn around the double bond in the same plane as the carbons of the double bond (the xy-plane), with the allylic alcohol in the bottom right corner and the other substituents in their appropriate corners. In this orientation, the (−) diester tartrate preferentially interacts with the top half of the molecule, and the (+) diester tartrate preferentially interacts with the bottom half of the molecule. This model seems to be valid despite substitution on the olefin. Selectivity decreases with larger R1, but increases with larger R2 and R3 (see introduction).

However, this method incorrectly predicts the product of allylic 1,2-diols.

Kinetic resolution

The Sharpless epoxidation can also give kinetic resolution of a racemic mixture of secondary 2,3-epoxyalcohols. While the yield of a kinetic resolution process cannot be higher than 50%, the enantiomeric excess approaches 100% in some reactions.

Synthetic utility

The Sharpless epoxidation is viable with a large range of primary and secondary alkenic alcohols. Furthermore, with the exception noted above, a given dialkyl tartrate will preferentially add to the same face independent of the substitution on the alkene.To demonstrate the synthetic utility of the Sharpless epoxidation, the Sharpless group created synthetic intermediates of various natural products: methymycin, erythromycin, leukotriene C-1, and (+)-disparlure.

As one of the few highly enantioselective reactions during its time, many manipulations of the 2,3-epoxyalcohols have been developed.

The Sharpless epoxidation has been used for the total synthesis of various saccharides, terpenes, leukotrienes, pheromones, and antibiotics.

The main drawback of this protocol is the necessity of the presence of an allylic alcohol. The Jacobsen epoxidation, an alternative method to enantioselectively oxidise alkenes, overcomes this issue and tolerates a wider array of functional groups. For specifically glycidic epoxides, the Jørgensen-Córdova epoxidation avoids the need to reduce the carbonyl and then reoxidize, and has more efficient catalyst turnover.

References of historic interest

References

References

1. Diego J. Ramón and Miguel Yus. (2006). "In the Arena of Enantioselective Synthesis, Titanium Complexes Wear the Laurel Wreath". Chem. Rev..
2. Johnson, R. A.. (1991). "Addition Reactions with Formation of Carbon–Oxygen Bonds: (ii) Asymmetric Methods of Epoxidation". Compr. Org. Synth..
3. Hüft, E.. (1993). "Enantioselective epoxidation with peroxidic oxygen". Top. Curr. Chem..
4. (1996). "Asymmetric Epoxidation of Allylic Alcohols: The Katsuki-Sharpless Epoxidation Reaction". Org. React..
5. Pfenninger, A.. (1986). "Asymmetric Epoxidation of Allylic Alcohols: The Sharpless Epoxidation". Synthesis.
6. A. Pfenninger. (1986). "Asymmetric Epoxidation of Allylic Alcohols: The Sharpless Epoxidation". Synthesis.
7. Finn, M. G.. (1991). "Mechanism of Asymmetric Epoxidation. 2. Catalyst Structure". J. Am. Chem. Soc..
8. (1991). "Inversion of enantioselectivity in the kinetic resolution mode of the Katsuki-Sharpless asymmetric epoxidation reaction". [[J. Am. Chem. Soc.]].
9. (1988). "A highly efficient kinetic resolution of γ- and β- trimethylsilyl secondary allylic alcohols by the sharpless asymmetric epoxidation". [[Tetrahedron (journal).
10. Martin, V.. (1981). "Kinetic resolution of racemic allylic alcohols by enantioselective epoxidation. A route to substances of absolute enantiomeric purity?". [[J. Am. Chem. Soc.]].
11. Rossiter, B.. (1981). "Asymmetric epoxidation provides shortest routes to four chiral epoxy alcohols which are key intermediates in syntheses of methymycin, erythromycin, leukotriene C-1, and disparlure". [[J. Am. Chem. Soc.]].
12. [[K. Barry Sharpless. (1983). "Stereo and regioselective openings of chiral 2,3-epoxy alcohols. Versatile routes to optically pure natural products and drugs. Unusual kinetic resolutions". [[Pure Appl. Chem.]].
13. Taber, Douglass F.. (5 July 2010). "The Nicolaou synthesis of (+)-Hirsutellone B". Organic Chemistry Highlights.