Sharpless epoxidation
Template:Short description Template:Use dmy dates Template:Reactionbox The Sharpless epoxidation reaction is an enantioselective chemical reaction to prepare 2,3-epoxyalcohols from primary and secondary allylic alcohols. The oxidizing agent is tert-butyl hydroperoxide. The method relies on a catalyst formed from titanium tetra(isopropoxide) and diethyl tartrate.<ref name = ChemRev>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>
2,3-Epoxyalcohols can be converted into diols, aminoalcohols, and ethers. The reactants for the Sharpless epoxidation are commercially available and relatively inexpensive.<ref name="Uetikon1986">Template:Cite journal</ref> K. Barry Sharpless published a paper on the reaction in 1980 and was awarded the 2001 Nobel Prize in Chemistry for this and related work on asymmetric oxidations. The prize was shared with William S. Knowles and Ryōji Noyori.
CatalystEdit
5–10 mol% of the catalyst is typical. The presence of 3Å molecular sieves (3Å MS) is necessary.<ref>*Template:Cite journal</ref> The structure of the catalyst is uncertain although it is thought to be a dimer of [[[:Template:Not a typo]]].<ref>Template:Cite journal</ref>
SelectivityEdit
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).<ref name = ChemRev/>
However, this method incorrectly predicts the product of allylic 1,2-diols.<ref>Template:Cite journal</ref>
Kinetic resolutionEdit
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.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>
Synthetic utilityEdit
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.<ref>Template:Cite journal</ref>
As one of the few highly enantioselective reactions during its time, many manipulations of the 2,3-epoxyalcohols have been developed.<ref>Template:Cite journal</ref>
The Sharpless epoxidation has been used for the total synthesis of various saccharides, terpenes, leukotrienes, pheromones, and antibiotics.<ref name="Uetikon1986" />
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.Template:Citation needed For specifically glycidic epoxides, the Jørgensen-Córdova epoxidation avoids the need to reduce the carbonyl and then reoxidize, and has more efficient catalyst turnover.<ref>Template:Cite journal</ref>
References of historic interestEdit
See alsoEdit
- Asymmetric catalytic oxidation
- Juliá–Colonna epoxidation — for enones
- Jacobsen epoxidation — for unfunctionalized alkenes