| Sharpless epoxidation | |
|---|---|
| Named after | Karl Barry Sharpless |
| Reaction type | Ring forming reaction |
| Identifiers | |
| Organic Chemistry Portal | sharpless-epoxidation |
| RSC ontology ID | RXNO:0000141 |
TheSharpless epoxidation reaction is anenantioselectivechemical reaction to prepare 2,3-epoxyalcohols from primary and secondaryallylic alcohols. Theoxidizing agent istert-butyl hydroperoxide. The method relies on acatalyst formed fromtitanium tetra(isopropoxide) anddiethyl tartrate.[1][2][3][4][5]
2,3-Epoxyalcohols can be converted intodiols, aminoalcohols, andethers. The reactants for the Sharpless epoxidation are commercially available and relatively inexpensive.[6]K. Barry Sharpless published a paper on the reaction in 1980 and was awarded the2001 Nobel Prize in Chemistry for this and related work on asymmetricoxidations. The prize was shared withWilliam S. Knowles andRyōji Noyori.
5–10 mol% of the catalyst is typical. The presence of3Åmolecular sieves (3Å MS) is necessary.[7] The structure of the catalyst is uncertain although it is thought to be a dimer of [Ti(tartrate)(OR)2].[8]
Theepoxidation 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 followingmnemonic. A rectangle is drawn around the double bond in the same plane as the carbons of the double bond (thexy-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).[1]
However, this method incorrectly predicts the product of allylic 1,2-diols.[9]
The Sharpless epoxidation can also givekinetic resolution of a racemic mixture of secondary 2,3-epoxyalcohols. While the yield of a kinetic resolution process cannot be higher than 50%, theenantiomeric excess approaches 100% in some reactions.[10][11]
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 thealkene.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.[12]
As one of the few highly enantioselective reactions during its time, many manipulations of the 2,3-epoxyalcohols have been developed.[13]
The Sharpless epoxidation has been used for the total synthesis of varioussaccharides,terpenes,leukotrienes,pheromones, andantibiotics.[6]
The main drawback of this protocol is the necessity of the presence of anallylic alcohol. TheJacobsen epoxidation, an alternative method to enantioselectively oxidise alkenes, overcomes this issue and tolerates a wider array offunctional groups.[citation needed] For specificallyglycidic epoxides, the Jørgensen-Córdova epoxidation avoids the need to reduce the carbonyl and then reoxidize, and has more efficient catalyst turnover.[14]
