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The '''Sharpless Epoxidation''' reaction is an [[enantiomer|enantioselective]] [[chemical reaction]] to prepare 2,3-epoxyalcohols from primary and secondary [[allyl alcohol|allylic alcohol]]s. Katsuki, T.; [[K. Barry Sharpless|Sharpless, K. B.]] ''[[J. Am. Chem. Soc.]]'' '''1980''', ''102'', 5974. ({{DOI|10.1021/ja00538a077}})Hill, J. G.; [[K. Barry Sharpless|Sharpless, K. B.]]; Exon, C. M.; Regenye, R. ''[[Org. Syn.]]'', Coll. Vol. 7, p.461 (1990); Vol. 63, p.66 (1985). ([http://www.orgsyn.org/orgsyn/prep.asp?prep=cv7p0461 Article])[[Image:Sharpless Asymmetric Epoxidation Scheme.png|center|400px|The Sharpless epoxidation]]

The stereochemistry of the resulting epoxide is determined by the diastereomer of the chiral tartrate diester (usually [[diethyl tartrate]] or [[diisopropyl tartrate]]) employed in the reaction. The oxidizing agent is [[tert-Butyl hydroperoxide|''tert''-butyl hydroperoxide]]. Enantioselectivity is achieved by a catalyst formed from [[Titanium isopropoxide|titanium tetra(isopropoxide)]] and diethyl tartrate. Only 5-10mol% of the catalyst in the presence of 3[[angstrom|]] [[molecular sieve]]s (3 MS) is necessary.Gao, Y.; Hanson, R. M.; Klunder,J. M.; Ko, S. Y.; Masamune, H.; [[K. Barry Sharpless|Sharpless, K. B.]] ''[[J. Am. Chem. Soc.]]'' '''1987''', ''109'', 5765-5780. ({{DOI|10.1021/ja00253a032}})

The Sharpless Epoxidation's success is due to five major reasons. First, epoxides can be easily converted into [[diol]]s, aminoalcohols or [[ether]]s, so format

ion of chiral epoxides is a very important step in the synthesis of natural products. Second, the Sharpless Epoxidation reacts with many primary and secondary allylic alcohols. Third, the products of the Sharpless Epoxidation frequently have [[enantiomeric excess]es above 90%. Fourth, the products of the Sharpless Epoxidation are predictable using the Sharpless Epoxidation model. Finally, the reactants for the Sharpless Epoxidation are commercially available and relatively cheap. Uetikon, C. F. ''[[Synthesis (Stuttgart)]]'' '''1986''', 88-116.

Several reviews have been published.Johnson, R. A.; [[K. Barry Sharpless|Sharpless, K. B.]] ''Comp. Org. Syn.'' '''1991''', ''7'', 389-436. (Review)Hft, E. ''Top. Curr. Chem.'' '''1993''', ''164'', 63-77. (Review)Katsuki, T.; Martin, V. S. ''Org. React.'' '''1996''', ''48'', 1-300. (Review)Pfenninger, A. ''Synthesis'' '''1986''', 89-116. (Review)

[[K. Barry Sharpless]] shared the 2001 [[Nobel prize in Chemistry]] for his workon asymmetric oxidations.The prize was shared with [[William S. Knowles]] and [[Ryji Noyori]].

==Catalyst Structure==The structure of the catalyst is still uncertain. No studies have been conductedthat definitively exclude other proposed catalysts. Regardless, all studies have concluded that the catalyst is a dimer of [Ti(tartrate)(OR)2][ Theputative catalyst was determined using X-ray structural determinations of modelcomplexes which have the necessary structural components to catalyze the Sharpl

ess Epoxidation.Finn, M. G.; [[K. Barry Sharpless|Sharpless, K. B.]] ''[[J.Am. Chem. Soc.]]'' '''1991''', ''113'', 113-126. ({{DOI|10.1021/ja00001a019}}).

[[File:Transition state.png|center|Transition state]]

==Selectivity==The chirality of the product of a sharpless epoxidation can be predicted using the following mnemonic. Draw the double bond of interest lying flat. Draw a rectangle that around the double bond is in same plane as the carbons of the double b

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ond. Towards the bottom right corner, draw the allylic alcohol. Place the othersubstituents in the appropiate 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 molcule. This model seems to be true independent of the substitution on the olefin. Selectivity decreases with larger R1, but increases with larger R2 and R3 (see introduction). Katsuki, T.; [[K. Barry Sharpless|Sharpless, K. B.]] ''[[J. Am. Chem. Soc.]]'' '''1980''', ''102'', 5974. ({{DOI|10.1021/ja00538a077}})

[[Image:mnenomic.png|center|400px|The Sharpless epoxidation]]

The product of allylic 1,2-diols is incorrectly predicted by this model. Takano, S.; Iwabuchi, Y.; Ogasawara, K. ''[[J. Am. Chem. Soc.]]'' '''1991''', ''113'', 2786-2787. ({{DOI|10.1021/ja00007a082}})[[File:Sharpless model violation.png|center|Sharpless model violation]]

==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.Kitano, Y.; Matsumoto, T.; Sato, F. ''[[Tetrahedron]]'' '''1988''', ''44'', 4073-4086.Martin, V.; Woodard, S.; Katsuki, T.; Yamada,Y.; Ikeda, M.; [[K. Barry Sharpless|Sharpless, K. B.]] ''[[J. Am. Chem. Soc.]]'' '''1981''', ''103'', 6237-6240. ({{DOI|10.1021/ja00410a053}})

[[File:Kinetic resolution .png|Kinetic resolution ]]==Synthetic Utility==The Sharpless Epoxidation is viable with a large range of primary and secondaryolefinic alcohols. Furthermore, with the exception noted above, a given dialkyltartrate will preferentially add to the same face independent of the substitution on the [[olefin]]. Katsuki, T.; [[K. Barry Sharpless|Sharpless, K. B.]] ''[[J. Am. Chem. Soc.]]'' '''1980''', ''102'', 5974. ({{DOI|10.1021/ja00538a077}})

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. Rossiter, B.; Katsuki, T.; [[K. Barry Sharpless|Sharpless, K. B.]] ''[[J. Am. Chem. Soc.

]]'' '''1981''', ''103'', 464-465. ({{DOI|10.1021/ja00392a038}})[[File:Utility.png|center|Utility]]

As one of the few, highly enantioselective reactions during its time, many manipulations of the of the 2,3-epoxyalcohols have been developed.[[K. Barry Sharpless|Sharpless, K. B.]]; Behrens, C. H.; Katsuki, T.; Lee, A. W. M.; Martin, V. S.; Takatani, M.; Viti, S.M.; Walker, F. J.; Woodard, S. S. ''[[Pure Appl. Chem.]]'' '''1983''', ''55'', 589.

The Sharpless Epoxidation has been used for the total synthesis of various [[carbohydrates]], [[terpenes]], [[leukotrienes]], [[pheromones]], and [[antibiotics]]. Uetikon, C. F. ''[[Synthesis (Stuttgart)]]'' '''1986''', 88-116.

==See also==* [[Asymmetric catalytic oxidation]]

==References==

==External links==*[http://www.chem.harvard.edu/groups/myers/handouts/16_Sharpless_Asymmetric_E.pdf Sharpless Asymmetric Epoxidation Reaction]

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{{DEFAULTSORT:Sharpless Epoxidation}}[[:Category:Organic redox reactions]][[:Category:Epoxides]][[:Category:Catalysis]][[:Category:Name reactions]]

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