Editing Sharpless epoxidation

{{Short description|Chemical reaction}}
{{Use dmy dates|date=April 2023}}
{{Reactionbox
| Name = Sharpless epoxidation
| Type = Ring forming reaction
| NamedAfter = [[Karl Barry Sharpless]]
| Section3 = {{Reactionbox Identifiers
 | OrganicChemistryNamed = sharpless-epoxidation
 | RSC_ontology_id = 0000141
}}
}}
The '''Sharpless epoxidation''' reaction is an [[enantiomer|enantioselective]] [[chemical reaction]] to prepare 2,3-epoxyalcohols from primary and secondary [[allyl alcohol|allylic alcohol]]s.  The [[oxidizing agent]] is [[tert-Butyl hydroperoxide|''tert''-butyl hydroperoxide]]. The method relies on a [[catalyst]] formed from [[Titanium isopropoxide|titanium tetra(isopropoxide)]] and [[diethyl tartrate]].<ref name = ChemRev>{{cite journal |doi=10.1021/cr040698p|title=In the Arena of Enantioselective Synthesis, Titanium Complexes Wear the Laurel Wreath|author=Diego J. Ramón and Miguel Yus|journal=Chem. Rev.|year=2006|volume=106|issue=6|pages=2126–2208|pmid=16771446}}</ref><ref>{{cite journal|author=Johnson, R. A.|author2=Sharpless, K. B.|author2-link=K. Barry Sharpless |journal=Compr. Org. Synth.|year=1991|volume=7|pages= 389–436|doi=10.1016/B978-0-08-052349-1.00196-7|title=Addition Reactions with Formation of Carbon–Oxygen Bonds: (ii) Asymmetric Methods of Epoxidation|isbn=978-0-08-052349-1}}</ref><ref>{{cite journal|author=Hüft, E. |journal=Top. Curr. Chem.|year=1993|volume=164|pages= 63–77|doi=10.1007/3-540-56252-4_25|title=Enantioselective epoxidation with peroxidic oxygen|series=Topics in Current Chemistry|isbn=978-3-540-56252-8}}</ref><ref>{{cite journal|title=Asymmetric Epoxidation of Allylic Alcohols: The Katsuki-Sharpless Epoxidation Reaction|doi=10.1002/0471264180.or048.01|author1=Katsuki, T. |author2=Martin, V. S. |journal=Org. React.|year=1996|volume=48|pages= 1–300|isbn=0471264180}}</ref><ref>{{cite journal|author=Pfenninger, A. |journal=Synthesis|year=1986|pages= 89–116|doi=10.1055/s-1986-31489|title=Asymmetric Epoxidation of Allylic Alcohols: The Sharpless Epoxidation|volume=1986|issue=2}}</ref>
[[File:Sharpless epoxidation DE.svg|center|400px|The Sharpless epoxidation]]

2,3-Epoxyalcohols can be converted into [[diol]]s, aminoalcohols, and [[ether]]s. The reactants for the Sharpless epoxidation are commercially available and relatively inexpensive.<ref name="Uetikon1986">{{cite journal|author=A. Pfenninger|journal=Synthesis |year=1986|pages= 88–116|doi=10.1055/s-1986-31489|title=Asymmetric Epoxidation of Allylic Alcohols: The Sharpless Epoxidation|volume=1986 |issue=2 }}</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]].

==Catalyst==
5–10&nbsp;mol% of the catalyst is typical.  The presence of [[angstrom|3Å]] [[molecular sieve]]s (3Å MS) is necessary.<ref>*{{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}}</ref> The structure of the catalyst is uncertain although it is thought to be a dimer of [{{Not a typo|Ti(tartrate)(OR){{sub|2}}}}].<ref>{{cite journal|author=Finn, M. G.|author2=Sharpless, K. B. |journal=J. Am. Chem. Soc.|year=1991|volume=113|pages= 113–126| doi=10.1021/ja00001a019|title=Mechanism of Asymmetric Epoxidation. 2. Catalyst Structure|issue=1 |bibcode=1991JAChS.113..113F }}</ref>

==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 R<sup>1</sup>, but increases with larger R<sup>2</sup> and R<sup>3</sup> (see introduction).<ref name = ChemRev/>

[[File:Mnemonic.png|center|400px|The Sharpless epoxidation]]

However, this method incorrectly predicts the product of allylic 1,2-diols.<ref>{{cite journal|author1=Takano, S. |author2=Iwabuchi, Y. |author3=Ogasawara, K. |journal=[[J. Am. Chem. Soc.]]|year=1991|volume=113|pages= 2786–2787| doi=10.1021/ja00007a082|title=Inversion of enantioselectivity in the kinetic resolution mode of the Katsuki-Sharpless asymmetric epoxidation reaction|issue=7|bibcode=1991JAChS.113.2786T }}</ref>
[[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.<ref>{{cite journal|author1=Kitano, Y. |author2=Matsumoto, T. |author3=Sato, F. |journal=[[Tetrahedron (journal)|Tetrahedron]]|year=1988|volume=44|pages= 4073–4086|doi=10.1016/S0040-4020(01)86657-6|title=A highly efficient kinetic resolution of γ- and β- trimethylsilyl secondary allylic alcohols by the sharpless asymmetric epoxidation|issue=13}}</ref><ref>{{cite journal|author=Martin, V.|author2=Woodard, S.|author3=Katsuki, T.|author4=Yamada, Y.|author5=Ikeda, M.|author6=Sharpless, K. B.|author6-link=K. Barry Sharpless |journal=[[J. Am. Chem. Soc.]]|year=1981|volume=103|pages= 6237–6240| doi=10.1021/ja00410a053|title=Kinetic resolution of racemic allylic alcohols by enantioselective epoxidation. A route to substances of absolute enantiomeric purity?|issue=20|bibcode=1981JAChS.103.6237M }}</ref>
[[File:Kinetic resolution.png|center|Kinetic resolution]]

==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]].<ref>{{cite journal|author=Rossiter, B.|author2=Katsuki, T.|author3=[[K. Barry Sharpless|Sharpless, K. B.]] |journal=[[J. Am. Chem. Soc.]]|year=1981|volume=103|pages= 464–465| doi=10.1021/ja00392a038|title=Asymmetric epoxidation provides shortest routes to four chiral epoxy alcohols which are key intermediates in syntheses of methymycin, erythromycin, leukotriene C-1, and disparlure|issue=2|bibcode=1981JAChS.103..464R }}</ref>

[[File:Utility.png|center|Utility]]

As one of the few highly enantioselective reactions during its time, many manipulations of the 2,3-epoxyalcohols have been developed.<ref>{{cite journal|author=[[K. Barry Sharpless|Sharpless, K. B.]]|author2=Behrens, C. H.|author3=Katsuki, T.|author4=Lee, A. W. M.|author5=Martin, V. S.|author6=Takatani, M.|author7=Viti, S.M.|author8=Walker, F. J.|author9=Woodard, S. S. |journal=[[Pure Appl. Chem.]]|year=1983|volume=55|pages= 589|doi=10.1351/pac198855040589|title=Stereo and regioselective openings of chiral 2,3-epoxy alcohols. Versatile routes to optically pure natural products and drugs. Unusual kinetic resolutions|issue=4|doi-access=free}}</ref>

The Sharpless epoxidation has been used for the total synthesis of various [[saccharides]], [[terpenes]], [[leukotrienes]], [[pheromones]], and [[antibiotic]]s.<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 group]]s.{{citation needed|date=December 2021}}  For specifically [[Darzens reaction|glycidic epoxides]], the Jørgensen-Córdova epoxidation avoids the need to reduce the carbonyl and then reoxidize, and has more efficient catalyst turnover.<ref>{{cite journal|url=https://www.organic-chemistry.org/Highlights/2010/05July.shtm|date=5 July 2010|first=Douglass&nbsp;F.|last=Taber|title=The Nicolaou synthesis of (+)-Hirsutellone B|journal=Organic Chemistry Highlights}}</ref>

==References of historic interest==
*{{cite journal|author=Katsuki, T.|author2=[[K. Barry Sharpless]] |journal=[[J. Am. Chem. Soc.]]|year=1980|volume=102|pages= 5974| doi=10.1021/ja00538a077|title=The first practical method for asymmetric epoxidation|issue=18|bibcode=1980JAChS.102.5974K }}
*{{cite journal|author=Gao, Y.|author2=Hanson, R. M.|author3=Klunder, J. M.|author4=Ko, S. Y.|author5=Masamune, H.|author6=Sharpless, K. B.|author6-link=K. Barry Sharpless |journal=[[J. Am. Chem. Soc.]]|year=1987|volume=109|pages= 5765–5780| doi=10.1021/ja00253a032|title=Catalytic asymmetric epoxidation and kinetic resolution: Modified procedures including in situ derivatization|issue=19|bibcode=1987JAChS.109.5765G }}

==See also==
* [[Asymmetric catalytic oxidation]]
* [[Juliá–Colonna epoxidation]]&nbsp;&mdash; for [[enone]]s
* [[Jacobsen epoxidation]]&nbsp;&mdash; for unfunctionalized alkenes

==References==
{{reflist}}

==External links==
*[https://web.archive.org/web/20060622054627/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:Epoxidation reactions]]
[[Category:Organic redox reactions]]
[[Category:Name reactions]]
[[Category:Epoxides]]
[[Category:Catalysis]]