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. Compound 8 and 9 can be used as the key intermediates for synthesis of the polyhydroxygibberellins. Sharpless epoxidation organic chemistry video clutch prep. The high enantioselectivity of this reaction is attributed to precoordination of the alcohol functional group to the titanium center. Catalytic asymmetric epoxidation of alkenes has been the focus of many research efforts over the past two decades, the best known methods probably being those developed by sharpless 1 and jacobsenkatsuki. How do you select for one enantiomer over another side note. Pdf an overview of the synthesis and applications of chiral 2,3epoxy alcohols containing unsaturated chains is presented. The processes for the selective oxidation of olefins have long been among the most useful tools for day. The sharpless epoxidation reaction is an enantioselective chemical reaction to prepare 2,3epoxyalcohols from primary and secondary allylic alcohols. In 1980, sharpless and katsuki discovered a system for the asymmetric epoxidation of primary allylic alcohols that utilizes tiopr. Efficient polymersupported sharpless alkene epoxidation. Asymmetric dihydroxylation of olefins is a core transformation in organic chemistry and its synselective version is commonly catalysed by toxic osmium catalysts.
Catalytic asymmetric epoxidation of allylic alcohols. Myers sharpless asymmetric dihydroxylation reaction chem 115. Myers sharpless asymmetric epoxidation reaction chem 115. The literature value is around 90%, but i only got 50%. The first asymmetric epoxidation of a tertiary allylic alcohol by the katsuki sharpless reaction has been demonstrated using e2,5dihydroxy2,5 dimethyl3hexene as a tertiary allylic alcohol. The first successful polymersupported sharplesstype.
The present invention provides a method for efficiently proceeding sharpless asymmetric epoxidation without adding molecular sieves. The sharpless epoxidation reaction is an enantioselective chemical reaction to prepare 2. The katsukisharpless epoxidation reaction is one of the most recognized chiral catalytic reactions, allowing for chiral epoxides to be used as starting materials for a series of synthetic pathways. Quilez del moral, alvaro perez, maria del mar herrador, alejandro f. Sharpless asymmetric epoxidation mcmaster university. All structured data from the file and property namespaces is available under the creative commons cc0 license. The oxidant for the epoxidation is tert butyl hydroperoxide. This file is licensed under the creative commons attributionshare alike 4. Epoxidation of unsaturated hydrocarbons is an important area of academic and industrial research as epoxides give direct access to a variety of products 68. In 1980, katsuki and sharpless reported the asymmetric epoxidation of substituted allylic alcohols by using chiral diethyl tartrate, titanium tetraisopropoxide and tertbutyl hydroperoxide as oxidant.
Ppt sharpless asymmetric epoxidation powerpoint presentation free to download id. Reaction tolerates acetals, alkynes, alcohols, aldehydes, amides, azides, carbamates, epoxides, esters, ethers. The aim of this work was to synthesise a polymer supported ligand for the sharpless asymmetric epoxidation, which could be recovered with ease and then reused without significant reduction in the enantiomeric excess in the epoxyalcohol product. Chemistry, manufacture and applications of natural rubber, 2014. Polymersupported metal complex alkene epoxidation catalysts. This process is experimental and the keywords may be updated as the learning algorithm improves.
The sharpless asymmetric epoxidation converts alkenes into chirally active epoxides innumerable syntheses published that use the sae chiral epoxides easily converted into. The katsuki sharpless epoxidation reaction is one of the most recognized chiral catalytic reactions, allowing for chiral epoxides to be used as starting materials for a series of synthetic pathways. This is the case with manganesesalen catalyzed epoxidation of cinnamate esters with. Sharpless was born april 28, 1941 in philadelphia, pa.
This page was last edited on 26 november 2016, at 01. Jun 25, 2009 enantioselective epoxidation of allylic alcohols using tbutyl peroxide, titanium tetra isopropoxide, and optically pure diethyl tartrate. Asymmetric epoxidation of allylic alcohol 535 derived from. Abstract the double asymmetric katsukisharpless epoxidation of a conjugated diallyl alcohol affords excellent enantioselectivity 97 % ee, the product being isolated as the stable p. Substrate scope of ketone 1 o o o o o o 1 ph ph o 85% yield 98% ee c6h c6h 89%. In same year, an enantioselective catalytic hydroxylation of double bonds with noxideos0 4 chiral base has been developed in sharplesss laboratory. An epoxide is a cyclic ether with a threeatom ring. Jan 10, 2019 the katsukisharpless epoxidation reaction is one of the most recognized chiral catalytic reactions, allowing for chiral epoxides to be used as starting materials for a series of synthetic pathways. Epoxidation condensation approaches darzens condensation sulfur ylides with organic peroxides peroxy acids peroxy iminic acids dioxiranes dmdo enantioselective versions metalcatalyzed approaches voacac 2 sharpless ae metal oxos mto fe, pt and mnbased. Welch foundation conferences on chemical research xxvii stereospecificity in chemistry and biochemistry, november 79, 1983, houston, tx. Barry sharpless, an mit chemistry professor for 17 years until he joined scripps research institute in 1990, was chosen october 10 to share the 2001 nobel prize in chemistry with two other researchers.
A new target for highly stereoselective katsukisharpless. Turnover is achieved by reoxidation with stoichiometric oxidants. Second, the sharpless epoxidation reacts with many primary and secondary allylic alcohols. Ohoh roh r r r r oh 90% ee r scope of the katsukisharpless asymmetric epoxidation oh 8695% ee r 9295% functional group compatibility. Katsukisharpless asymmetric epoxidation request pdf. Enantioselective synthesis of epoxides via sharpless.
Consequently, epoxidations by peracids always have synstereoselectivity, and seldom give structural rearrangement. In this example, a stoichiometric amount of titanium and dipt was necessary for high conversion. Notably, this reaction exhibits high levels of enantioselectivity usually. Given the commercial availability and low cost of the reagents, the large scope, the high enantioselectivity of the reaction, and the. Guidelines for asymmetric epoxidation prepared by o. Peptide 9b appears to operate via a hydroxyldirecting mechanism, analogous to sharpless asymmetric epoxidation and with comparable selectivity. Apr 28, 2015 this reaction adds a 3membered cycle ether epoxide functional group to an alkene using reagents called peroxy acids. Epoxidation with in situ prepared manganese based homogeneous catalysts 69 stepwise mechanism route b operates, rotation around the former double bond in 6 can cause isomerization during reaction leading to the obtainment of transepoxides from cisolefins. Sharpless, discovery of the titaniumcatalyzed asymmetric epoxidationa personal account. The epoxidation reaction is believed to occur in a single step with a transition state incorporating all of the bonding events shown in the equation.
By changing the catalyst it is now possible to convert simple alkenes to the corresponding epoxide with highasymmetric induction. Evaluation of the katsukisharpless epoxidation precatalysts by esiftms, cid, and irmpd spectroscopy. In catalytic asymmetric synthesis, 2nd ed ojima, i. The sharpless epoxidation of molybdenum peroxide and tungsten peroxide. Efficient polymersupported sharpless alkene epoxidation catalyst. The complete understanding of this reaction mechanism depends on the identification and description of species formed from tiiv alkoxides and alkyl tartrates precatalysts. When drawn in this manner the stereochemistry can be predicted. They are produced on a large scale for many applications. Peptide 12d, provides unprecedented selectivity for a catalyst for the internal olefin of farnesol, with substantial siteselectivity, but modest enantioselectivity. Pdf synthetic applications of chiral unsaturated epoxy alcohols. Downloaded by univ of montana on september 18, 2009. Asymmetric synthesis of azidotetrahydropyranols via sharpless. The sharpless asymmetric epoxidation only works with allylic alcohols, as illustrated by the conversion of 156 to 157 or 158 to 159.
Download fulltext pdf download fulltext pdf asymmetric synthesis of azidotetrahydropyranols via sharpless epoxidation article pdf available in archive for organic chemistry 20023 march. This ring approximates an equilateral triangle, which makes it strained, and hence highly reactive, more so than other ethers. The stereochemistry of the resulting epoxide is determined by the diastereomer of diethyl tartrate or diisopropyl tartrate employed in the reaction. Silanestabilized au nps were prepared by reduction of haucl 4 in a biphasic system using. Sharpless asymmetric dihydroxylation sharpless ad chem. In this example, excess tbhp was quenched with triethylphosphite instead of feii sulfate. Epoxidation of an asymmetrical alkene is usually a nonstereospecfic process, yielding a racemic mixture of enantiomers. He graduated from friends central school in 1959, and continued his studies at dartmouth college, earning an a. Catalysis today 57 2000 87104 polymersupported metal complex alkene epoxidation catalysts d. Asymmetric sharpless epoxidation of divinylcarbinol. Meo2cme2, pocl3 ochph 2 sph o o paynerearrangement. Promising results were found for the catalytic epoxidation of alkenes with gold nps 5,6972. Jp2012201651a sharpless asymmetric epoxidation reaction.
In independent work, katsuki and jacobsen showed that asymmetric epoxidation occurs using manganesesalen catalysts in the presence. Examples of the sharpless asymmetric epoxidation reaction in industry. Oct 24, 2006 asymmetric epoxidation of methyl gibberellate by the modified sharpless reagent in the various temperature is described. Lets remember, epoxidation is oxidation reaction of alkenes where cyclic ethers are obtained in which both carbons of double bond become bonded to the same oxygen atom. Evaluation of the katsukisharpless epoxidation precatalysts. The sharpless lab was the first academic chemistry group with robotics, and the lesson from the combinatorial numbers game was the primacy of reliability. Combinatorial evolution of site and enantioselective.
These epoxides are highly strained, so they can react in very useful ring. Ligands such as pyridine accelerate the osmylation of ole. Removal and recovery of the polymer catalyst is a simple filtration at the end of reactions. Karl barry sharpless born april 28, 1941 is an american chemist and nobel laureate known for his work on stereoselective reactions and click chemistry. The first asymmetric epoxidation of a tertiary allylic alcohol by the katsukisharpless reaction has been demonstrated using e2,5dihydroxy2,5 dimethyl3hexene as a tertiary allylic alcohol. Allylic alcohol salen complex cinchona alkaloid cyclohexene oxide asymmetric epoxidation these keywords were added by machine and not by the authors. Sharpless epoxidation an overview sciencedirect topics. The sharpless epoxidation of molybdenum peroxide and tungsten. The first practical method for asymmetric epoxidation. Searching for new reactivity nobel lecture sharpless. Myers sharpless asymmetric epoxidation reaction chem 115 a further example of anomalous stereochemistry in ae of an allylic diol no reaction with dipt. Enantioselective synthesis of simple epoxides can be achieved by sharpless epoxidation of alkenylsilanols followed by protodesilylation of the chiral epoxysilanols. Pdf efficient polymersupported sharpless alkene epoxidation.
Notably, this reaction exhibits high levels of enantioselectivity usually 90% ee. Converts primary and secondary allylic alcohols into 2,3 epoxyalcohols. The approach has been applied to the synthesis of frontalin. Epoxidation is the chemical reaction which converts the carboncarbon double bond into oxiranes epoxides, using a variety of reagents including air oxidation, hypochlorous acid, hydrogen peroxide, and organic peracid fettes, 1964. The asymmetric induction is achieved by adding an enantiomerically enriched tartrate derivative. Pdf asymmetric synthesis of azidotetrahydropyranols via.
Epoxidation, dihydroxylation, and the utility of epoxides and diols ready outline. Apr 15, 2004 in 1980, sharpless and katsuki discovered a system for the asymmetric epoxidation of primary allylic alcohols that utilizes tiopr. Asymmetric epoxidation of methyl gibberellate by the modified. The sharpless epoxidation or sae, sharpless asymmetric epoxidation is an enantioselective epoxidation of allylic alcohols. Recoverable ligands for the sharpless asymmetric epoxidation. I was hoping some of you chemistry masters could help a girl out. Barry sharpless figured this puzzle out in 1980, receiving a nobel prize in 2001. First, epoxides can be easily converted into diols, aminoalcohols or ethers, so formation of chiral epoxides is a very important step in the synthesis of natural products. The sharpless epoxidation allows the enantioselective epoxidation of prochiral allylic alcohols. Very important topic from paper and synthesis point of view. Wang ge university of science and technology beijing, beijing 83, china.
The first successful polymersupported sharplesstype epoxidation catalyst has been developed. An allyl alcohol compound, a catalytic amount of titanium tetraalkoxide, a catalytic amount of an optically active tartaric acid ester, and an oxidizing agent are mixed in a solvent using a flow reactor flow reactor. Nov 23, 2016 sharpless epoxidation the sharpless epoxidation reaction is an enantioselective chemical reaction to prepare 2,3 epoxyalcohols from primary and secondary allylic alcohols the stereochemistry of the resulting epoxide is determined by the diastereomer of the chiral tartrate diester used in the reaction the oxidizing agent is tert. Analysis of biosynthetic pathways reveals that functional group selectivity in enzymatic reactions is a persistent issue. The journal of physical chemistry a 2019, 123 5, 10221029. Improved method for epoxidation of ethylenic alcohols is provided employing catalytic amounts of a titaniumglycol catalyst and a peroxide under mild conditions which provide for the continuous maintenance of an anhydrous medium during catalyst formation and during the course of the reaction. Barry sharpless scripps won the noble prize in chemistry in 2001 for the development of catalytic asymmetric oxidation reactions such as this dihydroxylation and the sharplesskatsuki epoxidation. Barry sharpless and coworkers now at scripps research institute and is commonly referred to as the sharpless asymmetric epoxidation. Files are available under licenses specified on their description page. Asymmetric epoxidation of allylic alcoholsa 3lidietnyl tartrcte jnncturol 1. Molybdenumcatalyzed asymmetric anti dihydroxylation of.
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