On the mechanism of the organocatalytic asymmetric epoxidation of. 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. The oxidant for the epoxidation is tert butyl hydroperoxide. According to the criegee mechanism, 1,3dipolar cycloaddition gives a 1,2,3trioxolane product that rearranges to a 1,2,4 trioxolane. The journal of organic chemistry 2005, 70 5, 17281731. Consequently, epoxidations by peracids always have synstereoselectivity, and seldom give structural rearrangement. The products of the sharpless epoxidation frequently have enantiomeric excesses above 90%. Different reagent systems, including the sharpless epoxidation of allylic alcohols using tartaric acid, have been used to affect this reaction stereospecifically. By adding a chiral ligand to the titanium catalyst the reaction becomes asymmetric. Discovery by sharpless of the asymmetric ti tartrate epoxidation of allylic alcohols. Barry sharpless figured this puzzle out in 1980, receiving a nobel prize in 2001.
The sharpless epoxidation reacts with many primary and secondary allylic alcohols. The mechanism of nucleophilic epoxidation begins with conjugate addition of the peroxide or other onucleophilic species to the enone. On the basis of the newly proposed hypothesis on the mechanism of asymmetric induction, highly efficient salenmanganeseiii complex 3 was constructed as a. Often abbreviated mcpba, it is a stable crystalline solid. The jacobsen epoxidation allows the enantioselective formation of epoxides from various cissubstituted olefins by using a chiral mnsalen catalyst and a stoichiometric oxidant such as bleach. Sharpless asymmetric epoxidation 1 sharpless asymmetric epoxidation 2 chapter 6 alkyl halides nucleophilic substitution and elimination chapter 6 alkyl halides nucleophilic substitution and elimination 3 some common pesticides ddt lindane kepone aldrin chlordane 4 boiling point trends size of hydrocarbon part type of halogen of halogen atoms. Barry sharpless and coworkers now at scripps research institute and is commonly referred to as the sharpless asymmetric epoxidation. There are different reagents which can be used to accomplish this transformation. Alkene epoxidation reaction and mechanism using peroxy acid or mcpba. According to the criegee mechanism, 1,3dipolar cycloaddition.
The high enantioselectivity of this reaction is attributed to precoordination of the alcohol functional group to the titanium center. Stereoselective voacac2 catalyzed epoxidation of acyclic. Asymmetric epoxidation reactions with the advent of the sharpless asymmetric epoxidation reaction, developed in late 70s and early 80s, the epoxidation of both functionalized and unfunctionalized olefins has become an extremely important method for the synthesis of optically active compounds. The reaction is related to the sharpless dihydroxylation, which converts alkenes to vicinal diols. Sharpless asymmetric epoxidation the sharpless epoxidation is an organic reaction used to steroselectively convert an allylic alcohol to an epoxy alcohol using a titanium isopropoxide catalyst, tbutyl hydroperoxide tbhp, and a chiral diethyl tartrate det. 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. The jacobsen epoxidation, sometimes also referred to as jacobsenkatsuki epoxidation is a chemical reaction which allows enantioselective epoxidation of unfunctionalized alkyl and aryl substituted alkenes. Sharpless epoxidation dihydroxylations peracids baeyervilliger oxidation ozonolysis sharpless asymmetric epoxidations. 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. Substrate scope of ketone 1 o o o o o o 1 ph ph o 85% yield 98% ee c6h c6h 89%. Ohoh roh r r r r oh 90% ee r scope of the katsukisharpless asymmetric epoxidation oh 8695% ee r 9295% functional group compatibility.
However, mcpba can be explosive under some conditions. Myers sharpless asymmetric epoxidation reaction chem 115. A simplified catalytic cycle shows the formation of an mnvoxo complex. Sharpless asymmetric epoxidation of allylic alcohols. Sharpless, mechanism of the titaniumpromoted deoxygenative coupling of allyl and benzyl alcohols to hydrocarbons, j. For use as negative controls, we also extracted sohs from the amd. Sharpless epoxidation organic chemistry video clutch prep. Enantioselective epoxidation of allylic alcohols using tbutyl peroxide, titanium tetra isopropoxide, and optically pure diethyl tartrate. An exception is metachloroperoxybenzoic acid, shown in the mechanism above. Sharpless epoxidation dihydroxylations peracids baeyervilliger oxidation. Sharpless enantioselective epoxidation of achiral primary allyl alcohols is one.
The epoxidation reaction is the formation of an oxirane epoxide from an alkene. The sharpless epoxidation reaction is an enantioselective chemical reaction to prepare 2. In 1980, sharpless and katsuki discovered a system for the asymmetric epoxidation of primary allylic alcohols that utilizes tiopr. Apr 28, 2018 this organic chemistry video tutorial provides a basic introduction into the epoxidation of alkenes with peroxy acids such as mcpba and using the halohydrin formation reaction of alkenes followed. Guidelines for asymmetric epoxidation prepared by o. Nucleophilic epoxidation is the formation of epoxides from electrondeficient double bonds through the action of nucleophilic oxidants. Ohoh roh r r r r oh 90% ee r scope of the katsuki sharpless asymmetric epoxidation oh 8695% ee r 9295% functional group compatibility. We believe that the mechanism for the sharpless epoxidation can be generalized, and that the heterogeneously catalyzed propyle ne epoxidation step in. 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. Catalytic asymmetric epoxidation of allylic alcohols. The sharpless asymmetric epoxidation converts alkenes into chirally active epoxides innumerable syntheses published that use the sae chiral epoxides easily converted into. The sharpless epoxidation or sae, sharpless asymmetric epoxidation is an enantioselective epoxidation of allylic alcohols.
We believe that the mechanism for the sharpless epoxidation can be generalized, and that the heterogeneously catalyzed propyle ne epoxidation step in the smpo process proceeds in a similar fashion. Scope usage of aeadaa in natural product synthesis. The jacobsen epoxidation gains its stereoselectivity. Worlds best powerpoint templates crystalgraphics offers more powerpoint templates than anyone else in the world, with over 4 million to choose from. Feb 04, 2011 the vanadiumcatalyzed epoxidation reaction voacac 2 tbutyl hydroperoxide has become a very popular procedure for the stereoselective epoxidation of acyclic homoallylic alcohols. Metal ions or conjugate acids present in solution coordinate both the peroxide oxygen and the enolate oxygen. Enantioreversal in the sharpless asymmetric epoxidation reaction controlled by the molecular weight of a covalently appended achiral polymer. The sharpless asymmetric epoxidation is arguably one of the most important methods for the synthesis of enantiomerically enriched intermediates uses en route to a wide range of synthetic targets. Sharpless epoxidation of alkenes sharpless epoxidation of alkenes definition.
Sharpless asymmetric dihydroxylation sharpless ad chem. The active complex is believed to be two titanium atoms bridged by two tartrate ligands. In independent work, katsuki and jacobsen showed that asymmetric epoxidation occurs using manganese. Examples of the sharpless asymmetric epoxidation reaction in industry. The products of the sharpless epoxidation are predictable using the sharpless epoxidation model. Epoxidation of an asymmetrical alkene is usually a nonstereospecfic process, yielding a racemic mixture of enantiomers. The first of sharplesss reactions is the oxidation of an alkene by asymmetric epoxidation. Jun 16, 2016 watch more of this topic at download this pdf. Somewhere in one of your exams, you will see at least one question on epoxidation of alkenes. Mechanism in general, three different mechanisms possible for metal oxo epoxidation. Many students like to remember it as a cyclic ether. By changing the catalyst it is now possible to convert simple alkenes to the corresponding epoxide with highasymmetric induction.
Vicinal aminoalcohols are important products in organic synthesis and recurring pharmacophores in drug discovery. The sharpless oxyamination often known as sharpless aminohydroxylation is the chemical reaction that converts an alkene to a vicinal amino alcohol. The epoxidation reaction of cyclohexene is investigated for the system vanadyl acetylacetonate voacac 2 as catalyst with tertbutyl hydroperoxide tbhp as oxidant with the aim to identify the most active species for epoxidation and to retrieve. Enantioselective organocatalytic epoxidation using hypervalent iodine reagents. Theyll give your presentations a professional, memorable appearance the kind of sophisticated look that. Nucleophilic epoxidation methods represent a viable alternative to electrophilic methods, many of which do not epoxidize electronpoor double bonds efficiently. Nobel prize in 2001 contents biography introduction the need of epoxides background knowledge reagents reaction new synthetic approach modification references. The sharpless asymmetric epoxidation only works with allylic alcohols, as illustrated by the conversion of 156 to 157 or 158 to 159.
The mechanism begins with the displacement of the isopropoxide ligands on the titanium by det, tbhp, and finally by the allylic alcohol reagent. How do you select for one enantiomer over another side note. Ph co2et o o o aco oac h3c ch3 oo o ch h 3 hh ch h 3 o c ch ch3 ch3 oh h c ch 3 ph co2et o h3c ch3 ch3 ch3 ch3 ch3 ch3 oh ho ch3 o o o soojin kwon 1, oxone, dmm, ch3cn, h2o, ph 10. Reaction tolerates acetals, alkynes, alcohols, aldehydes, amides, azides, carbamates, epoxides, esters, ethers. Enantioselective organocatalytic epoxidation using. Mechanism and stereochemistry prevailing mechanism. An epoxide is a 3membered ring containing two carbon atoms and one oxygen atom.
The sharpless epoxidation allows the enantioselective epoxidation of prochiral allylic alcohols. For a good overview of mechanistic proposals please refer to t. The vanadiumcatalyzed epoxidation reaction voacac 2 tbutyl hydroperoxide has become a very popular procedure for the stereoselective epoxidation of acyclic homoallylic alcohols. An epoxidation model must be validated using hydroxylation data as a negative control to distinguish the epoxidation model from a general oxidation model. Winner of the standing ovation award for best powerpoint templates from presentations magazine. The mechanism of ethylene epoxidation citation for published version apa. The sharpless epoxidation is a named reaction that involves conversion of an asymmetric allylic alcohol to enantiomerically pure epoxide using a titanium alkoxide, an optically active tartrate ester, and an alkyl hydroperoxide. Sharpless, asymmetric epoxidation provides shortest routes to four chiral epoxy alcohols which are key intermediates in syntheses of methymycin. In this example, excess tbhp was quenched with triethylphosphite instead of feii sulfate. An epoxidation model should rank soes above sohs, whereas an oxidation model would rank them approximately equally. The mechanism of the reaction is not fully understood but the.
Apr 15, 2004 in 1980, sharpless and katsuki discovered a system for the asymmetric epoxidation of primary allylic alcohols that utilizes tiopr. Rates, kinetics, and mechanisms of epoxidation request pdf. Jacobsenkatsuki epoxidation organic chemistry portal. Sharpless epoxidation an overview sciencedirect topics. Notably, this reaction exhibits high levels of enantioselectivity usually 90% ee. The asymmetric induction is achieved by adding an enantiomerically enriched tartrate derivative. Sharpless epoxidation of alkenes the sharpless epoxidation or sae, sharpless asymmetric epoxidation is an enantioselective epoxidation of allylic alcohols. Barry sharples s nikki goodwin macmillan group meeting august 28, 2002 sharpless asymmetric epoxidation i. Compared to the sharpless epoxidation, the jacobsen epoxidation allows a broader substrate scope for the.
In this example, a stoichiometric amount of titanium and dipt was necessary for high conversion. A related zirconiumtartrate ligand system with cumene hydroperoxide was used for the enantioselective epoxidation of homoallyl alcohols. Sharpless asymmetric epoxidation the sharpless epoxidation is an organic reaction used to steroselectively convert an allylic alcohol to an epoxy alcohol using a titanium isopropoxide catalyst, tbutyl. Sharpless asymmetric epoxidation mcmaster university.