Synthetic applications of chiral unsaturated epoxy alcohols. Unsaturated epoxides prepared by sharpless asymmetric epoxidation. The application of organocatalytic asymmetric epoxidation mohammed i. These are not indefinitely stable, but can be generated in situ by oxidation of a ketone with potassium peroxymonosulfate oxone. The application of organocatalytic asymmetric epoxidation. The stereochemistry of the resulting epoxide is determined by the enantiomer of the chiral tartrate diester usually diethyl tartrate or diisopropyl tartrate employed in the reaction.
The name of this reaction is the sharpless asymmetric epoxidation. Notably, this reaction exhibits high levels of enantioselectivity usually. 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 sharpless epoxidation allows the enantioselective epoxidation of prochiral allylic alcohols. Sharpless asymmetric epoxidation of allylic alcohols. Epoxides are very useful intermediates in organic synthesis. Sharpless, discovery of the titaniumcatalyzed asymmetric epoxidationa personal account. The first of sharplesss reactions is the oxidation of an alkene by asymmetric epoxidation. What that means is that its going to generate only one of the two possible enantiomers in excess. Welch foundation conferences on chemical research xxvii stereospecificity in chemistry and biochemistry, november 79, 1983, houston, tx.
In this example, a stoichiometric amount of titanium and dipt was necessary for high conversion. Sharplesskatsuki epoxidation in name reactions in heterocyclic chemistry. Jp2012201651a sharpless asymmetric epoxidation reaction. Apr 15, 2004 in 1980, sharpless and katsuki discovered a system for the asymmetric epoxidation of primary allylic alcohols that utilizes tiopr. The sharpless asymmetric epoxidation only works with allylic alcohols, as illustrated by the conversion of 156 to 157 or 158 to 159. Sharpless asymmetric epoxidation mcmaster university. Turnover is achieved by reoxidation with stoichiometric oxidants. Guidelines for asymmetric epoxidation prepared by o. Because most naturally occurring molecules including those with medicinal properties are chiral, control of stereochemistry is one of the most important challenges facing a synthetic chemist attempting to synthesize a naturally occurring molecule in.
Myers sharpless asymmetric epoxidation reaction chem 115. Asymmetric epoxidation using shi catalyst technical. By changing the catalyst it is now possible to convert simple alkenes to the corresponding epoxide with highasymmetric induction. On thenature of the katsukisharpless asymmetric epoxidation catalyst. 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. This process is experimental and the keywords may be updated as the learning algorithm improves. 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. Iminiumcatalysed asymmetric epoxidation methodology has been applied to the synthesis of levcromakalim, 3 trans khellactone, and lomatin, 4 which are based on a chromenetype structure. Sharpless enantioselective epoxidation of achiral primary allyl alcohols. Barry sharpless and coworkers now at scripps research institute and is commonly referred to as the sharpless asymmetric epoxidation. Sharpless asymmetric epoxidation racemic allylic alcohols are treated with a half equivalent of terrbutyl hydroperoxide in the presence of chiral catalysts, titanium tetraisopropoxide complexed with d or lethyl tartrate. The nature of the katsukisharpless asymmetric epoxidation catalyst.
Epoxy alcohol structure yield % ee % references 2 n. Enantioselective epoxidation of allylic alcohols using tbutyl peroxide, titanium tetraisopropoxide, and optically pure diethyl. The journal of organic chemistry 2005, 70 5, 17281731. Bayervilliger oxidations ketones react with peroxyacids or hydrogen peroxides to give. The sharpless asymmetric epoxidation converts alkenes into chirally active epoxides innumerable syntheses published that use the sae chiral epoxides easily converted into. By adding a chiral ligand to the titanium catalyst the reaction becomes asymmetric. The catalyst is easily prepared from fructose and displays broad generality. 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. B catalytic asymmetric epoxidation of allylic alcohols. Ti oipr, rzogh r3 4 70 87% y elds 0 7 90 % e e ll pdf page id 28256. The shi epoxidation allows the synthesis of epoxides from various alkenes using a fructosederived organocatalyst with oxone as the primary oxidant. Enantioselective epoxidation of allylic alcohols using tbutyl peroxide, titanium tetra isopropoxide, and optically pure diethyl tartrate.
The asymmetric epoxidation of allylic alcohols using catalytic tio i pr 4, diethyl tartrate det, and tbutyl hydroperoxide tbhp is known as the sharpless katsuki reaction. Pdf development of jacobsen asymmetric epoxidation and. 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. Feb 11, 2016 sharpless asymmetric epoxidation reaction explain in hindi duration.
Sharpless epoxidation of alkenes the sharpless epoxidation or sae, sharpless asymmetric epoxidation is an enantioselective epoxidation of allylic alcohols. 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. Ligands such as pyridine accelerate the osmylation of ole. In this example, excess tbhp was quenched with triethylphosphite instead of feii sulfate. By changing the catalyst it is now possible to convert simple alkenes to the corresponding epoxide with high asymmetric induction. Asymmetric epoxidation kinetic resolution r 2r1 r3 oh r4 h r r1 r3 oh h r4 ddiethyl tartrate unnatural slow fast. In 1980, sharpless and katsuki discovered a system for the asymmetric epoxidation of primary allylic alcohols that utilizes tiopr. Examples of the sharpless asymmetric epoxidation reaction in industry.
These are not indefinitely stable, but can be generated in situ by. Sharpless epoxidation of alkenes sharpless epoxidation of alkenes definition. Request pdf sharpless asymmetric epoxidation enantioselective epoxidation of allylic alcohols using tbutyl peroxide, titanium tetraisopropoxide, and optically pure diethyl tartrate. This transformation provides rapid access to enantioenriched 1,2transformyl epoxides, an ambiphilic class of electrophile of known value in chemical synthesis.
The asymmetric induction is achieved by adding an enantiomerically enriched tartrate derivative. The sharpless lab was the first academic chemistry group with robotics, and the lesson from the combinatorial numbers game was the primacy of reliability. The key asymmetric steps include in particular a highly enantioselective organocatalyzed michael addition on an aryl vinyl ketone, a sharpless asymmetric epoxidation and a subsequent. Substrate scope of ketone 1 o o o o o o 1 ph ph o 85% yield 98% ee c6h c6h 89%. Notably, this reaction exhibits high levels of enantioselectivity usually 90% ee. The oxidant for the epoxidation is tert butyl hydroperoxide. Nobel prize in 2001 contents biography introduction the need of epoxides background knowledge reagents reaction new synthetic approach modification references. Applications of sharpless asymmetric epoxidation in total synthesis this report presents the applications of. Preparation of epoxy alcohol 2 using either sharpless asymmetric epoxidation sae or the methodology developed by jagger, which combines sae and payne rearrangement. Sharpless asymmetric epoxidation sae converts primary and secondary allylic alcohols into 2,3 epoxyalcoholsthe reaction is enantioselective only one enantiomer producedenantiomer formed depends on stereochemistry of catalyst. 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 jacobsen katsuki. Alahmdi in the field of research of target natural product synthesis, catalytic asymmetric synthesis has become a vital tool to obtain enantiomerically pure compounds, and is often used in the.
In independent work, katsuki and jacobsen showed that asymmetric epoxidation occurs using manganesesalen catalysts in the presence. Converts primary and secondary allylic alcohols into 2,3 epoxyalcohols. Myers sharpless asymmetric dihydroxylation reaction chem. The epoxidizing species is believed to be a dioxirane, which is a powerful epoxidation reagent. Sharplesskatsuki asymmetric epoxidation sharpless ae. 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. Development of jacobsen asymmetric epoxidation and sharpless asymmetric dihydroxylation methods for the largescale preparation of a chiral dihydrobenzofuran epoxide. Enantioselective organocatalytic epoxidation using. Sharpless epoxidation organic chemistry video clutch prep. The sulfate as a good leaving group facilitates the ring closure to the dioxiranes. The present invention provides a method for efficiently proceeding sharpless asymmetric epoxidation without adding molecular sieves. In catalytic asymmetric synthesis, 2nd ed ojima, i.
Sharpless asymmetric dihydroxylation sharpless ad chem. The active complex is believed to be two titanium atoms bridged by. The absolute configuration of the epoxide products depends only on the absolute configuration of the det ligand see the empirical rule shown below. Catalytic asymmetric epoxidation of allylic alcohols. The sharpless epoxidation reaction is an enantioselective chemical reaction to prepare 2,3epoxyalcohols from primary and secondary allylic alcohols. The sharpless epoxidation or sae, sharpless asymmetric epoxidation is an enantioselective epoxidation of allylic alcohols. Jun 25, 2009 enantioselective epoxidation of allylic alcohols using tbutyl peroxide, titanium tetra isopropoxide, and optically pure diethyl tartrate.
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