Substrate scope of ketone 1 o o o o o o 1 ph ph o 85% yield 98% ee c6h c6h 89%. Enantioreversal in the sharpless asymmetric epoxidation reaction controlled by the molecular weight of a covalently appended achiral polymer. 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. Sharpless epoxidation of alkenes sharpless epoxidation of alkenes definition.
This transformation provides rapid access to enantioenriched 1,2transformyl epoxides, an ambiphilic class of electrophile of known value in chemical synthesis. Myers sharpless asymmetric dihydroxylation reaction chem 115. 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. The rate of titaniumtartratecatalyzed asymmetric epoxidation of allylic alcohols is shown to. In independent work, katsuki and jacobsen showed that asymmetric epoxidation occurs using manganesesalen catalysts in the presence. Development of jacobsen asymmetric epoxidation and sharpless asymmetric dihydroxylation methods for the largescale preparation of a chiral dihydrobenzofuran epoxide. The active complex is believed to be two titanium atoms bridged by two tartrate ligands. The application of organocatalytic asymmetric epoxidation.
The sharpless epoxidation or sae, sharpless asymmetric epoxidation is an enantioselective epoxidation of allylic alcohols. Synthetic applications of chiral unsaturated epoxy. The shi epoxidation allows the synthesis of epoxides from various alkenes using a fructosederived organocatalyst with oxone as the primary oxidant. The sharpless lab was the first academic chemistry group with robotics, and the lesson from the combinatorial numbers game was the primacy of reliability. In catalytic asymmetric synthesis, 2nd ed ojima, i. Notably, this reaction exhibits high levels of enantioselectivity usually 90% ee.
Feb 11, 2016 sharpless asymmetric epoxidation reaction explain in hindi duration. Catalytic asymmetric epoxidation of allylic alcohols. The absolute configuration of the epoxide products depends only on the absolute configuration of the det ligand see the empirical rule shown below. Pdf development of jacobsen asymmetric epoxidation and. 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. The sharpless asymmetric epoxidation converts alkenes into chirally active epoxides innumerable syntheses published that use the sae chiral epoxides easily converted into. These are not indefinitely stable, but can be generated in situ by oxidation of a ketone with potassium peroxymonosulfate oxone. Sharpless asymmetric epoxidation of allylic alcohols. Unsaturated epoxides prepared by sharpless asymmetric epoxidation. 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 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. Ligands such as pyridine accelerate the osmylation of ole. 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.
In this example, excess tbhp was quenched with triethylphosphite instead of feii sulfate. General characteristicsthe asymmetric epoxidation of allylic alcohols using catalytic tio i pr 4, diethyl tartrate det, and tbutyl hydroperoxide tbhp is known as the sharplesskatsuki reaction. B catalytic asymmetric epoxidation of allylic alcohols. Converts primary and secondary allylic alcohols into 2,3 epoxyalcohols. Preparation of epoxy alcohol 2 using either sharpless asymmetric epoxidation sae or the methodology developed by jagger, which combines sae and payne rearrangement. 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 sharpless epoxidation allows the enantioselective epoxidation of prochiral allylic alcohols. The catalyst is easily prepared from fructose and displays broad generality. The sharpless epoxidation reaction is an enantioselective chemical reaction to prepare 2,3epoxyalcohols from primary and secondary allylic alcohols. These are not indefinitely stable, but can be generated in situ by. 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. Asymmetric epoxidation using shi catalyst technical. Myers sharpless asymmetric epoxidation reaction chem 115.
Physical chemistry inorganic chemistry organic chemistry organic synthesis asymmetric synthesis these keywords were added by machine and not by the authors. The sulfate as a good leaving group facilitates the ring closure to the dioxiranes. 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. Enantioselective organocatalytic epoxidation using. Asymmetric epoxidation kinetic resolution r 2r1 r3 oh r4 h r r1 r3 oh h r4 ddiethyl tartrate unnatural slow fast. Sharplesskatsuki asymmetric epoxidation sharpless ae. Apr 15, 2004 in 1980, sharpless and katsuki discovered a system for the asymmetric epoxidation of primary allylic alcohols that utilizes tiopr. Sharpless, discovery of the titaniumcatalyzed asymmetric epoxidationa personal account. Notably, this reaction exhibits high levels of enantioselectivity usually. This process is experimental and the keywords may be updated as the learning algorithm improves. Epoxides are very useful intermediates in organic synthesis.
So the whole point of this reaction is that its a form of epoxidation that is enantioselective. Ti oipr, rzogh r3 4 70 87% y elds 0 7 90 % e e ll pdf page id 28256. Enantioselective epoxidation of allylic alcohols using tbutyl peroxide, titanium tetra isopropoxide, and optically pure diethyl tartrate. The active complex is believed to be two titanium atoms bridged by. By adding a chiral ligand to the titanium catalyst the reaction becomes asymmetric. By changing the catalyst it is now possible to convert simple alkenes to the corresponding epoxide with high asymmetric induction. Sharpless asymmetric dihydroxylation sharpless ad chem. Turnover is achieved by reoxidation with stoichiometric oxidants. 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. 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. Epoxy alcohol structure yield % ee % references 2 n. Applications of sharpless asymmetric epoxidation in total synthesis this report presents the applications of. The name of this reaction is the sharpless asymmetric epoxidation.
The epoxidizing species is believed to be a dioxirane, which is a powerful epoxidation reagent. Welch foundation conferences on chemical research xxvii stereospecificity in chemistry and biochemistry, november 79, 1983, houston, tx. 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. Although the most commonly used asymmetric epoxidation methods the sharpless katsuki, and jacobsen epoxidations rely on the catalytic reactivity of electrophilic oxidants, nucleophilic oxygen sources substituted with a suitable leaving group can also act as epoxidation reagents. Sharpless epoxidation organic chemistry video clutch prep. The sharpless asymmetric epoxidation only works with allylic alcohols, as illustrated by the conversion of 156 to 157 or 158 to 159. The oxidant for the epoxidation is tert butyl hydroperoxide. In 1980, sharpless and katsuki discovered a system for the asymmetric epoxidation of primary allylic alcohols that utilizes tiopr. Sharplesskatsuki epoxidation in name reactions in heterocyclic chemistry. Sharpless asymmetric epoxidation mcmaster university. Sharpless enantioselective epoxidation of achiral primary allyl alcohols. Enantioselective epoxidation of allylic alcohols using tbutyl peroxide, titanium tetraisopropoxide, and optically pure diethyl.
Epoxidation reactionvery important topic for jam,net. Barry sharpless and coworkers now at scripps research institute and is commonly referred to as the sharpless asymmetric epoxidation. 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. 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. Myers sharpless asymmetric dihydroxylation reaction chem.
Jun 25, 2009 enantioselective epoxidation of allylic alcohols using tbutyl peroxide, titanium tetra isopropoxide, and optically pure diethyl tartrate. The nature of the katsukisharpless asymmetric epoxidation catalyst. 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. The first of sharplesss reactions is the oxidation of an alkene by asymmetric epoxidation. 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. Nobel prize in 2001 contents biography introduction the need of epoxides background knowledge reagents reaction new synthetic approach modification references. Examples of the sharpless asymmetric epoxidation reaction in industry. In this example, a stoichiometric amount of titanium and dipt was necessary for high conversion. The journal of organic chemistry 2005, 70 5, 17281731.
Guidelines for asymmetric epoxidation prepared by o. Request pdf sharpless asymmetric epoxidation enantioselective epoxidation of allylic alcohols using tbutyl peroxide, titanium tetraisopropoxide, and optically pure diethyl tartrate. Asymmetric epoxidation of allylic alcoholsa 3lidietnyl tartrcte jnncturol 1. The application of organocatalytic asymmetric epoxidation mohammed i.
1264 891 202 1298 705 512 1058 35 1263 136 1061 1030 1191 197 872 827 1528 816 35 166 1038 615 1254 1459 1100 1012 1236 1293