Catalyst for the enantioselective epoxidation of alkenes. Jun 25, 2009 enantioselective epoxidation of allylic alcohols using tbutyl peroxide, titanium tetra isopropoxide, and optically pure diethyl tartrate. 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 absolute configuration of the epoxide products depends only on the absolute configuration of the det ligand see the empirical rule shown below. Asymmetric epoxidation using shi catalyst technical.
Synthetic applications of chiral unsaturated epoxy alcohols. In this example, excess tbhp was quenched with triethylphosphite instead of feii sulfate. Sharpless epoxidation organic chemistry video clutch prep. Application of sharpless asymmetric epoxidation on the. B catalytic asymmetric epoxidation of allylic alcohols. Sharpless asymmetric epoxidation of alkenes youtube.
Asymmetric synthesis the use of a chiral manganese catalyst for. Ligands such as pyridine accelerate the osmylation of ole. Advances in homogeneous and heterogeneous catalytic. Sharpless epoxidation of alkenes the sharpless epoxidation or sae, sharpless asymmetric epoxidation is an enantioselective epoxidation of allylic alcohols. The application of organocatalytic asymmetric epoxidation.
Barry sharpless and coworkers now at scripps research institute and is commonly referred to as the sharpless asymmetric epoxidation. Enantioselective organocatalytic epoxidation using. Turnover is achieved by reoxidation with stoichiometric oxidants. Sharpless is best known for discovering three name reactions, general methods for catalytic asymmetric epoxidation, dihydroxylation, and aminohydroxylation. 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. Sharpless asymmetric dihydroxylation also called the sharpless bishydroxylation is the chemical reaction of an alkene with osmium tetroxide in the presence of a chiral quinine ligand to form a vicinal diol. The sharpless asymmetric epoxidation only works with allylic alcohols, as illustrated by the conversion of 156 to 157 or 158 to 159. The reaction has been applied to alkenes of virtually every substitution, often high enantioselectivities are realized. 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. Guidelines for asymmetric epoxidation prepared by o. Sharpless asymmetric epoxidation mcmaster university.
Ready enantioselective epoxidation with dioxiranes several groups have developed chiral ketones as catalysts for asymmetric epoxidation. 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. With r, r tartrate the 16,17epoxide laulimalide 1 is formed selectively, whereas s, s tartrate generates the 21,22epoxide 142. Enantioselectivity is achieved through the addition of dihydroquinine and dihydroquinidinederived chiral ligands. Converts primary and secondary allylic alcohols into 2,3 epoxyalcohols. Asymmetric epoxidation using shi catalyst technical article. I didnt use any molecular sieves, so there was probably some adventitious water despite using dried solvent, and the bottle of det i used was pretty old. A twinned laboratory and molecular modeling experiment for upperlevel organic chemistry students. Dec 12, 2017 sharpless epoxidation reaction and its extension is useful in any advance chemistry exam like netgateupscgre etc. The name of this reaction is the sharpless asymmetric epoxidation. However, in some instances, the yield of an amino alcohol product and the regioselectivity could be altered by the addition of a catalytic. Pdf asymmetric synthesis of azidotetrahydropyranols via. 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. The active complex is believed to be two titanium atoms bridged by.
His nobel prize citation says, many scientists have identi. Epoxide opening reactions recent advances and synthetic. Pdf development of jacobsen asymmetric epoxidation and. Asymmetric dihydroxylation of alkenes can be modified to synthesize chiral amino alcohols, 429 in what is known as sharpless asymmetric aminohydroxylation or oxyamination. Pdf enantioselective synthesis of deoxymannojirimycin. General characteristicsthe 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. Jan 11, 2015 sharpless epoxidation is the enantioselective epoxidation of prochiral allylic alcohols. The reaction uses 510 mol % of the catalyst in the presence of 3a molecular sieves. The sharpless epoxidation reaction is an enantioselective chemical reaction to prepare 2,3epoxyalcohols from primary and secondary allylic alcohols. Oct 01, 2015 asymmetric epoxidation also called the sharpless epoxidation reaction is a method of preparing chiral epoxides from prochiral allylic alcohols. Epoxidation reactionvery important topic for jam,net. Enantioselective synthesis of deoxymannojirimycin based on sharpless asymmetric epoxidation of a highly functionalized allylic alcohol.
Compared to the sharpless epoxidation, the jacobsen epoxidation allows a broader substrate scope for the transformation. This asymmetric epoxidation, now known as the sharpless epoxidation, has already shown its power in the synthesis of natural products. The first of sharpless s reactions is the oxidation of an alkene by asymmetric epoxidation. The vanadiumcatalyzed epoxidation reaction voacac 2 tbutyl hydroperoxide has become a very popular procedure for the stereoselective epoxidation of acyclic homoallylic alcohols.
In independent work, katsuki and jacobsen showed that asymmetric epoxidation occurs using manganesesalen catalysts in the presence. Applications of sharpless asymmetric epoxidation in total synthesis this report presents the applications of. Barry sharples s nikki goodwin macmillan group meeting august 28, 2002 sharpless asymmetric epoxidation i. Asymmetric dihydroxylation an overview sciencedirect. Asymmetric epoxidation kinetic resolution r 2r1 r3 oh r4 h r r1 r3 oh h r4 ddiethyl tartrate unnatural slow fast.
Epoxidation of allylic alcohols by titaniumtartrate. In general, in the absence of a ligand, the reaction provided racemic fmocprotected amino alcohols with excellent regioselectivity but in low to moderate yields. Asymmetric stereoselective synthesis sharpless asymmetric id ti drugsynthesis ii n n n h n oh o oh hn o crixivan indinavir hivproteaseinibitor epox a on jacobsen asymmetric epoxidation diastereoselective alkylation resolution tapio nevalainen 2012 streoselectivity stereoselective reactions reactions where one. This transformation provides rapid access to enantioenriched 1,2transformyl epoxides, an ambiphilic class of electrophile of known value in chemical synthesis. The journal of organic chemistry 2019, article asap. By changing the catalyst it is now possible to convert simple alkenes to the corresponding epoxide with high asymmetric induction. Development of jacobsen asymmetric epoxidation and sharpless asymmetric dihydroxylation methods for the largescale preparation of a chiral dihydrobenzofuran epoxide. The sharpless asymmetric epoxidation sae is among the most powerful enantioselective catalytic reactions available.
The sharpless aminohydroxylation allows the synselective preparation of 1,2amino alcohols by reaction of alkenes with salts of nhalosulfonamides, amides and carbamates using oso 4 as a catalyst. By adding a chiral ligand to the titanium catalyst the reaction becomes asymmetric. 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 enantiomer of the diethyl tartrate determines the stereochemistry of the. Jacobsenkatsuki epoxidation organic chemistry portal. Epoxidation, dihydroxylation, and the utility of epoxides and diols ready. Myers sharpless asymmetric epoxidation 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. 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. Applications of sharpless asymmetric epoxidation in total. 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. Myers sharpless asymmetric dihydroxylation reaction chem. Jesse teske, andy flick, daniel schmitt oh oh dipt, tioipr4, tbhp o naoh oet oh. 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. Substrate scope of ketone 1 o o o o o o 1 ph ph o 85% yield 98% ee c6h c6h 89%. The literature value is around 90%, but i only got 50%. Sharpless asymmetric epoxidation of allylic alcohols. Bayervilliger oxidations ketones react with peroxyacids or hydrogen peroxides to give. In this example, excess tbhp was quenched with triethylphosphite instead of fe ii sulfate. Stereoselective voacac2 catalyzed epoxidation of acyclic.
Asymmetric epoxidation of allylic alcoholsa 3lidietnyl tartrcte jnncturol 1. Pdf efficient soluble polymersupported sharpless alkene. Sharpless aminohydroxylation sharpless oxyamination. Sharpless systems as shown in scheme 1, four epoxides racemic 2 and 3 from geraniol 1 are possibly made through improving either regio or chemoselectivity, while the. Catalytic asymmetric epoxidation using a fructosederived. The aminohydroxylation of various alkenes using fmocnhcl as a nitrogen source is reported. Sharpless, procedure for the catalytic asymmetric epoxidation of allylic alcohols in the presence of molecular sieves, j. The sharpless asymmetric epoxidation converts alkenes into chirally active epoxides innumerable syntheses published that use the sae chiral epoxides easily converted into. 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. Sharpless asymmetric epoxidation sae converts primary and secondary allylic alcohols into 2,3 epoxyalcoholsthe reaction is enantioselective only one enantiomer produced enantiomer formed depends on stereochemistry of catalyst. This wellknown reaction comprises enantioselective epoxidation of an allyl alcohol using tertbutyl hydroperoxide as oxidant.
Asymmetric synthesis of azidotetrahydropyranols via sharpless epoxidation article pdf available in archive for organic chemistry 20023 march 2002 with 25 reads how we measure reads. The catalyst is a complex formed from titaniumiv isopropoxide and diethyl tartrate det. Jm chong and kb sharpless nucleophilic opening of 23 epoxy. Myers sharpless asymmetric dihydroxylation reaction chem 115. Reading mode part one on this topic showed how a quantum mechanical model employing just one titanium centre was not successful in predicting the stereochemical outcome of the sharpless asymmetric epoxidation. This report presents the applications of enantioselective epoxidation of prochiral allylic alcohols, so called sharpless asymmetric epoxidation, which is frequently referred as kinetic resolution. Epoxidation condensation approaches darzens condensation sulfur ylides with organic peroxides peroxy acids peroxy iminic acids dioxiranes dmdo enantioselective versions metalcatalyzed approaches voacac. 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.
Electronic and steric factors determining the asymmetric. So2f2mediated epoxidation of olefins with hydrogen peroxide. The unprotected deoxy derivative 3 was subjected to sharpless asymmetric epoxidation sae. 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. The application of organocatalytic asymmetric epoxidation mohammed i. Efficient soluble polymersupported sharpless alkene epoxidation catalysts article pdf available in chemical communications february 2002 with 33 reads how we measure reads. In catalytic asymmetric synthesis, 2nd ed ojima, i. Myers sharpless asymmetric dihydroxylation reaction chem 115 2. In 1980, sharpless and katsuki discovered a system for the asymmetric epoxidation of primary allylic alcohols that utilizes tiopr. Sharplesskatsuki asymmetric epoxidation sharpless ae. Examples of the sharpless asymmetric epoxidation reaction in industry. What that means is that its going to generate only one of the two possible enantiomers in excess. Asymmetric catalysis using chiral salenmetal complexes.
Feb 10, 2017 sharpless asymmetric epoxidation trick reagents part2 for csirnet gate iit jam 2019 duration. Synthetic applications of chiral unsaturated epoxy alcohols prepared by sharpless asymmetric epoxidation. In this example, a stoichiometric amount of titanium and dipt was necessary for high conversion. The first practical method for asymmetric epoxidation. Total synthesis of the microtubule stabilizing antitumor. Enantioselective epoxidation of allylic alcohols using tbutyl peroxide, titanium tetra isopropoxide, and optically pure diethyl tartrate.
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