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