Applications of sharpless asymmetric dihydroxylation in. Applications of sharpless asymmetric dihydroxylation in total. Catalytic asymmetric dihydroxylation of alkenes aims of the experiment to prepare an enantiomerically enriched 1,2diol using sharpless catalytic asymmetric dihydroxylation procedure, and to estimate the enantiomeric purity of the material you obtain. However, there are limitations to performing the catalytic ad reaction on a large scale due to the toxicity of osmium tetroxide and the high cost of preparing the cinchona alkaloid ligands. Racemic dihydroxylation of alkenes is efficiently accomplished with catalytic osmium added as oscl 3, stoichiometric k 3 fecn 6 and quinuclidine under conditions similar to those of the sharpless asymmetric hydroxylation.
Sharpless asymmetric dihydroxylation reaction is the chemical reaction of an alkene with osmium tetroxide in the presence of a chiral quinine ligand to provide an optically active vicinal diol. Myers sharpless asymmetric dihydroxylation reaction chem 115. The journal of organic chemistry 2011, 76 20, 85548559. Mechanism of the sharpless asymmetric dihydroxylation. The mnemonic device for predicting the face selectivity 1. Sharpless asymmetric dihydroxylation use a premix of reagent components the ligand accelerates the reaction transfers the chiral information m. Scalable synthesis of enantiomerically pure syn2,3dihydroxybutyrate by sharpless asymmetric dihydroxylation of pphenylbenzyl crotonate.
Epoxidation, dihydroxylation, and the utility of epoxides and diols ready outline. Scalable synthesis of enantiomerically pure syn2,3. An eycient protocol for sharpless style racemic dihydroxylation jason eames,a helen j. Nov 19, 2017 stereospecific and stereoselective reactions asymmetric synthesis elementary idea duration.
In the reaction conditions used in sharpless asymmetric dihydroxylation, weakly acidic methanesulfonamide was found to be a general acid catalyst that protonates the intermediate osmate esters of conjugated aromatic olefins in the hydrolysis step. Multigramme synthesis and asymmetric dihydroxylation of a. Myers sharpless asymmetric dihydroxylation reaction chem 115 2. This process is experimental and the keywords may be updated as the learning algorithm improves. Marko, ligandaccelerated catalytic asymmetric dihydroxylation using dihydroquinidine and dihydroquinidine esters as ligands, u. Asymmetric dihydroxylation of alkenes brought to you by the organic reactions wiki, the online collection of organic reactions jump to. Relatively large volumes of organic extractant were necessary to isolate the highly watersoluble product, and chromatographic. Asymmetric dihydroxylation and aziridination of allenes and related chemistry renmao liu department of chemistry and biochemistry doctor of philosophy a novel method for asymmetric synthesis of. The sharpless asymmetric aminohydroxylation scope and limitation. The sharpless asymmetric dihydroxylation protocol, using enriched admix. Parasubstituents are shown to favor high enantioselectivity 8995%ee, while orthogroups have a deleterious effect. Sharpless asymmetric epoxidation mcmaster university. 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. Enantioselective cisdihydroxylation of olefins using osmium catalyst in the presence of cinchona alkaloid ligands.
Asymmetric dihydroxylation of substituted aryl allyl ethers is described. The synthesis starts from 4methoxystyrene 9, a commercially available starting material. The inspiration for the new approach outlined here comes from nature. We briefly investigated conditions to shorten the reaction time. To obtain information about the effect that methanesulfonamide has in the hydrolysis step in sharpless asymmetric dihydroxylation, a series of aliphatic and conjugated aromatic olefins were dihydroxylated with and without methanesulfonamide. 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 hypothesis in this study was that methanesulfonamide is a cosolvent that aids in the transfer of the hydroxide ions from the water phase to the. Mitchell,a adam nelson,a peter obrien,a stuart warrena and paul wyattb a university chemical laboratory, lensweld road, cambridge, uk cb2 1ew b school of chemistry, cantocks close, bristol, uk bs8 1ts. Asymmetric dihydroxylation of alkenes organic reactions wiki. The importance of the choice of benzyl protecting group at c 38 is illustrated by the fact that the analogous tbs ether underwent dihydroxylation under the same conditions with markedly reduced facial selectivity. The benefits of the optimized sharpless asymmetric dihydroxylation reactionexcellent yield and enantioselectivitywere somewhat offset by the length of the reaction time in the optimized protocol 5 d, referred to as method a table 2, entry 1. Asymmetric dihydroxylation of 1hexene using diferent surfactants at 0.
The corresponding isolated yields under these conditions. General characteristics sharpless developed chiral ligands dhqd2phal or dhq2phal derived from cinchona alkaloids quinidine, quinine for the practical osmium tetroxidecatalyzed asymmetric dihydroxylation reaction. The sharpless lab was the first academic chemistry group with robotics, and the lesson from the combinatorial numbers game was the primacy of reliability. Oct 21, 2011 the benefits of the optimized sharpless asymmetric dihydroxylation reactionexcellent yield and enantioselectivitywere somewhat offset by the length of the reaction time in the optimized protocol 5 d, referred to as method a table 2, entry 1. Sharpless asymmetric dihydroxylation of olefins in. 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. Synthesis of some new 2substituted 4,5dihydroxypiperidines. Applications of sharpless asymmetric dihydroxylation in the. An early attempt at the asymmetric epoxidation of unfunctionalised alkenes used molybdenum species and tartrate esters, but gave low levels of asymmetric induction. Sharpless asymmetric dihydroxylation is the chemical reaction of an alkene with osmium tetroxide in the presence of a chiral quinine ligand to form a vicinal diol.
The aim of this study is to present the applications of sharpless asymmetric dihydroxylation sad also called the sharpless bishydroxylation. Multigramme synthesis and asymmetric dihydroxylation of a 4. Asymmetric dihydroxylation and aziridination of allenes and. In this example, excess tbhp was quenched with triethylphosphite instead of feii sulfate. Examples of the sharpless asymmetric epoxidation reaction in industry. Sad is the chemical reaction of an alkene with osmium tetroxide in the presence of a chiral quinine ligand to form an optically pure vicinal diol. Asymmetric dihydroxylation and aziridination of allenes. Stereospecific and stereoselective reactions asymmetric synthesis elementary idea duration. The sharpless asymmetric epoxidation converts alkenes into chirally active epoxides innumerable syntheses published that use the sae chiral epoxides easily converted into. An asymmetric dihydroxylation route to roctopamine.
The sharpless epoxidation reaction is considered one of the most powerful advances in asymmetric organic synthesis 1. Part of thebiochemistry commons, and thechemistry commons this dissertation is brought to you for free and open access by byu scholarsarchive. O o n ome n meo h n n et et n n o o n ome n meo h n n et et ome n n otms n nh n h ome nh s cf 3 f 3 c n nh 2. Table 4 dihydroxylation of the allylic phosphine oxide 18 starting material oxidant. Myers sharpless asymmetric epoxidation reaction chem 115 a further example of anomalous stereochemistry in ae of an allylic diol no reaction with dipt. An efficient protocol for sharplessstyle racemic dihydroxylation. The reaction has been applied to alkenes of virtually every substitution, often high enantioselectivities are realized. Wittig approach and sharpless asymmetric dihydroxylation reaction towards the synthesis of 3hydroxylproline and tedanalactam mulzer j. Karl barry sharpless developed stereoselective oxidation. Scalable synthesis of enantiomerically pure dihydroxybutyrate. The reason that they attach in a cis manner is because of how the reaction occurs. The catalytic asymmetric dihydroxylation is performed in a 1. Asymmetric dihydroxylation of olefins using cinchona.
Enantioselective cis dihydroxylation of olefins using osmium catalyst in the presence of cinchona alkaloid ligands. The procedure typically uses titaniumiv tetraisopropoxide tioipr4 as a catalyst, a peroxide, and dialkyl tartrates to induce asymmetry in the. Turnover is achieved by reoxidation with stoichiometric oxidants. Myers sharpless asymmetric dihydroxylation reaction chem.
Ch11 chemical engg, chemistry and others 21,528 views 30. Sharpless asymmetric reactions require an osmonium catalyst and a. Asymmetric dihydroxylation and aziridination of allenes and related chemistry renmao liu brigham young university provo follow this and additional works at. 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. Rama rao arkivoc 2005 iii 3643 issn 14246376 page 38 arkat usa, inc the synthetic route to rtembamide 2 and raegeline 3 is shown in scheme 2. Recent advances on the sharpless asymmetric aminohydroxylation. It is common practice to perform this reaction using a catalytic amount of osmium tetroxide, which after reaction is regenerated with either potassium ferricyanide. Inorganic chemistry organic chemistry nobel prize cinchona alkaloid asymmetric dihydroxylation these keywords were added by machine and not by the authors. I was hoping some of you chemistry masters could help a girl out. Pdf the sharpless asymmetric aminohydroxylation scope. In this example, a stoichiometric amount of titanium and dipt was necessary for high conversion.
The literature value is around 90%, but i only got 50%. Chiral ligands for asymmetric aminohydroxylation aa 1980 n l22menthyl pyridine n o n n ho dhq 2phal n h dihydroquinidine acetate dihydroquinine acetate n n h oac et n et aco ome meo 1996 li, g chang, h sharpless, k. It is a classic example of the use of an asymmetric catalyst to provide an enantiomerically enriched mixture of epoxy alcohols. It is common practice to perform this reaction using a catalytic amount of osmium tetroxide, which after reaction is regenerated with either. Ligands such as pyridine accelerate the osmylation of ole. Wittig approach and sharpless asymmetric dihydroxylation. Jun 25, 2009 inorganic chemistry organic chemistry nobel prize cinchona alkaloid asymmetric dihydroxylation these keywords were added by machine and not by the authors.
O n n n n h et meo n h ome et n n et ome et dhqd 2phal. S patent 4,871,855, 1989 assigned to the massachusetts institute of technology. Sharpless asymmetric dihydroxylation continued youtube. Csir net chemical science solved question june 2017,woodward reaction and prevost reaction in hindi duration. Sharpless asymmetric dihydroxylation sharpless ad chem. Meo2cme2, pocl3 ochph 2 sph o o paynerearrangement. Reaction conditions the catalytic asymmetric dihydroxylation is performed in a 1.
Asymmetric synthesis of aryloxypropanolamines via oso4. The stereochemistry of the resulting epoxide is determined by the enantiomer of the chiral tartrate diester usually. This reaction is used to break a double bond and add two hydroxyl groups in a cis manner. Such symmetry is useful in ligand design, furnishing predictable and repetitive structural units which reduce the number of diastereomeric transition states ho oh o ro o or ti o o e ti o. Myers sharpless asymmetric epoxidation reaction chem 115. Epoxidation condensation approaches darzens condensation sulfur ylides with organic peroxides peroxy acids peroxy iminic acids dioxiranes dmdo enantioselective versions metalcatalyzed approaches voacac 2 sharpless ae metal oxos mto fe, pt and mnbased. Sharpless asymmetric dihydroxylation is a stereoselective reaction that is known to be extremely reliable. An asymmetric dihydroxylation reaction was performed using the improved sharpless conditions with the newer aqn based ligands, producing excellent ees for both enantiomers of the diol, 95% for the enantiomer derived from admix. The sharpless epoxidation reaction is an enantioselective chemical reaction to prepare 2,3epoxyalcohols from primary and secondary allylic alcohols. H 2o 2 ch 3cn may also be used as stoichiometic oxidant. Nov 19, 2017 csir net chemical science solved question june 2017,woodward reaction and prevost reaction in hindi duration. Shi asymmetric epoxidation chiral dioxirane strategy. While nmo is also a viable reagent as the reoxidant, the use of potassium ferricyanide. Asymmetric dihydroxylation of 9 with dhqd2phal ligand gave the diol 10 in 93% yield and.
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