The mukaiyama aldol addition is an organic reaction and a type of aldol reaction between a silyl enol ether and an aldehyde catalyzed by a lewis acid. Nov 11, 20 the aldol type reactions of acetals with silicon enolates proceeded smoothly using a catalytic amount of me 3 siotf. Structural variation in the aldehyde donor component has also been examined. Sheng wang hefei national laboratory for physical sciences at the microscale and department of chemistry, university of science and technology of china, hefei, 230026 p. Up to four products are possible two selfaddition and two crossedaddition products.
Pdf mukaiyama aldol reactions in aqueous media researchgate. The doubly diastereoselective aldol reaction of 1 and isobutyraldehyde provided the readily purified crystalline intermediate 2. This choice of reactants allows for a crossed aldol reaction between an aldehyde and a ketone or a different aldehyde without selfcondensation of the aldehyde. A novel approach to the synthesis of optically active poly. Lewis acid can undergo a mukaiyama aldol reaction favoring the formation of the syn 1,5diol with benzaldehyde and fav oring the anti 1,5diol with many other. The first direct and enantioselective crossaldol reaction.
The asymmetric vinylogous mukaiyama aldol reaction. For this reason the reaction is used extensively in organic synthesis. Enantioselective relay catalytic cascade intramolecular. The mukaiyama aldol reaction does not follow the zimmermantraxler model. The mechanism begins by coordination of the aldehydes oxygen to titanium, which activate the carbonyl for attack while also releasing a chloride ion. It was first reported in 1973, and this year marks the 40th anniversary. Study of the lanthanidecatalyzed, aqueous, asymmetric.
N2 the vinylogous mukaiyama aldol reaction vmar is a powerful tool of polyketide synthesis, which constructs a large size structure by simultaneous introduction of the stereogenic centers and the. Sep 17, 2004 specifically, we reasoned that a mukaiyama aldol reaction between an. The diastereoselectivity of a vinylogous mukaiyama aldol reaction of a series of nsubstituted 4oxy2trimethylsilyloxypyrroles with a tartratebased aldehyde has been explored as a model reaction for castanospermine synthesis results. Crossedaldol using preformed enolates if the enolate is preformed and added to the aldehyde, the desired crossedaldol product will be obtained in high yield. In this paper, we describe an optimized ligand synthesis, trends in stereoselectivity that result from. Efficient lewis base for mukaiyama aldol reaction with. The mukaiyama aldol addition is an organic reaction and a type of aldol reaction between a. Four decades since mukaiyamas first reports on the successful application of silicon and boron enolates in directed aldol reactions, the ability of this highly controlled carboncarbon bond. General characteristics acid or basepromoted classical aldol reactions give a complex mixture of products because of the reversibility and the difficulty of controlling the enolate geometry.
A new onepot tandem aldol process is described in which a secondary epoxy silyl ether is converted into the 1,5bissilyloxy3alkanone in good yield. The reaction usually requires only a catalytic amount of lewis acid activator. However, their detailed mechanisms and the role of water molecules remained unclear. Discovered independently by the russian chemist alexander borodin in 1869 and by the french chemist charlesadolphe wurtz in 1872, the reaction combines two carbonyl compounds the original experiments used aldehydes to form a new. Shownin figure 2isan extendedopentransitionstate model, initially proposed by noyori and coworkers. Mukaiyama reaction an overview sciencedirect topics. Mukaiyama aldol reactions of aldehydes with silyl enol ethers are amongst the most widely used lewisacidmediated or catalyzed reactions. When the r groups in one molecule are different than those in the other, the reaction is called a. Diastereoselectivity in lewisacid catalyzed mukaiyama. This lack of stereocontrol is well illustrated by the aldol reaction of chiral silyl enol ether 10, in which the major diastereomer, 11 or 12, depends on the achiral aldehyde scheme 1.
Mixed aldol reactions mixed aldol reactions involve two different carbonyl compounds. Mukaiyama aldol reaction of 6chloro5hydroxypyridinecarbaldehyde with methyl trimethylsilyl ketene acetal occurs in 90% yield and 94% ee in the presence of carreiras binaphthyl ligand tiopr i 4 and 3,5ditertbutylsalicylic acid. Twostep synthesis of carbohydrates by selective aldol reactions. The mukaiyama aldol addition is an organic reaction and a type of aldol reaction between a silyl enol ether and an aldehyde or formate. The asymmetric vinylogous mukaiyama aldol reaction request pdf. Both aldol reaction and aldol condensation are overall reversible. One example is the species generated by mixing trimethylsilyl triflate or chloride and botf 3, 319,320. In order to explore complex potential energy surfaces for the water. Twostep synthesis of carbohydrates by selective aldol. The study has revealed that the reaction is sensitive to the nature of the combination of n and 4oxy substituents. Sep 12, 2012 while many aldol reactions and their stereoselectivity have been studied extensively using computational methods, 2234 only two quantummechanical studies of the lewisacid catalyzed mukaiyama aldol reaction have been published to date. Find, read and cite all the research you need on researchgate. Myers stereoselective, directed aldol reaction chem 115.
Mukaiyamaaldol reaction silyl enol ethers as an enolate precursors. The first direct and enantioselective crossaldol reaction of aldehydes alan b. We have developed a new series of chiral lanthanidecontaining complexes that produce mukaiyama aldol products with outstanding enantioselectivities. Asymmetric mukaiyama aldol reaction by addition of silyl enol derivatives 2 to aldehydes 3 catalyzed by chiral bisoxazoline box catalysts like 1, 5. The aldoltype reactions of acetals with silicon enolates proceeded smoothly using a catalytic amount of me 3 siotf. His choice of reactants allows for a crossed aldol reaction between an aldehyde and a ketone or a different aldehyde without selfcondensation of the aldehyde. Aldol addition aldol reaction aldol is an abbreviation of aldehyde and alcohol.
An enantioselective mukaiyama aldol reaction catalyzed by a tryptophan. The reaction mechanism of the mukaiyama aldol reaction variations of the mukaiyama aldol reaction are so diverse that it is difficult to explain the mechanism with a single model. Results the study has revealed that the reaction is sensitive to the nature of the combination of n and 4oxy. Mechanism of mof505 and cuzsm5 promoted mukaiyama aldol. Consequently, if an aldol, the product of aldol reaction, or an. Only one case of a mukaiyama aldol reaction using tmsotf and benzaldehyde has been reported,4 while in all other cases the aldehyde was activated as an acetal derivative. Jun 14, 2012 the development of efficient methods for the asymmetric mukaiyama aldol reaction in aqueous solution has received great attention. The open transition state is preferred, but the outcome of the reaction synanti depends on the size of substituents and on the lewis acid. The vinylogous mukaiyama aldol reaction vmar allows efficient access to larger segments for complex natural product synthesis, primarily polyketides, through the construction of vicinal hydroxyl and methyl groups as well as. The development of efficient methods for the asymmetric mukaiyama aldol reaction in aqueous solution has received great attention.
Enantioselective relay catalytic cascade intramolecular hydrosiloxylation and mukaiyama aldol reaction pu. Thus, treatment of the epoxy silyl ether 8 with tbsotf and base affords the silyl enol ether 9 via non aldol aldol rearrangement and addition of benzaldehyde and tbsotf gives the ketone 10 with 4. The open transition state is preferred, but the outcome of the reaction synanti depends on the size of substituents. Professor mukaiyama has also investigated dehydration reactions, which are very important and fundamental reactions in organic synthesis. Aldol condensation can occur between two identical or different aldehydes two identical or different ketones an aldehyde and a ketone 10. The synthesis features an abikomasamune aldol reaction, a vinylogous mukaiyama aldol reaction, and a macrocyclization involving an acyl ketene intermediate for the construction of the macrocyclic. Mukaiyama aldol reaction article about mukaiyama aldol. Mukaiyama aldol addition wikipedia republished wiki 2. Lewis bases such as fluoride anion can also work as the activator of silyl enol ethers. Nheterocyclic carbenes were shown to be highly effective catalysts to promote mukaiyama aldol reactions. The mukaiyama aldol reaction is the nucleophilic addition of silyl enol ethers to aldehydes catalyzed by a lewis acid such as boron trifluoride as boron trifluoride etherate or titanium tetrachloride. The vinylogous mukaiyama aldol reaction vmar in natural. Here we dont have two aldehydes that are the same, we have different aldehydes.
The relative and absolute stereochemistry of a representative product was rigorously assigned by nmr and cd spectroscopies measured and calculated, x. Mechanism, references and reaction samples of the mukaiyama aldol addition. Macmillan division of chemistry and chemical engineering, california institute of technology, pasadena, california 91125 received march 19, 2002 over. Lewis acid promoted condensation of silyl ketene acetals ester enolate equiv. We were able to obtain the desired aldol product 10 favoring the syn 1,5diol with benzaldehyde and catalytic amounts of tbsotf scheme 3. Catalytic enantioselective vars leading references. In the previous video we looked at aldol condensations with the same molecule, you call those a simple aldol condensation.
Jul 15, 2005 the aldol reaction, usually carried out in protic solvents with base or acid as the catalyst, is one of the most versatile methods in organic synthesis. Catalyzed vinylogous mukaiyama aldol reactions with. The impact of the mukaiyama aldol reaction in total. T1 recent development of vinylogous mukaiyama aldol reactions. However, trimethylsilyl triflate is not active enough to promote these reactions, 66 and more active siliconbased lewis acids have been developed. The aldol reaction was discovered by aleksandr por.
The trimethylsilyl group is thought of as a sterically demanding hydrogen equivalent that activates the enol and traps the aldol hydroxyl. Mukaiyama aldol addition an overview sciencedirect topics. The two illustrated stransition states do not differ significantly in energy, but there is a prevalent view that the antiperiplanar transition state is favored based on electrostatic effects. The main advantages in the mukaiyama approach are the chemoselectivity of the reaction and the possibility of stereoselective execution. New modified protocols allow syn or antiselective transformations and even the selective preparation of enantiomers.
Diastereoselection in lewisacidmediated aldol additions. The reaction was discovered by teruaki mukaiyama born 1927 in 1973. Nheterocyclic carbenecatalyzed mukaiyama aldol reactions. By application of this reaction a great number of aldols and related compounds have been prepared from various carbonyl compounds. Specifically, we reasoned that a mukaiyama aldol reaction between an. Carreira has described particularly useful asymmetric methodology. Jul 26, 20 four decades since mukaiyamas first reports on the successful application of silicon and boron enolates in directed aldol reactions, the ability of this highly controlled carboncarbon bond. Aldol reaction under conditions where enolate formation is reversible, a complex mixture results. All content on this website, including dictionary, thesaurus, literature, geography, and other reference data is for informational purposes only. The reaction is catalyzed more commonly by a base or some times by an acid. His choice of reactants allows for a crossed aldol reaction between an aldehyde and a ketone or a different aldehyde without self. Request pdf mukaiyama aldol reaction lewis acidcatalyzed aldol condensation of aldehyde and silyl enol ether. In the 1970s, mukaiyamas group developed the crossed aldol reactions using.
The mukaiyama aldol reaction proceeds through an open transition state, which can be represented in a newman projection. Mixed crossed aldol condensation video khan academy. Aldol reaction wikipedia mukaiyama aldol addition wikipedia. Carboncarbon bond formations, such as kobayashi modification of the mukaiyamaaldol reaction, catalyzed by lanthanide ln lewis acid in aqueous solution comprise one of the most attractive types of reactions in terms of green chemistry. Recent development of vinylogous mukaiyama aldol reactions. Zimmerman and traxler proposed that the aldol reaction with metal enolates. The mukaiyama aldol reaction was first extended to catalytic versions and then to catalytic asymmetric versions, and many research groups have actively pursued applications of this methodology. The aldol reaction is a means of forming carboncarbon bonds in organic chemistry. Organic letters a tandem nonaldol aldol mukaiyama aldol reaction. The mukaiyama reaction is extremely useful on a lab scale and has been used in numerous complex molecule syntheses. The first direct and enantioselective crossaldol reaction of. Aldol condensation aldol addition mukaiyama aldol addition the aldol condensation of aldehyde.
The aldol addition reaction involves the addition of. The use of silyl enol ethers as an enolate equivalent in lewis acidcatalyzed aldol additions. The mukaiyama aldol addition is an organic reaction used to convert an aldehyde and a silyl enol ether to a 1,3 ketol using a lewis acid catalyst such as ticl 4, followed by aqueous workup. In this paper, we describe an optimized ligand synthesis, trends in stereoselectivity that result from changing. The impact of the mukaiyama aldol reaction in total synthesis. The mukaiyama aldol reaction, an acidcatalyzed aldol reaction between a silyl enol ether and a carbonyl compound, has been an important and versatile tool in organic and biochemical domains 1.
Diastereoselectivity in lewisacid catalyzed mukaiyama aldol. A new catalytic vinylogous mukaiyama aldol reaction provides products with high diastereo. The mukaiyama aldol addition is an organic reaction used to convert an aldehyde and a silyl enol ether to a 1,3 ketol using a lewis acid catalyst such as ticl4. Mukaiyama aldol reaction themukaiyamaaldolreaction. Ishihara and coworkers recently reported the lewis basecatalyzed mukaiyama aldol reaction using a simple mixed sodium phenoxidephosphine oxide catalyst. In this video were going to look at mixed or crossed aldol condensations, so no longer are you starting with the same molecule. With some significant exceptions, enolsilanes are unreactive toward aldehydes. The diastereoselectivity of a vinylogous mukaiyama aldol reaction of a series of nsubstituted 4oxy2trimethylsilyloxypyrroles with a tartratebased aldehyde has been explored as a model reaction for castanospermine synthesis. Aldol condensation from the addition of silyl enol ethers and silyl ketene. The aldol reaction, usually carried out in protic solvents with base or acid as the catalyst, is one of the most versatile methods in organic synthesis. While many aldol reactions and their stereoselectivity have been studied extensively using computational methods, 2234 only two quantummechanical studies of the lewisacid catalyzed mukaiyama aldol reaction have been published to date. As revealed in entries 57, this cross aldol reaction can.
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