NationMaster - Encyclopedia: Aldol reaction

The aldol reaction is an important carbon-carbon bond forming reaction in organic chemistry^[1] ^[2] ^[3] involving the addition of an enol or enolate anion to an aldehyde or ketone.^[4] ^[5] ^[6] The initial reaction product is a β-hydroxy ketone (or aldehyde), also called an "aldol" (aldehyde + alcohol), and this reaction is called aldol addition. The initial aldol adduct can subsequently lose a molecule of water to form an α,β-unsaturated ketone (or aldehyde). This is called aldol condensation. Image File history File linksMetadata Aldolrxnpic. ... Image File history File linksMetadata Aldolrxnpic. ... A carbon-carbon bond is a covalent bond between two carbon atoms - a single bond is composed of two electrons, one from each of the two atoms. ... Organic reactions are chemical reactions between organic compounds. ... Organic chemistry is a specific discipline within the subject of chemistry. ... Enol (or, more officially, but less commonly: alkenol) is an alkene with hydroxyl group on one of the carbon atoms of the double bond. ... Enol (or, more officially, but less commonly: alkenol) is an alkene with hydroxyl group on one of the carbon atoms of the double bond. ... An aldehyde. ... Ketone group A ketone is either the functional group characterized by a carbonyl group linked to two other carbon atoms or a chemical compound that contains this functional group. ... Ketone group A ketone is either the functional group characterized by a carbonyl group linked to two other carbon atoms or a chemical compound that contains this functional group. ... An aldehyde. ... In chemistry, a dehydration reaction is a chemical reaction that involves the loss of water from the reacting molecule. ... In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom. ... An Aldol condensation is an organic reaction where an enolate ion reacts with a carbonyl compound to form a Î²-hydroxyaldehyde or Î²-hydroxyketone followed by dehydration to a conjugated enone. ...

The enol or enolate is itself generated from a carbonyl compound, often an aldehyde or ketone, using acid or base. If the enol or enolate is formed in situ, the process can be considered as an acid or base-catalyzed reaction of one carbonyl compound with another. This may involve one aldehyde or ketone reacting with itself. Alternatively two different carbonyl compounds may be used, in which case the reaction is known as a crossed aldol reaction. In chemistry, a carbonyl group is a functional group composed of an atom of carbon double-bonded to an atom of oxygen. ... In situ is a Latin phrase meaning in the place. ...

In 1872, the aldol reaction was discovered independently by Charles-Adolphe Wurtz ^[7] and by Alexander Porfyrevich Borodin. Borodin observed the formation of 3-hydroxybutanal from acetaldehyde under acidic conditions. 1872 (MDCCCLXXII) was a leap year starting on Monday (see link for calendar) of the Gregorian calendar or a leap year starting on Wednesday of the 12-day-slower Julian calendar. ... Charles Adolphe Wurtz (November 26, 1817 - May 10, 1884) was a French chemist. ... Portrait of Borodin Alexander Porfirevich Borodin (ÐÐ»ÐµÐºÑÐ°Ð½Ð´Ñ€ ÐŸÐ¾Ñ€Ñ„Ð¸Ñ€ÑŒÐµÐ²Ð¸Ñ‡ Ð‘Ð¾Ñ€Ð¾Ð´Ð¸Ð½ in Cyrillic, Aleksandr PorfireviÄ Borodin in transliteration) (31 Oct. ... R-phrases , , S-phrases , , , Flash point âˆ’39 Â°C Autoignition temperature 185 Â°C RTECS number AB1925000 Supplementary data page Structure and properties n, Îµr, etc. ...

Mechanisms

If an aldehyde or ketone is converted to an enol or enolate, it becomes nucleophilic at the α-carbon. α,β-Unsaturated aldehydes or ketones can also be deprotonated to form vinylogous enolates.^[8] This allows it to attack an electrophilic component (a carbonyl or protonated carbonyl) to form the aldol. The aldol reaction may proceed under acidic or basic conditions, as shown above. If specific acid catalysis is used, the reaction involves a weak nucleophile (an enol) attacking a strong electrophile (the protonated carbonyl). Under basic conditions, a nucleophile (the enolate) is formed which is strong enough to react with the unprotonated carbonyl. Dehydration may or may not occur, depending on the conditions. If strong base and kinetic control (see below) are used, the intermediates do not equilibrate and the reaction becomes in effect irreversible. In chemistry, a nucleophile (literally nucleus lover) is a reagent which is attracted to centres of positive charge. ... The Alpha carbon refers to the first carbon after the carbon that attaches to the functional group. ... Deprotonation is a chemistry term that refers to the removal of a proton (hydrogen ion H+) from a molecule, forming the conjugate base. ... Vinyl products (such as these records) come in many colors. ... In chemistry, an electrophile (literally electron-lover) is a reagent attracted to electrons that participates in a chemical reaction by accepting an electron pair in order to bond to a nucleophile. ... For alternative meanings see acid (disambiguation). ... A bases in chemistry is a chemical substance which has a free pair of electrons to bind a Hydrogen ion commonly referred to as a proton (IUPAC definition). ... In acid catalysis and base catalysis a chemical reaction is catalyzed by an acid or a base. ... Protonation is the addition of a proton (H+) to an atom, molecule, or ion. ... Chemical equilibrium is the state in which the concentrations of the reactants and products have no net change over time. ...

Image File history File links Download high resolution version (999x407, 62 KB) Summary A simple overview of the aldol reaction including the aldol condensation. ...

Enol mechanism

When an acid catalyst is used, the initial step in the reaction mechanism involves acid-catalyzed tautomerization of the carbonyl compound to the enol. The acid also serves to activate the carbonyl group of another molecule by protonation, rendering it highly electrophilic. The enol is nucleophilic at the α-carbon, allowing it to attack the protonated carbonyl compound, leading to the aldol after deprotonation. This usually dehydrates to give the unsaturated carbonyl compound. The scheme shows a typical acid-catalyzed self-condensation of an aldehyde.

In chemistry, a reaction mechanism is the step by step sequence of elementary reactions by which overall chemical change occurs. ... Tautomers are organic compounds that are interconvertible by a chemical reaction called tautomerization. ... In chemistry, an electrophile (literally electron-lover) is a reagent attracted to electrons that participates in a chemical reaction by accepting an electron pair in order to bond to a nucleophile. ... In chemistry, a nucleophile (literally nucleus lover) is a reagent which is attracted to centres of positive charge. ... Deprotonation is a chemistry term that refers to the removal of a proton (hydrogen ion H+) from a molecule, forming the conjugate base. ... Image File history File links Enol_aldol_mechanism. ...

Enolate mechanism

If the catalyst is a moderate base such as hydroxide ion or an alkoxide, the aldol reaction occurs via nucleophilic attack by the resonance-stabilized enolate on the carbonyl group of another molecule. The product is the alkoxide salt of the aldol product. The aldol itself is then formed, and it may then undergo dehydration to give the unsaturated carbonyl compound. The scheme shows a simple mechanism for the base catalyzed aldol reaction of an aldehyde with itself. It has been suggested that this article or section be merged into Catalysis. ... Hydroxide is a polyatomic ion consisting of oxygen and hydrogen: OHâˆ’ It has a charge of âˆ’1. ... An alkoxide has an organic group bonded to a negatively charged oxygen atom, they are generally basic. ... Resonance structures of Benzene Resonance structures are diagrammatic tools used predominately in organic chemistry to symbolize resonant bonds between atoms in molecules. ... An alkoxide has an organic group bonded to a negatively charged oxygen atom, they are generally basic. ...

If a stronger base such as LDA or NaHMDS is used in stoichiometric amounts, the formation of the enolate becomes irreversible, and this helps to drive the reaction forward. In such cases the aldol product is not formed until a separate protonation step is performed. Otherwise, the mechanism can be regarded as the same. The chemical compound sodium bis(trimethylsilyl)amide is a strong base used for deprotonation reactions or base catalyzed reaction. ... In chemistry, stoichiometry is the study of the combination of elements in chemical reactions. ...

More refined forms of the mechanism are known. In 1957, Zimmerman and Traxler proposed that some aldol reactions have "six-membered transition state[s] having a chair conformation".^[9] This has become known as the Zimmerman-Traxler model. E-enolates give rise to anti products, whereas Z-enolates give rise to syn products.^[10] E and Z refer to the cis-trans stereochemical relationship between the enolate oxygen bearing the positive counterion and the highest priority group on the alpha carbon. In reality, only some metals such as lithium and boron reliably follow the Zimmerman-Traxler model, with the result that the stereochemical outcome of the reaction may be unpredictable. Ethylene undergoing syn and anti addition In organic chemistry, anti addition is the addition of two substituents to opposite sides (or faces) of a double bond or triple bond, resulting in a decrease in bond order but an increase in number of substituents. ... Ethylene undergoing syn and anti addition In organic chemistry, syn addition is the addition of two substituents to the same side (or face) of a double bond or triple bond, resulting in a decrease in bond order but an increase in number of substituents. ... Cis-2-butene Trans-2-butene In chemistry, geometric isomerism or cis-trans isomerism is a form of stereoisomerism and describes the orientation of functional groups at the ends of a bond around which no rotation is possible. ...

Control in the Aldol reaction

The problem

The problem of "control" in the aldol addition is best demonstrated by an example. Consider the outcome of this hypothetical reaction:

In this reaction, two unsymmetrical ketones are being condensed using sodium ethoxide. The basicity of sodium ethoxide is such that it cannot fully deprotonate either of the ketones, but can produce small amounts of the sodium enolate of both ketones. Effectively, this means that in addition to being potential aldol electrophiles, both ketones may also act as nucleophiles via their sodium enolate. Two electrophiles and two nucleophiles then potentially results in four possible products: Image File history File links Aldolcontrol1. ... In chemistry, the alkoxyl group is an alkyl group linked to oxygen thus: R-O- In this function, R represents the alkyl group. ...

Thus, if one wishes to obtain only one of the cross-products, then one must "control" the aldol addition. Image File history File links Aldolcontrol2. ...

Acidity

If one partner is considerably more acidic than the other, then control may be automatic. For example, the addition of diethyl malonate into benzaldehyde would not be problematic:

In this case, the doubly activated methylene protons of the malonate would be preferentially deprotonated by sodium ethoxide and quantitatively form the sodium enolate. Since benzaldehyde has no acidic alpha-protons, there is only one possible nucleophile-electrophile combination; hence, control has been achieved. Note that this approach combines two elements of control: increased acidity of the alpha protons on the nucleophile and the lack of alpha protons on the electrophile. Image File history File links Aldolcontrol3. ... In chemistry, methylene is a divalent functional group CH2 derived formally from methane. ... The malonate or propanedioate ion is CH2(COO)22âˆ’ (malonic acid minus two hydrogen ions). ... The chemical compound benzaldehyde (C6H5CHO) consists of a benzene ring with an aldehyde group attached to one carbon. ...

Order of addition

One common solution is to form the enolate of one partner first, and then add the other partner under kinetic control ^[11]. Kinetic control means that the forward aldol addition reaction must be significantly faster than the reverse retro-aldol reaction. For this approach to succeed, two other conditions must also be satisfied; namely, it must be possible to quantitatively form the enolate of one partner and the forward aldol reaction must be significantly faster than the transfer of the enolate from one partner to another. Common kinetic control conditions involve the formation of the enolate of a ketone with LDA at -78 °C, followed by the slow addition of an aldehyde. Thermodynamic reaction control or kinetic reaction control in a chemical reaction can decide the composition in a reaction product when competing reactions lead to different products under different reaction conditions. ... LDA may stand for: Low density amorphous ice, a form of amorphous ice Lithium diisopropylamide Linear discriminant analysis statistics Local-density approximation quantum_mechanics London Development Agency This page concerning a three-letter acronym or abbreviation is a disambiguation page â€” a navigational aid which lists other pages that might otherwise share...

Enolates

Formation

Enolization may be effected using a strong base ("hard conditions") or using a Lewis acid and a weak base ("soft conditions"): In chemistry, a Lewis acid can accept a pair of electrons and form a coordinate covalent bond, after the American chemist Gilbert Lewis. ...

For deprotonation to occur, the stereoelectronic requirement is that the alpha-C-H sigma bond must be able to overlap with the pi* orbital of the carbonyl: Deprotonation is a chemistry term that refers to the removal of a proton (hydrogen ion H+) from a molecule, forming the conjugate base. ... Electron atomic and molecular orbitals, showing among others the sigma bond of two s-orbitals and a sigma bond of two p-orbitals In chemistry, sigma bonds (Ïƒ bonds) are a type of covalent chemical bond. ... Carbonyl group In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom. ...

Geometry

Extensive studies have been performed on the formation of enolates under many different conditions. It is now possible to generate, in most cases, the desired enolate geometry:^[12]

For ketones, most enolization conditions give Z enolates. For esters, most enolization conditions give E enolates. The addition of HMPA is known to reverse the stereoselectivity of deprotonation. Image File history File links Scheme3. ... General formula of a carboxylate ester. ... HMPA is commonly known in chemists circles as liquid cancer. It is used to improve the stereoselectivity of certain reactions; although it used to be used as a bulk solvent, due to its severe carcinogenicity, it is currently used as an additive; luckily its selectivity-enhancing properties are preserved... In chemistry, a stereoselectivity is the property of a chemical reaction that yields an unequal mixture of stereoisomers from a single reactant. ...

The stereoselective formation of enolates has been rationalized with the so-called Ireland model,^[13] ^[14] ^[15] ^[16] although its validity is somewhat questionable. In most cases, it is not known which, if any, intermediates are monomeric or oligomeric in nature; nonetheless, the Ireland model remains a useful tool for understanding enolates. Image File history File links Scheme3b. ... In chemistry, a monomer (from Greek mono one and meros part) is a small molecule that may become chemically bonded to other monomers to form a polymer. ... In chemistry, an oligomer consists of a finite number of monomer units (oligo is Greek for a few), in contrast to a polymer which, at least in principle, consists of an infinite number of monomers. ...

Kinetic vs. thermodynamic enolates

If an unsymmetrical ketone is subjected to base, it has the potential to form two regioisomeric enolates (ignoring enolate geometry). For example:

The trisubstituted enolate is considered the kinetic enolate while the tetrasubstitued enolate is considered the thermodynamic enolate. The alpha hydrogen deprotonated to form the kinetic enolate is less hindered, and therefore deprotonated more quickly. In general, tetrasubstituted olefins are more stable than trisubstituted olefins due to hyperconjugative stabilization. The ratio of enolate regioisomers is heavily influenced by the choice of base. For the above example, kinetic control may be established with LDA at -78°C, giving 99:1 selectivity of kinetic:thermodynamic enolate, while thermodynamic control may be established with triphenylmethyllithium at room temperature, giving 10:90 selectivity. Image File history File links Enolateregio1. ... Thermodynamic reaction control or kinetic reaction control in a chemical reaction can decide the composition in a reaction product when competing reactions lead to different products under different reaction conditions. ... An organolithium reagent is an organometallic compound with a direct bond between a carbon and a lithium atom. ... To meet Wikipedias quality standards, this article may require cleanup. ...

In general, kinetic enolates are favored by cold temperatures, relatively ionic metal-oxygen bonds, and rapid deprotonation using a slight excess of a strong, hindered base while thermodynamic enolates are favored by higher temperatures, relatively covalent metal-oxygen bonds, and longer equilibration times for deprotonation using a slight sub-stoichiometric amount of strong base. Use of a sub-stoichiometric amount of base allows some small fraction of unenolized carbonyl compound to equilibrate the enolate to the thermodynamic regioisomer by acting as a proton shuttle.

Stereoselectivity

E vs. Z enolates

There is no significant difference between the level of stereoinduction observed with E and Z enolates:^[17] Asymmetric induction in stereochemistry describes the preferential formation in a chemical reaction of one enantiomer or diastereoisomer over the other as a result of the influence of a chiral feature present in the substrate, reagent, catalyst or environment [1]. Asymmetric induction is a key element in asymmetric synthesis. ...

Image File history File links EvsZstereoselectivity. ... Image File history File links EvsZstereoselectivity2. ...

Metal ion

The enolate metal cation may play a large role in determining the level of stereoselectivity in the aldol reaction. Boron is often used because its bond lengths are significantly shorter than that of other metals such as lithium, aluminum, or magnesium. For example, boron-carbon and boron-oxygen bonds are 1.4-1.5 Å and 1.5-1.6 Å in length, respectively, whereas typical metal-carbon and metal-oxygen bonds are typically 1.9-2.2 Å and 2.0-2.2 Å in length, respectively. This has the effect of "tightening" the transition state:^[18] General Name, Symbol, Number boron, B, 5 Chemical series metalloids Group, Period, Block 13, 2, p Appearance black/brown Atomic mass 10. ... In molecular geometry, bond length or bond distance is the distance between two bonded atoms in a molecule. ... General Name, Symbol, Number lithium, Li, 3 Chemical series alkali metals Group, Period, Block 1, 2, s Appearance silvery white/grey Atomic mass 6. ... Aluminum is a soft and lightweight metal with a dull silvery appearance, due to a thin layer of oxidation that forms quickly when it is exposed to air. ... General Name, Symbol, Number magnesium, Mg, 12 Chemical series alkaline earth metals Group, Period, Block 2, 3, s Appearance silvery white Atomic mass 24. ... An angstrom, angstrÃ¶m, or Ã¥ngstrÃ¶m (symbol Ã…) is a unit of length. ... The transition state of a chemical reaction is a particular configuration along the reaction coordinate. ...

Stereoselectivity: Alpha stereocenter on the enolate

The aldol reaction may exhibit "substrate-based stereocontrol", in which existing chirality on either reactant influences the sterochemical outcome of the reaction. This has been extensively studied, and in many cases, one can predict the sense of asymmetric induction, if not the absolute level of diastereoselectivity. If the enolate contains a stereocenter in the alpha position, excellent stereocontrol may be realized. The term chiral (pronounced ) is used to describe an object which is non-superimposable on its mirror image. ... Asymmetric induction in stereochemistry describes the preferential formation in a chemical reaction of one enantiomer or diastereoisomer over the other as a result of the influence of a chiral feature present in the substrate, reagent, catalyst or environment [1]. Asymmetric induction is a key element in asymmetric synthesis. ... Diastereomers are stereoisomers that are not enantiomers or mirror images of each other. ... A stereocenter in organic chemistry generally refers to a carbon atom in a chemical compound that has four different types of atoms or groups of atoms attached to it. ...

In the case of an E enolate, the dominant control element is allylic 1,3-strain whereas in the case of a Z enolate, the dominant control element is the avoidance of 1,3-diaxial interactions. The general model is presented below: Image File history File links Enolatealphacenter. ... Allylic strain or 1,3-allylic strain in organic chemistry and its associated strain energy results from an unfavorable molecular conformation for the allyl group. ...

For clarity, the stereocenter on the enolate has been epimerized; in reality, the opposite diastereoface of the aldehyde would have be attacked. In both cases, the 1,3-syn diastereomer is favored. There are many examples of this type of stereocontrol:^[19] Image File history File links Enolatealphacentermodel. ... In chemistry, an epimer is a stereoisomer that has a different configuration at only one of several stereogenic centers. ...

Stereoselectivity: Alpha stereocenter on the electrophile

When enolates attacks aldehydes with an alpha stereocenter, excellent stereocontrol is also possible. The general observation is that E enolates exhibit Felkin diastereoface selection, while Z enolates exhibit anti-Felkin selectivity. The general model^[20]^[21] is presented below: Asymmetric induction in stereochemistry describes the preferential formation in a chemical reaction of one enantiomer or diastereoisomer over the other as a result of the influence of a chiral feature present in the substrate, reagent, catalyst or environment [1]. Asymmetric induction is a key element in asymmetric synthesis. ...

Since Z enolates must react through a transition state which either contains a destabilizing syn-pentane interaction or anti-Felkin rotamer, Z-enolates exhibit lower levels of diastereoselectivity in this case. Some examples are presented below:^[22]^[23] Image File history File links Aldehydealphamodel. ... The transition state of a chemical reaction is a particular configuration along the reaction coordinate. ... In chemistry, a chemical conformation is the spatial arrangement of atoms in a molecule. ...

Stereoselectivity: Merged model for stereoinduction

If both the enolate and the aldehyde both contain pre-existing chirality, then the outcome of the "double stereodifferentiating" aldol reaction may be predicted using a merged stereochemical model that takes into account the enolate facial bias, enolate geometry, and aldehyde facial bias.^[24] Several examples of the application of this model are given below:^[25]

Asymmetric aldol reaction

Modern organic syntheses now require the synthesis of compounds in enantiopure form. Since the aldol addition reaction creates two new stereocenters, up to four stereoisomers may result. In chemistry two stereoisomers are said to be enantiomers if one can be superimposed on the mirror image of the other. ...

Many methods which control both relative stereochemistry (i.e., syn or anti, as discussed above) and absolute stereochemistry (i.e., R or S) have been developed. Image File history File links Evansaldol1. ... The different types of isomers. ...

Evans' oxazolidone chemistry

A widely used method is the Evans' acyl oxazolidinone method.^[26]^[27] Developed in the late 1970s and 1980s by David A. Evans and coworkers, the method works by temporarily creating a chiral enolate by appending a chiral auxiliary. The pre-existing chirality from the auxiliary is then transferred to the aldol adduct by performing a diastereoselective aldol reaction. Upon subsequent removal of the auxiliary, the desired aldol stereoisomer is revealed. In chemistry, the terms acyl or acyl group refer to a functional group obtained from an acid by removal of a hydroxyl group. ... Oxazolidinones are the last generation of antibiotics used against gram-positive pathogens, including superbugs such as Staphylococcus aureus. ... The 1970s decade refers to the years from 1970 to 1979, inclusive. ... The examples and perspective in this article or section may not represent a worldwide view. ... David A. Evans (b. ... A chiral auxiliary is a chemical compound or unit that is temporarily incorporated into a organic synthesis so that it can be carried out asymmetrically with the selective formation of one of twoenantiomers. ...

In the case of the Evans' method, the chiral auxiliary appended is an oxazolidinone, and the resulting carbonyl compound is an imide. A number of oxazolidinones are now readily available in both enantiomeric forms. These may cost roughly $10-$20 US dollars per gram, rendering them relatively expensive. Image File history File links Evansaldol3. ... Oxazolidinones are the last generation of antibiotics used against gram-positive pathogens, including superbugs such as Staphylococcus aureus. ... In organic chemistry, imide is a functional group consisting of two carboxylic acid groups (or one dicarboxylic acid) bound to a primary amine or ammonia. ...

The acylation of an oxazolidinone is a convenient procedure, and is informally referred to as "loading done". Z-enolates, leading to syn-aldol adducts, can be reliably formed using boron-mediated soft enolization:^[28] Image File history File links Evansaldol4. ... In chemistry, acylation is the process of adding an acyl group to a compound. ...

Often, a single diastereomer may be obtained by one crystallization of the aldol adduct. Unfortunately, anti-aldol adducts cannot be obtained reliably with the Evans method. Despite the cost and being limited to syn adducts, the method's superior reliability, ease of use, and versatility render it the method of choice in many situations. Many methods are available for the cleavage of the auxiliary:^[29] Image File history File links Evansaldol5. ... Diastereomers are stereoisomers that are not enantiomers, or mirror images of each other. ... Crystal (disambiguation) Insulin crystals A crystal is a solid in which the constituent atoms, molecules, or ions are packed in a regularly ordered, repeating pattern extending in all three spatial dimensions. ...

Upon construction of the imide, both syn and anti-selective aldol addition reactions may be performed, allowing the assemblage of three of the four possible stereoarrays: syn selective: ^[30] and anti selective: ^[31] Image File history File links Evansaldol6. ...

In the syn-selective reactions, both enolization methods give the Z enolate, as expected; however, the stereochemical outcome of the reaction is controlled by the methyl stereocenter, rather than the chirality of the oxazolidinone. The methods described allow the synthesis of extensive polyketide stereoarrays to be assembled. Image File history File links Evansaldol7. ... Polyketides are secondary metabolites from bacteria, fungi, plants, and animals. ...

References

Clayton Heathcock is an organic chemist, Professor of Chemistry, and Dean of the College of Chemistry at the University of California, Berkeley. ... Chemical Reviews (usually abbreviated as ), is a peer-reviewed scientific journal, published since 1900 by the American Chemical Society. ... A digital object identifier (or DOI) is a permanent identifier (permalink) given to a World Wide Web file or other Internet document so that if its Internet address changes, users will be redirected to its new address. ... The Journal of the American Chemical Society (usually abbreviated as , or JACS), is a peer-reviewed scientific journal, published since 1879 by the American Chemical Society. ... A digital object identifier (or DOI) is a permanent identifier (permalink) given to a World Wide Web file or other Internet document so that if its Internet address changes, users will be redirected to its new address. ... The Journal of Organic Chemistry (abbreviated as ) is a scientific journal for original contributions of fundamental research in organic and bioorganic chemistry. ... Organic Syntheses is a scientific journal that since 1921 has provided the chemistry community with annual collections of detailed and checked procedures for the organic synthesis of organic compounds. ... The Journal of the American Chemical Society (usually abbreviated as , or JACS), is a peer-reviewed scientific journal, published since 1879 by the American Chemical Society. ... A digital object identifier (or DOI) is a permanent identifier (permalink) given to a World Wide Web file or other Internet document so that if its Internet address changes, users will be redirected to its new address. ... Tetrahedron Letters is a weekly international journal for rapid publication of full origonal research papers in the field of organic chemistry. ... Tetrahedron Letters is a weekly international journal for rapid publication of full origonal research papers in the field of organic chemistry. ... The Journal of Organic Chemistry (abbreviated as ) is a scientific journal for original contributions of fundamental research in organic and bioorganic chemistry. ... A digital object identifier (or DOI) is a permanent identifier (permalink) given to a World Wide Web file or other Internet document so that if its Internet address changes, users will be redirected to its new address. ... The Journal of Organic Chemistry (abbreviated as ) is a scientific journal for original contributions of fundamental research in organic and bioorganic chemistry. ... The Journal of the American Chemical Society (usually abbreviated as , or JACS), is a peer-reviewed scientific journal, published since 1879 by the American Chemical Society. ... A digital object identifier (or DOI) is a permanent identifier (permalink) given to a World Wide Web file or other Internet document so that if its Internet address changes, users will be redirected to its new address. ... The Journal of the American Chemical Society (usually abbreviated as , or JACS), is a peer-reviewed scientific journal, published since 1879 by the American Chemical Society. ... A digital object identifier (or DOI) is a permanent identifier (permalink) given to a World Wide Web file or other Internet document so that if its Internet address changes, users will be redirected to its new address. ... The Journal of the American Chemical Society (usually abbreviated as , or JACS), is a peer-reviewed scientific journal, published since 1879 by the American Chemical Society. ... A digital object identifier (or DOI) is a permanent identifier (permalink) given to a World Wide Web file or other Internet document so that if its Internet address changes, users will be redirected to its new address. ... The Journal of Organic Chemistry (abbreviated as ) is a scientific journal for original contributions of fundamental research in organic and bioorganic chemistry. ... A digital object identifier (or DOI) is a permanent identifier (permalink) given to a World Wide Web file or other Internet document so that if its Internet address changes, users will be redirected to its new address. ... The Journal of the American Chemical Society (usually abbreviated as , or JACS), is a peer-reviewed scientific journal, published since 1879 by the American Chemical Society. ... A digital object identifier (or DOI) is a permanent identifier (permalink) given to a World Wide Web file or other Internet document so that if its Internet address changes, users will be redirected to its new address. ... The Journal of the American Chemical Society (usually abbreviated as , or JACS), is a peer-reviewed scientific journal, published since 1879 by the American Chemical Society. ... Angewandte Chemie or Angewandte Chemie International Edition is the chemistry journal of the Gesellschaft Deutscher Chemiker (Society of German Chemists). ... The Journal of the American Chemical Society (usually abbreviated as , or JACS), is a peer-reviewed scientific journal, published since 1879 by the American Chemical Society. ... A digital object identifier (or DOI) is a permanent identifier (permalink) given to a World Wide Web file or other Internet document so that if its Internet address changes, users will be redirected to its new address. ... Organic Syntheses is a scientific journal that Since 1921 has provided the chemistry community with annual collections of detailed and checked procedures for the organic synthesis of organic compounds. ... The Journal of the American Chemical Society (usually abbreviated as , or JACS), is a peer-reviewed scientific journal, published since 1879 by the American Chemical Society. ... A digital object identifier (or DOI) is a permanent identifier (permalink) given to a World Wide Web file or other Internet document so that if its Internet address changes, users will be redirected to its new address. ... The Journal of the American Chemical Society (usually abbreviated as , or JACS), is a peer-reviewed scientific journal, published since 1879 by the American Chemical Society. ... A digital object identifier (or DOI) is a permanent identifier (permalink) given to a World Wide Web file or other Internet document so that if its Internet address changes, users will be redirected to its new address. ... The Journal of the American Chemical Society (usually abbreviated as , or JACS), is a peer-reviewed scientific journal, published since 1879 by the American Chemical Society. ... A digital object identifier (or DOI) is a permanent identifier (permalink) given to a World Wide Web file or other Internet document so that if its Internet address changes, users will be redirected to its new address. ...

Contents

Mechanisms

Enol mechanism

Enolate mechanism

Control in the Aldol reaction

The problem

Acidity

Order of addition

Enolates

Formation

Geometry

Kinetic vs. thermodynamic enolates

Stereoselectivity

E vs. Z enolates

Metal ion

Stereoselectivity: Alpha stereocenter on the enolate

Stereoselectivity: Alpha stereocenter on the electrophile

Stereoselectivity: Merged model for stereoinduction

Asymmetric aldol reaction

Evans' oxazolidone chemistry

References

See also

Contents

Mechanisms GA_googleFillSlot("encyclopedia_square");

Enol mechanism

Enolate mechanism

Control in the Aldol reaction

The problem

Acidity

Order of addition

Enolates

Formation

Geometry

Kinetic vs. thermodynamic enolates

Stereoselectivity

E vs. Z enolates

Metal ion

Stereoselectivity: Alpha stereocenter on the enolate

Stereoselectivity: Alpha stereocenter on the electrophile

Stereoselectivity: Merged model for stereoinduction

Asymmetric aldol reaction

Evans' oxazolidone chemistry

References

See also

Mechanisms