An Aldol Condensation Is an Organic Reaction in Which
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Aldol Condensation: An aldol condensation is an organic reaction in which an enol or an enolate ion reacts with a carbonyl compound to form a β- hydroxyaldehyde or β-hydroxyketone, followed by a dehydration to give a conjugated enone.
Aldol condensations are important in organic synthesis, providing a good way to form carbon–carbon bonds.
CHEMISTRY PAPER No. 9 : Organic Chemistry III (Reaction Mechanism-2) MODULE No.18: Aldol Condensation
E Enolate ions: When keto-enol tautomerism occurs the keto or enol is deprotonated and an anion, which is called the enolate, is formed as intermediate. Enolates can exist in quantitative amounts in strictly Brønsted acid free conditions, since they are generally very basic. In enolates the anionic charge is delocalized over the oxygen and the carbon . Enolates are somewhat stabilized by this delocalization of the charge over three atoms.
Enol form: Enols (also known as alkenols) are alkenes with a hydroxyl group affixed to one of the carbon atoms composing the double bond. Alkenes with a hydroxyl group on both sides of the double bond are called enediols. The C=C double bond with adjacent alcohol gives enols and enediols their chemical characteristics, by which they present keto-enol tautomerism. In keto-enol tautomerism, enols interconvert with ketones or aldehydes.
I IntramolecularAldol condensation: If in place of enolizable monocarbonyl compound, we start with an enolizable dicarbonyl compound, it leads to intramolecular Aldol reactions.This is because, the molecule shall have both the electrophilic as well as nucleophilic centre generated during the course of the reaction.This means the enolate component and the carbonyl component are parts of a single larger molecule.
CHEMISTRY PAPER No. 9 : Organic Chemistry III (Reaction Mechanism-2) MODULE No.18: Aldol Condensation
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Modern variations and methods of Aldol Reaction: Recent methodology now allows a much wider variety of aldol reactions to be conducted, often with a catalytic amount of chiral ligand. When reactions employ small amounts of enantiomerically pure ligands to induce the formation of enantiomerically pure products, the reactions are typically termed "catalytic, asymmetric". Acetate aldol reactions:
A key limitation to the chiral auxiliary approach described previously is the failure of N-acetyl imides to react selectively. An early approach was to use a temporary thioether group.
Mukaiyama aldol reaction:
The Mukaiyama aldol reaction is the nucleophilic addition of silyl enol ethers to aldehydes catalyzed by a Lewis acid such as boron trifluoride or titanium tetrachloride. The Mukaiyama aldol reaction does not follow the Zimmerman-Traxler mothod. It gives high levels of enantioselectivity and wide substrate scope.
The method works on unbranched aliphatic aldehydes, which are often poor electrophiles for catalytic, asymmetric processes. This may be due to poor electronic and steric differentiation between their enantiofaces.
CHEMISTRY PAPER No. 9 : Organic Chemistry III (Reaction Mechanism-2) MODULE No.18: Aldol Condensation
Crimmins thiazolidinethione aldol:
A more recent version of the Evans' auxiliary is the Crimmins thiazolidinethione. The yields, diastereoselectivities, and enantioselectivities of the reaction are, in general, high, although not as high as in comparable Evans cases. Unlike the Evans auxiliary, however, the thiazoldinethione can perform acetate aldol reactions and can produce the "Evans syn" or "non-Evans syn" adducts by simply varying the amount of (−)-sparteine. The reaction is believed to proceed via six- membered, titanium-bound transition states, analogous to the proposed transition states for the Evans auxiliary.
CHEMISTRY PAPER No. 9 : Organic Chemistry III (Reaction Mechanism-2) MODULE No.18: Aldol Condensation
Organocatalysis:
A more recent development is the use of chiral secondary amine catalysts. These secondary amines form transient enamines when exposed to ketones, which may react enantioselectively with suitable aldehyde electrophiles. The amine reacts with the carbonyl to form an enamine, the enamine acts as an enol-like nucleophile, and then the amine is released from the product all— the amine itself is a catalyst. This enamine catalysis method is a type of organocatalysis, since the catalyst is entirely based on a small organic molecule. In a seminal example, proline efficiently catalyzed the cyclization of a triketone:
CHEMISTRY PAPER No. 9 : Organic Chemistry III (Reaction Mechanism-2) MODULE No.18: Aldol Condensation
This reaction is known as the Hajos-Parrish reaction (also known as the Hajos-Parrish-Eder- Sauer-Wiechert reaction, referring to a contemporaneous report from Schering of the reaction under harsher conditions). Under the Hajos-Parrish conditions only a catalytic amount of proline is necessary (3 mol%). There is no danger of an achiral background reaction because the transient enamine intermediates are much more nucleophilic than their parent ketone enols. This strategy offers a simple way of generating enantioselectivity in reactions without using transition metals, which have the possible disadvantages of being toxic or expensive.
"Direct" aldol additions:
In the usual aldol addition, a carbonyl compound is deprotonated to form the enolate. The enolate is added to an aldehyde or ketone, which forms an alkoxide, which is then protonated on workup. A superior method, in principle, would avoid the requirement for a multistep sequence in favor of a "direct" reaction that could be done in a single process step. One idea is to generate the enolate using a metal catalyst that is released after the aldol addition mechanism. The general problem is that the addition generates an alkoxide, which is much more basic than the starting materials. This product binds tightly to the metal, preventing it from reacting with additional carbonyl reactants.
Time line:
Year Description Image
CHEMISTRY PAPER No. 9 : Organic Chemistry III (Reaction Mechanism-2) MODULE No.18: Aldol Condensation
1872 Aldol condensation was first discovered independently by Charles- Adolphe Wurtz and Alexander Borodin in 1872.
1957 More refined forms of the mechanism are known. In 1957, Zimmerman and Traxler proposed that some aldol reactions have "six-membered transition states having a chair conformation." This is now known as the Zimmerman–Traxler model. E- enolates give rise to anti products, whereas Z-enolates give rise to syn products.
CHEMISTRY PAPER No. 9 : Organic Chemistry III (Reaction Mechanism-2) MODULE No.18: Aldol Condensation
1970-1980 THe Evans' acyl oxazolidinone method developed in the late 1970s and 1980s by David A. Evans and coworkers, which control both relative stereochemistry (i.e., syn or anti) and absolute stereochemistry (i.e., R or S).
Weblinks :
1. www.chem.wisc.edu/areas/reich/chem547/1-carbonyl%7B12%7D.htm 2. www.chemtube3d.com/Enolates%20with%20aldehydes%20and%20keto
3. www.chemgapedia.de/.../aldolkondensation...aldol/gek_aldol.vscml.htm
4. www.mhhe.com/physsci/chemistry/carey5e/Ch18/ch18-3-5.html
5. www.mhhe.com/physsci/chemistry/carey5e/Ch18/ch18-3-5.html
Suggestive Reading:
Jerry March, Advanced Organic Chemistry, Fourth Edition.
CHEMISTRY PAPER No. 9 : Organic Chemistry III (Reaction Mechanism-2) MODULE No.18: Aldol Condensation
Wade, L. G. (2005). Organic Chemistry (6th ed.). Upper Saddle River, New Jersey: Prentice Hall. pp. 1056–66. ISBN 0-13-236731-9.
Smith, M. B.; March, J. (2001). Advanced Organic Chemistry (5th ed.). New York: Wiley Interscience. pp. 1218–23. ISBN 0-471-58589-0.
CHEMISTRY PAPER No. 9 : Organic Chemistry III (Reaction Mechanism-2) MODULE No.18: Aldol Condensation
P. S. Kalsi, Organic Reactions And Their Mechanisms
Named Organic Reactions By Thomas Laue, Andreas Plagens
CHEMISTRY PAPER No. 9 : Organic Chemistry III (Reaction Mechanism-2) MODULE No.18: Aldol Condensation