Enolate thermodynamic

Thermodynamic Enolate- Reversible deprotonation to give the most stable enolate more highly substituted C=C of the enol form... 

The enolization of 5a-3-ketones appears to be cleanly directed to C-2, whereas that of 5j5-3-ketones is less selective. Remote substituents can have a significant effect on the kinetic and thermodynamic enol acetylation of 5j3-steroids. ... 

Bromination of 5j5-3-ketones yields the equatorial 4 -bromo compounds (22) as the thermodynamic or kinetic products,although the presence of a considerable amount of 2-bromo isomer has been reported in bromination with phenyltrimethylammonium bromide-perbromide. This is in keeping with other evidence that enolization of 5j5-3-ketones is not specifically directed to C-4. Cleaner results would probably be obtained via thermodynamic enol acelylation. ... 

The method can be further improved using trimethylsilyl (TMS) enol ethers, which can be prepared in situ from aldehydes and ketones [49]. TMS enol ethers of cyclic ketones are also suitable, and diversity can be enhanced by making either the kinetic or thermodynamic enol ether, as shown for benzyl methyl ketone. Thus, reaction of the kinetic TMS enol ether 10-133 with the amino aldehyde 10-134 and dimethylbarbituric acid 10-135 yielded 10-136, whereas the thermodynamic TMS enol ether 10-137 led to 10-138, again in excellent purity, simply by adding diethyl ether to the reaction mixture (Scheme 10.33). 

It is important to perform both the Birch reduction of 5 and the alkylation of enolate 6 at —78 °C. Enolate 6 obtained directly from 5 at low temperatures is considered to be a kinetic enolate . A thermodynamic enolate obtained from 6 by equilibration techniques has been shown to give an opposite sense of stereoselection on alkylation. Although a comprehensive study of this modification has not been carried out, diastereoselectivities for formation of 8 were found to be greater than 99 1 for alkylations with Mel, EtI, and PhCH2Br. Thus, it should be possible to obtain both enantiomers of a target structure by utilization of a single chiral benzamide. SE... 

The use of DAMgBr 39 in Et20/HMPA/TMSCPEt3N leads to the thermodynamic enolates or silyl enol ethers. This methodology is one of the best direct regiospecific preparations of thermodynamic silylenol ethers from unsymmetric cyclic ketones. 

With a weaker base and / or slow addition of base to the ketone, an equilibrium will be established and a "thermodynamic enolate" will predominate. 

Notes Shown to be an extremely useful base for generating thermodynamic enolates. Useful for alilol condensations. 

A total synthesis of ( )-aromatin has utilized the lithium anion of the dithiane of (E)-2-methyl-2-butenal as a functional equivalent of the thermodynamic enolate of methyl ethyl ketone in an aprotic Michael addition (Scheme 189) (81JOC825). Reaction of the lithium anion (805) with 2-methyl-2-cyclopentenone followed by alkylation of the ketone enolate as its copper salt with allyl bromide delivered (807). Ozonolysis afforded a tricarbonyl which cyclized with alkali to the aldol product (808). Additional steps utilizing conventional chemistry converted (808) into ( )-aromatin (809). 

Reaction of unsymmetrical ketones with strong bases may lead to two different enolates. Whether the eventual product derives from the more stable ( thermodynamic ) enolate, or from the more rapidly formed ( kinetic ) enolate, depends on reaction conditions. 

Identify the thermodynamic enolate for each system shown above (2-pentanone enolate A and B 2-methylcyclopentanone enolate A and B decalinone enolate A and B). Also, compare electrostatic potential maps for each pair of enolates. What structural and/or electronic features, if any, appear to dictate which enolate is favored ... 

In contrast, a-nitroalkenation adducts (298) are obtained with thermodynamic enolates of a-sub-stituted ketones or esters in addition, Fuji reports that enantioselective addition of a-subsdtuted lactone enolates to chiral nitroenamines is cation dependent with zinc affording maximum enantioselectivity.213... 

The enolate that is die most stable usually has die most highly substituted double bond and is called the thermodynamic enolate. If a slight excess of the ketone is used or a trace of protic impurities is present, equilibrium between die enolates is established and isomerization to die more highly substituted enolate occurs. 

The thermodynamic enolate is lower in energy so it is the one favored if equilibrium is achieved. For this reason, great care must be taken in die preparation and... 

The enolate anions are more reactive towards electrophiles when they are associated with non-coordinating quaternary ammonium cations than when they are associated with lithium cations. Thus, as illustrated in Equations Si3.4 and Si3.5, quaternary ammonium derivatives are preferred as counterions for kinetic enolates in order to prevent any isomerization to the thermodynamic enolate occurring before reaction with the added electrophile proceeds. 

The treatment of the thermodynamic enolate of 2-methylcyclohexanone with ethynyl(phenyl)iodonium tetrafluoroborate in tetrahydrofuran affords 2-ethynyl-2-methylcyclohexanone (equation 267). This is the only example known to this author of the alkynylation of an unactivated monocarbonyl compound with an alkynyliodonium salt. However, the earlier conclusion that simple enolates do not undergo alkynylation with alkynyliodonium salts (section II.D.7 and II.G) needs to be revvised. 

We thus reach the following interesting result. Depending on the reaction conditions, both the kinetic and the thermodynamic enolates of 2-phenylcyclohexanone can be generated with perfect regiocontrol. The same is true for many ketones that carry a different number of alkyl groups at the Ca and Ca< centers. 

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