Keto-enols formation

K-13 1315, 1321 synthesis of 1318 Kalman filter 929, 987 Katsurenone, synthesis of 1240, 1245 Kerosene, phenohc compounds in 948 Ketenes—see Dienylketenes Ketides—see Polyketides Keto-enols, formation of 1028 Ketones,... 

Mechanism of base-catalyzed enol formation. The intermediate enolate ion, a resonance hybrid of two forms, can be protonated either on carbon to regenerate the starting keto tautomer or on oxygen to give an enol. 

Importance of enol formation for y keto ester fluorination... 

GL 4] [R 5] [P 5] The rate of the fluorination of y0-keto esters is usually correlated with the enol concentration or the rate of enol formation as this species is actually fluorinated [15, 16]. For the fluorination of ethyl 2-chloroacetoacetate in a micro reactor, much higher yields were found as expected from such relationships and as compared with conventional batch processing which has only low conversion. Obviously, the fluorinated metal surface of the micro channel promotes the enol formation. 

The preparation of ketones and ester from (3-dicarbonyl enolates has largely been supplanted by procedures based on selective enolate formation. These procedures permit direct alkylation of ketone and ester enolates and avoid the hydrolysis and decarboxylation of keto ester intermediates. The development of conditions for stoichiometric formation of both kinetically and thermodynamically controlled enolates has permitted the extensive use of enolate alkylation reactions in multistep synthesis of complex molecules. One aspect of the alkylation reaction that is crucial in many cases is the stereoselectivity. The alkylation has a stereoelectronic preference for approach of the electrophile perpendicular to the plane of the enolate, because the tt electrons are involved in bond formation. A major factor in determining the stereoselectivity of ketone enolate alkylations is the difference in steric hindrance on the two faces of the enolate. The electrophile approaches from the less hindered of the two faces and the degree of stereoselectivity depends on the steric differentiation. Numerous examples of such effects have been observed.51 In ketone and ester enolates that are exocyclic to a conformationally biased cyclohexane ring there is a small preference for... 

Some representative Claisen rearrangements are shown in Scheme 6.14. Entry 1 illustrates the application of the Claisen rearrangement in the introduction of a substituent at the junction of two six-membered rings. Introduction of a substituent at this type of position is frequently necessary in the synthesis of steroids and terpenes. In Entry 2, formation and rearrangement of a 2-propenyl ether leads to formation of a methyl ketone. Entry 3 illustrates the use of 3-methoxyisoprene to form the allylic ether. The rearrangement of this type of ether leads to introduction of isoprene structural units into the reaction product. Entry 4 involves an allylic ether prepared by O-alkylation of a (3-keto enolate. Entry 5 was used in the course of synthesis of a diterpene lactone. Entry 6 is a case in which PdCl2 catalyzes both the formation and rearrangement of the reactant. 

The formation of methyl-oxazole compounds was also described by Wang et al. [34] utilizing an analog of the keto-enol intermediate (22) described in Sect. 2.1.1, Scheme 2. Scheme 11 shows the synthesis of compound 57 which exhibits anti-tubulin activity of 7.7. iM [34], In addition, a range of oxazole COX-2 inhibitors has been reported by Hashimoto et al. [55] employing similar chemistry. 

Although Eibner elucidated the structure between 1904 and 1906, it was only through IR and nuclear magnetic resonance spectroscopy (NMR) that the chro-maticity of these molecules could be attributed to keto-enol tautomerism and simultaneous hydrogen bond formation (structures 137a = 137b) [2]. 

If one considers a TMS group to be equivalent to a proton, a recent paper describes the formation of a phosphanyl-substituted allene by a keto-enol tautomer-ization-like silyl migration [346],... 

Second reaction. Air is not required for formation of the keto-enol. The C1-C6 and 07-08 bonds are broken, and a new Cl-0 bond is made. It makes sense that the driving force for breaking the C1-C6 bond should be provided by migrating Cl from C6 to 07 (note a 1,2-shift) and expelling 08. Then 08 can add back to C6 to give a hemiketal which can open up to the ketone. 

There is a distinct relationship between keto-enol tautomerism and the iminium-enamine interconversion it can be seen from the above scheme that enamines are actually nitrogen analogues of enols. Their chemical properties reflect this relationship. It also leads us to another reason why enamine formation is a property of secondary amines, whereas primary amines give imines with aldehydes and ketones (see Section 7.7.1). Enamines from primary amines would undergo rapid conversion into the more stable imine tautomers (compare enol and keto tautomers) this isomerization cannot occur with enamines from secondary amines, and such enamines are, therefore, stable. 

By means of in situ NMR spectroscopy combined with deuterium incorporation experiments, van Leeuwen has elucidated the mechanism of termination by protonolysis, showing that the fl-chelates are in equilibrium with their enolate form by a p-H elimination/hydride migration process (Scheme 7.19). The enolate intermediates are regioselectively protonated at the C2 carbon atom by either MeOH or H2O to give Pd-OMe or Pd-OH and keto terminated copolymer. The enolate formation has been reported to be rate determining in the chain transfer [19]. 

These seemingly anomalous results suggest that the formation and fragmentation of a-amino nitrite esters could be playing a central role in the nitrosation of aminopyrine. The characterization of both fast and slow reactions, as well as the identification of two pH optima, imply that more than one kinetically significant pathway is involved in the overall transformation. The mechanism of Fig. 5a could well be the first order component the kinetic studies show to be operative under some conditions. It is noteworthy that this pathway also leads directly in its final step to the keto-enol derivative IV, which Mirvish et al. have identified as a by-product of aminopyrine nitrosation. 

Even for a simple reaction, involving just one reactant species and one product species, such as a keto-enol tautomerism or a cis-trans isomerization, the above equation for a given solvent is complicated. StUl, in specific cases it is possible to unravel the solvent effects of cavity formation, for the solute species have different volumes, polarity/polarizability if the solute species differ in their dipole moments or polarizabilities, and solvent Lewis acidity and basicity if the solutes differ in their electron-pair and hydrogen-bond acceptance abilities. 

We note that for the case of keto/enol interconversion, it is simple, useful and remarkably accurate to equate the difference of Gibbs energies in aqueous media of the two tautomers and the difference of enthalpies of formation in the gas J. R. Keefe and A. J. Kresge, J. Phys. Org. Chem., 5, 575 (1992). We are pleased. 

The enol form and the carbanion-enolate being inactive, the height of the keto form is determined by the rate of reaction (25 c) in competition with reaction (25 d). The rate of the ketone formation increases with increasing pH because the rate of the faster enol-formation k T decreases. Consequently, the height of the more negative wave at the potential E3 (for which only the over-all reaction is given in (25 e)) increases with increasing pH (Fig. 19). 

The addition of water to an alkyne leads to the formation of an unstable vinyl alcohol. These unstable materials undergo keto-enol tautomerization to form ketones. The hydration of propyne forms 2-propanone, as the following figure illustrates. 

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