Enolates experimental studies

The syn TS is favored by about 1 kcal/mol, owing to reduced eclipsing, as illustrated in Figure 1.4. An experimental study using the kinetic enolate of 3-(/-butyl)-2-methylcyclopentanone in an alkylation reaction with benzyl iodide gave an 85 15 preference for the predicted cis-2,5-dimethyl derivative. 

The polar solvent effect on relative acidities of carboxylic acids and enols was studied by Wiberg et al.179 by means of the DFT(B3LYP)/SCRF and MP2/SCRF calculations. Both methods well reproduced experimental solvent effects. 

There are only few experimental studies where the importance of the oxyanion hole for stabilizing the enolate oxyanion has been quantified. Tonge and collaborators [21] have studied the properties of the Glyl41Pro variant of hydratase. In this variant, one of the two peptide NH groups of the oxyanion hole (N(Glyl41)) has been disabled because of the Glyl41Pro mutahon. Compared to the wild-type enzyme, kcat is reduced 10 -fold, whereas is not affected. In addition, Raman studies suggest that the active site of the variant remains intact. 

Let us consider a problem that arose in connection with an experimental study. Propanone (acetone) was subjected to ionization followed by neutralization of the radical cation, and the products were frozen in an inert matrix and studied by IR spectroscopy [13]. The spectrum of the mixture suggested the presence of the enol isomer of propanone, 1 -propen-2-ol (Reaction 2.2) ... 

In other words, the C- -Nu bond lies closer to CH than to CR when projected on to the carbonyl plane. This can be translated as a rotation of the aldehyde shown by the arrows in structures 35-38. This rotation diminishes the R-R2 repulsion in 35 and increases the R-Ra repulsion in 36. If these repulsions were of similar magnitude before the rotation, the erythro transition state 35 will be favored over the threo precursor 36. The R-R2 distance in 35 being smaller than R-Ra in 36, this condition is only met when R2 Rj. Hence the prediction that (Z)-enolates will give erythro aldols when R2 is significantly less bulky than Rr The percentage of threo product should rise as the size of R2 increases. This hypothesis agrees nicely with experimental studies conducted by Fellman and Dubois140 ... 

The mechanism of oxygen transfer from oxaziridines to nucleophiles is believed to involve an Sn2 type reaction and this assumption is supported by theoretical and experimental studies. When sulfides are oxidized to the corresponding sulfoxides and sulfones, the molecular recognition is steric in origin, and it is determined by the substituents on both the substrate and the oxaziridine. For the oxidation of enolates, the molecular recognition is explained with an Sn2 mechanism as well as by an open (non-chelated) transition state where the nonbonded interactions are minimized. The mechanism of oxygen transfer to an enolate to form the corresponding acyloin is shown below. ... 

Several experimental studies of the asymmetric Rh-catalysed cyclopropanation of alkenes with diazocompounds as rhodium carbenoid precursors have been reported. The perfluoroalkylated dirhodium complex (44) has proved efficient for catalysing the reaction between aryldiazocompounds and electron-rich styrenes on enol ethers with a good cw-diastereoselectivity but poor enantioselectivity. The dirhodium complexes (45) and (46), have both permitted the successful cyclopropanation of 0 -diazopropionates (47) and of diverse doubly stabilized diazocompounds (48). Both (45)/(47) and (46)/(48) combinations thus enabled formation of valuable cyclopropanes possessing at least one quaternary carbon in good yields and high diastereo- and enantio-selectivities. Noteworthy is that in the case of (48), the paramethoxyaryl-ketone moiety has been found to play a key role in the stereoinduction process. 

There has been a summary of computational and experimental studies of the use of palladium complexes with A -heterocyclic carbenes (NHCs) in the asymmetric coupling of -hybridized carbon-hydrogen bonds with aryl halides. It has been shown that the electronic and catalytic properties of NHCs fused to porphyrins may be modified by varying the inner metal in the porphyrin. A DPT study of the use of palladium-NHC complexes in the asymmetric intramolecular a-arylation of 2-bromoaryl amides to give 3,3-disubstituted oxindoles (101) has been reported. The likely pathway involves insertion of the palladium into the arene-bromine bond to form a palladacycle which deprotonates to give an (9-enolate. Conversion into the C-enolate followed by reductive elimination gives the product. The intramolecular reaction of 0 a cyclopropane carbon-hydrogen bond in a 2-bromoanilide derivative has been used to form cyclopropyloxindoles, (102), in a palladium-catalysed, silver-mediated reaction. 

Experimental studies demonstrated that curcumin prevents and may even be a cure for Alzheimer s disease and can be a prevention agent and a chemotherapeutic agent for colon cancer. In addition, curcumin shows potent anti-inflammatory and antioxidant activity (the most favoured antioxidant is the enol form). Recombination... 

The tautomerism of halo-derivatives, like 5-bromouracil, appears to be more interesting, since it has been related to the mutagenicity of these compounds [109]. Early experimental studies [138] suggested that a certain percentage of enol tautomer of 5-bromouracil might exist in aqueous solution, which could explain the ability of 5-bromouracil to induce G->A mutations (see Figure 9). Very recent high level ab initio calculations combined with MC-FEP and ab initio SCRF calculations do not support this hypothesis, since the presence of the bromine atom at position 5 is not found to introduce major... 

For malondialdehyde (selected structures 27,28 in Figure 6.8) only experimental studies have been found regarding in-solution equilibria. The structure of the enol-keto form, H0-CH=CH-CH=0 (28), comprises a conjugated doublebond system subject to s-cisis-tmns conformational isomerism about the CH-CH bond [14]. A cis-trans isomerism comes into existence regarding the CH=CH double bond. Considering also the rotational flexibihty of the alcohol hydrogen in the OH group, a number of structurally different species could be present in the equUibrium composition. 

As in the case of benzothiazoles and benzimidazoles, the excited-state proton transfer in 2-(2 -hydroxyphenyl)benzoxazole was studied both experimentally and computationally. The results closely resemble the observations for the other species The cw-enol form is preferred in the Sq ground state and the cw-keto form in the 5i excited state. Moreover, the proton transfer appears to be due to vibrational relaxation rather than thermal activation, suggesting that the aromatic ring has an impact on the transfer reaction of these systems [95JPC12456, 99JST255]. 

First of all, the mesomerism of HBI is rendered complex by the presence of several protonable groups actually, HBI might exist, depending on pH, under cationic, neutral, zwitterionic, anionic, and possibly enolic forms (Fig. 3a). The experimental p/sTa s of model analogs of HBI in aqueous solutions have been studied. Titration curves follow two macroscopic transitions at pH 1.8 and pH 8.2, each corresponding to a single proton release [69]. Comparison of theoretical... 

Depke, G., N. Heinrich, and H. Schwarz. 1984. On the Gas Phase Chemistry of Ionize Glycine and Its Enol. A Combined Experimental and Ab Initio Molecular Orbital Study. Int. J. Mass Spectrom. Ion Porcesses 62, 99-117. 

The isolation of calycanthine (9) in 1888 by Eccles [28] and the subsequent proposition for its origins in the oxidative dimerization of tryptamine by Woodward [29] and Robinson [30] had prompted several key synthetic studies based on a biomimetic approach. Hendrickson was the first to experimentally verify the plausibility of forming the C3-C3 linked dimers through an oxidative radical dimerization strategy (Scheme 9.2a). He demonstrated that the sodium enolate of a tryptamine-derived oxindole could be oxidized with iodine to afford a mixture of three possible stereoisomers. The racemic product was isolated in 13 % yield, while the meso product was isolated in 8 % yield. Global reduction of the oxindole and carbamates afforded the first synthetic samples of chimonanthine (7) [9a],... 

Enol esters are distinct from other esters not because of a particular stability or lability toward hydrolases, but due to their hydrolysis releasing a ghost alcohol (an enol), which may immediately tautomerize to the corresponding aldehyde or ketone. A well-studied example is that of vinyl acetate (CH3-C0-0-CH=CH2), a xenobiotic of great industrial importance that, upon hydrolysis, liberates acetic acid (CH3-CO-OH) and acetaldehyde (CH3-CHO), the stable tautomer of vinyl alcohol [25], The results of two studies are compiled in Table 7.1, and demonstrate that vinyl acetate is a very good substrate of carboxylesterase (EC 3.1.1.1) but not of acetylcholinesterase (EC 3.1.1.7) or cholinesterase (EC 3.1.1.8). The presence of carboxylesterase in rat plasma but not in human plasma explains the difference between these two preparations, although the different experimental conditions in the two studies make further interpretation difficult. 

In the titanium tetrachloride-promoted aldol condensations of stereochemically defined enolsilanes (eq. [58]) variable levels of aldol diastereoselection have been noted (Table 26) (73). A detailed analysis of this reaction in terms of probable intermediates and transition state awaits further studies however, some experimental observations suggest that titanium enolates may not be involved (73b). 

The Berkeley group studied the following different experimental conditions A) addition of Lewis acid, at -78 °C, in one portion to the boron enolate in CH2CI2 solution, followed by addition of the aldehyde in a 30-min period B) addition of Lewis acid via syringe in a 3-4 h period after the aldehyde has been added in one portion C) the aldehyde was precomplexed with Lewis acid in CH2CI2 at -78 °C and the boron enolate was added to the cold solution. The results are summarised in Table 9.7. 

In 1998, Hasanayn and Streitwieser reported the kinetics and isotope effects of the Aldol-Tishchenko reaction . They studied the reaction between lithium enolates of isobu-tyrophenone and two molecule of beuzaldehyde, which results iu the formation of a 1,3-diol monoester after protonation (Figure 28). They analyzed several aspects of this mechanism experimentally. Ab initio molecular orbital calculatious ou models are used to study the equilibrium and transition state structures. The spectroscopic properties of the lithium enolate of p-(phenylsulfonyl) isobutyrophenone (LiSIBP) have allowed kinetic study of the reaction. The computed equilibrium and transition state structures for the compounds in the sequence of reactions in Figure 28 are given along with the computed reaction barriers and energy in Figure 29 and Table 6. 

Apparently, these results implied an inverse relationship between reactivity and selectivity, with the reactivity of the carbocation measured by the inverse of the rate constant for solvolysis. This indeed was not unexpected in the context of a general perception that highly reactive reagents, especially reactive intermediates such as carbocations, carbanions, or carbenes are unselective in their reactions.257 259 Such a relationship is consistent with a natural inference from the Hammond postulate258 and Bell-Evans-Polanyi relationship,260 and is illustrated experimentally by the dependence of the Bronsted exponent for base catalysis of the enolization of ketones upon the reactivity of the ketone,261,262 and other examples21,263 including Richard s careful study of the hydration of a-methoxystyrenes.229... 

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