Stabilisation of enolates

Metals and Ligand Reactivity, New Edition. Edwin C. Constable Copyright 1996 VCH Verlagsgesellschaft mbH, Weinheim ISBN 3-527-29278-0 

3-diketonate anions which are formed are excellent didentate chelating ligands for transition metals. In general, the formation of a diketonate complex is so favourable that simply treating a metal salt with the 1,3-diketone in the presence of a mild base results in the formation of a complex of the deprotonated ligand. In some cases, it is not necessary to add an external base - another ligand co-ordinated to the metal centre may be capable of acting as the base (Fig. 5-3). 

Aza-analogues of oxygen compounds frequently show related reactivity patterns, and this is certainly seen in a comparison of the chemistry of imines and carbonyl compounds. For example, 1,3-diimines are readily deprotonated to yield the 1,3-diketonate analogues. The most frequent consequence of this is that reactions which are expected to yield 1,3-diimine complexes often lead to those of the deprotonated species. This is seen in the formation of the gold(m) complex of a deprotonated macrocycle in the reaction of 1,2-diaminoethane with 2,4-pentanedione in the presence of Na[AuCl4] (Fig. 5-4). The exact sequence of events in this reaction is not known, but note that the product is a square-planar gold(in) complex of the doubly-deprotonated macrocycle, rather than a gold(i) species  

In relatively few cases, separate complexes containing both the protonated and the deprotonated forms of the ligands may be isolated, and it is then possible to directly determine the pKa values for the co-ordinated ligands (Fig. 5-5). 

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Another feature that will serve to stabilise the enol, with respect to the keto, form is the possibility of strong, intramolecular hydrogen bonding, e.g. in MeCOCH2COMe (31) and MeC0CH2C02Et (23) ... 

The stabilisation of an enolate (intermediate or product) is also important in the decarboxylation reaction of /3-ketoacids. The decarboxylation of such compounds is facile, and is the key to the synthetic utility of ethyl acetoacetate and diethyl malonate. The mechanism of decarboxylation involves the formation of an enol (Fig. 5-21), and so is expected to be subject to metal ion control. 

However, if a further donor group is introduced, a chelate may be formed that does not involve the carboxylate group to be lost. In these cases, the decarboxylation is dramatically enhanced in the presence of metal ions. This is exactly the situation which pertains with oxalacetic acid, which undergoes a facile metal-promoted decarboxylation (Fig. 5-23). The rate of decarboxylation of oxalacetic acid is accelerated some ten thousand times in the presence of copper(n) salts. The metal ion is thought to play a variety of roles, including the stabilisation of the enolate that is produced after loss of carbon dioxide. 

The role of the metal ion may be purely conformational, acting to place the reactants in the correct spatial arrangement for cyclisation to occur, or it may play a more active role in stabilising the enol, enolate, imine or enamine intermediates. The prototypical example of such a reaction is shown in Fig. 6-18. The nickel(n) complex of a tetradentate macrocyclic ligand is the unexpected product of the reaction of [Ni(en)3]2+ with acetone. There are numerous possible mechanisms for the formation of the tetradentate macro-cyclic ligand and the exact mechanism is not known with any certainty. 

In chapter 21 we mentioned nitro compounds as promoters of conjugate addition they also stabilise anions strongly but do not usually act as electrophiles so that self-condensation is not found with nitro compounds. The nitro group is more than twice as good as a carbonyl group at stabilising an enolate anion. Nitromethane (p/ a 10) 1 has a lower pKa than malonates 4 (pKa 13). In fact it dissolves in aqueous NaOH as the enolate anion 3 formed in a way 2 that looks like enolate anion formation. 

The enhanced acidity of carboxylic acids and enols relative to alcohols has long been attributed to the stabilisation of the carboxylate and enolate anions by delocalisation of their n electrons (see 1 and 2 below). Alkoxide anions, as saturated systems, are not subject to resonance stabilisation. 

In acidic conditions, deuteriation at the methylene group of benzyl methyl ketone is also preferred with a ratio kJk xOA (Roques, 1972) which corresponds to a difference of about 1.3 kcal mol-1 between the two transition states. This result can be ascribed to the conjugative stabilisation of the /l2,3-enol [481 compared with the zll,2-enol [49]. Since the difference... 

The changing perspective on the viability of fluorine as a reagent is illustrated by the fact that many selective fluorinations of substrates [8] containing carbon centres of high electron density have now been described, including a variety of enolate derivatives [71, 72], stabilised carbanions [73, 74], steroids [75] and 1,3-dicarbonyl derivatives [76] (Table 3.2) as well as some aromatic compounds [77]. Fluorinated aminoacids have been obtained by direct fluorination [78] (Figure 3.10). 

Probably the aromatisation is due to the stabilisation of the tautomeric enolic form of 131 in the experimental conditions... 

Very little data on the Hildebrand solubility parameters of ionic liquid-solute systems is available to date. A study of eight ionic liquids using viscosity measurements in different solvents indicated polarities similar to allyl alcohol or dimethylsulfoxide [35], More recent work has shown that the solubility parameters can be reliably estimated from surface tension and density measurements [36], The equilibrium position of keto-enol tautomers in conjunction with quantitative H-NMR-, IR- and UV/Vis-spectroscopy has been studied in ionic liquids [37, 38], where the stabilisation of the enol form is favoured in non-polar solvents in general. Comparison to the relative tautomer ratios obtained in methanol and acetonitrile indicated that even hydrophobic (non-polar) [BTA]-based ionic liquids were more polar than these organic solvents. 

The glycosaminoglycan epimerases are part of a superfamily of lyases and epimerisases whose active sites stabilise carboxyl enolates, similar to the mannuronate epimerases in alginate biosynthesis. ... 

The observation that L-arabinal adopted the conformation exclusively and that the and conformations of o-glucal were comparably populated led Curran and Suh" to propose a vinylogous anomeric effect , similar to the anomeric effect. Additional stabilisation of an electronegative substituent in an axial orientation was available from a p-type lone pair on oxygen, separated by a double bond, via overlap of the C X a orbital and v /2 of the enol ether (Figure 6.70). No experimental estimates of its magnitude are available, but it is likely to be smaller than the anomeric effect itself, not least because any electrostatic component is much smaller. 

The Family 3 structure is similar in structure to Family 1 pectate lyases, the pectate lyase of a Bacillus species being a parallel eight-turn (3-helix.Site-directed mutagenesis experiments supported a role for an arginine as the active site base that deprotonated C5, with a role for the second Ca " in stabilising the enolate (the first Ca " being structural). It is possible that the very existence of a Family 3 PL, separate from Family 1, is an artefact of the many basic residues incorporated into this enzyme that ensure its alkaline pFl optimum. 

Quantitative measures for some methyl deprotonations are 2-methylpyridine (pK 34), 3-methylpyridine (pK 37.7), 4-methylpyridine (pK 32.2), 4-methylquinoline (pK 27.5). ° These values can be usefully compared with those typical for ketone a-deprotonation (19-20) and toluene side-chain deprotonation (-41). Thus, strong bases can be used to convert methyl-pyridines quantitatively into side-chain anions, however the enolate-like stabilisation of the anion is sufficient that reactions can often be carried out using weaker bases under equilibrating conditions, i.e. under conditions where there is only a small percentage of anion present at any one time. It may be that under such conditions, side-chain deprotonation involves iV-hydrogen-bonded or iV-coordinated pyridines. 

The activating group stabilises the enolate anion (9) by conjugation so that the keto ester (8) can be converted entirely into (9) with EtO. No reaction of... 

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