Enol-type

The more common types of structure showing tautomerism are the keto-enol type. 

A mixture of an acid anhydride and a ketone is saturated with boron trifluoride this is followed by treatment with aqueous sodium acetate. The quantity of boron trifluoride absorbed usually amounts to 100 mol per cent, (based on total mola of ketone and anhydride). Catalytic amounts of the reagent do not give satisfactory results. This is in line with the observation that the p diketone is produced in the reaction mixture as the boron difluoride complex, some of which have been isolated. A reasonable mechanism of the reaction postulates the conversion of the anhydride into a carbonium ion, such as (I) the ketone into an enol type of complex, such as (II) followed by condensation of (I) and (II) to yield the boron difluoride complex of the p diketone (III) ... 

The formation of the above anions ("enolate type) depend on equilibria between the carbon compounds, the base, and the solvent. To ensure a substantial concentration of the anionic synthons in solution the pA" of both the conjugated acid of the base and of the solvent must be higher than the pAT -value of the carbon compound. Alkali hydroxides in water (p/T, 16), alkoxides in the corresponding alcohols (pAT, 20), sodium amide in liquid ammonia (pATj 35), dimsyl sodium in dimethyl sulfoxide (pAT, = 35), sodium hydride, lithium amides, or lithium alkyls in ether or hydrocarbon solvents (pAT, > 40) are common combinations used in synthesis. Sometimes the bases (e.g. methoxides, amides, lithium alkyls) react as nucleophiles, in other words they do not abstract a proton, but their anion undergoes addition and substitution reactions with the carbon compound. If such is the case, sterically hindered bases are employed. A few examples are given below (H.O. House, 1972 I. Kuwajima, 1976). 

Reagents with carbonyl type groupings exhibit a or (if n. S-unsaturated) a properties. In the presence of acidic or basic catalysts they may react as enol type electron donors (d or d reagents). This reactivity pattern is considered as normal . It allows, for example, syntheses of 1,3- and 1,5-difunctionaI systems via aldol type (a -H d or Michael type (a + d additions. 

A classical reaction leading to 1,4-difunctional compounds is the nucleophilic substitution of the bromine of cf-bromo carbonyl compounds (a -synthons) with enolate type anions (d -synthons). Regio- and stereoselectivities, which can be achieved by an appropiate choice of the enol component, are similar to those described in the previous section. Just one example of a highly functionalized product (W.L. Meyer, 1963) is given. 

Due to mechanistic requirements, most of these enzymes are quite specific for the nucleophilic component, which most often is dihydroxyacetone phosphate (DHAP, 3-hydroxy-2-ox-opropyl phosphate) or pyruvate (2-oxopropanoate), while they allow a reasonable variation of the electrophile, which usually is an aldehyde. Activation of the donor substrate by stereospecific deprotonation is either achieved via imine/enamine formation (type 1 aldolases) or via transition metal ion induced enolization (type 2 aldolases mostly Zn2 )2. The approach of the aldol acceptor occurs stereospecifically following an overall retention mechanism, while facial differentiation of the aldehyde is responsible for the relative stereoselectivity. 

A number of lyases are known which, unlike the aldolases, require thiamine pyrophosphate as a cofactor in the transfer of acyl anion equivalents, but mechanistically act via enolate-type additions. The commercially available transketolase (EC 2.2.1.1) stems from the pentose phosphate pathway where it catalyzes the transfer of a hydroxyacetyl fragment from a ketose phosphate to an aldehyde phosphate. For synthetic purposes, the donor component can be replaced by hydroxypyruvate, which forms the reactive intermediate by an irreversible, spontaneous decarboxylation. 

However, this is not so easy without the tertiary structure of the enzyme. The possible clues are the homology search with functionally resembling enzymes and computer simulation of the tert-structure of the enzyme. The characteristic features of AMDase are (i) the reaction proceeds via an enolate-type transition state, (ii) the cysteine residue plays an essential role and (iii) the reaction involves an inversion of configuration on the a-carbon of the carboxyl group. 

This planar conformation will also favor forming an enolate-type intermediate or transition state, as estimated from the Hammett plot, since the p-orbitals of the phenyl ring are already arranged in the best positions to be able to conjugate with the developing p-orbital of the enolate. 

Mltsulshi et al. described (20) that 4-OH was in the hydrazo form in polar solvents, and azo form in nonpolar solvents. It was suggested that one hydrogen atom of the hydroxide group at the 4-positlon of the naphthalene ring transferred to the 3-positlon of the azo group, and the tautomerism was established between hydrazo form of the keto type and the azo form of the enol type. In this study, we consider that the spectrum with a peak at the 480 nm... 

Other important examples of stable enol-type compounds are the aromatic alcohols, or phenols. The K s of these compounds are about 10 10, some 10s times larger than the Ka s for alcohols. 

Unlike phenols (Section 26-l), structural analysis of many of the hydroxy-substituted aza-aromatic compounds is complicated by isomerism of the keto-enol type, sometimes called lactim-lactam isomerism. For 2-hydro xypyrimidine, 19, these isomers are 19a and 19b, and the lactam form is more stable, as also is true for cytosine, 15, thymine, 16, and the pyrimidine ring of guanine, 18. 

Alkylation of chiral 2-(aminomediyl)oxazoline (105 Z = CH2Ph) at the exocychc carbon—using -butyllithium and an alkyl hahde—proceeds with negligible de. However, when the amine reactant is changed to a carbamate, e.g. (105 Z = C02Ph), the products exhibit up to 92% de.m This is ascribed to a preferred formation of an U-enolate-type intermediate during deprotonation, due to complexation of the lithium by the carbamate carbonyl. 

Bis-carboxonium ions such as 73 can be directly observed using low-temperature NMR. In the case of 73, 2,4 pentanedione is dissolved in FS0sH-SbF5-S02 solution at — 60°C and the 1H NMR shows three absorptions, including the carboxonium protons.32 In some cases (especially in weaker superacid systems), the diprotonated species form equilibrium mixtures with the monoprotonated species. When either 1,3-cyclohexane-dione or 2-methyl-l,3-cyclopentanedione is reacted in very strong superacids, only the monoprotonated species are observed.32 This is attributed to increased stability of the enol-type cations, 90 and 91, when compared with the acyclic systems. 

Triarylantimony(V) bromides react with fluorinated /9-diketones in the presence of triethylamine to yield the oxygen bridged enol type /3-diketone complex (Ar3SbL)20, which when heated in moist organic solvent yields hydrated /8-diketone complexes of... 

Phosphonate esters can be deprotonated with sodium hydride or alkoxide anions to give enolate-type anions that react well with aldehydes or ketones to give -alkenes. Alkene-forming reactions with phosphonates are called Horner-Wadsworth-Emmons (or Horner-Emmons, Wadsworth-Emmons, or even Horner-Wittig) reactions. This example is a reaction that was used by some Japanese chemists in the synthesis of polyzonimine, a natural insect repellent produced by millipedes. 

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