Enamines kinetic deprotonation

Results of a kinetic study of enamine formation by C(2a)-proton abstraction from 2-benzylthiazolium salts (88) have implications for mechanistic studies of the thiamin diphosphate-dependent enzymes which feature protonation of the enamine/C(2a)-carbanion.151 The primary isotope effect for deprotonation of (88a) is kiw/kro = 4-6 and the values estimated for C(2a)—H pXa are 15.0-15.5 and 15.7 for (88a) and (88b), respectively. A minimum effective molarity of 4500 M has been estimated for reprotonation of the enamine (89b) derived from (88b) by benzoylformate decarboxylase. Directed aromatic metallation reactions have been reviewed.152... 

Many reactions have also been carried out in water. The mechanisms of the reactions of acetone and 1,3-dihydroxyacetone using zinc-proline and related catalysts have been probed kinetically.98 The former exhibits an enamine route, whereas the latter involves rate-limiting deprotonation of the -carbon and formation of an enolate. An umbelliferyl ether of dihydroxyacetone (37) has been used as a fluorogenic probe for enolization, which may prove useful in screening of aldolases in water. 

The kinetics of deprotonation leading to the enamine had been investigated by several groups using isotope exchange kinetics24-27, as well as triiodide trapping of the... 

Rivire and Lattes used LiNH2 and NaNHj in liquid ammonia at — 70°C, in hexamethylphosphortriamide at room temperature or t-BuOK/HMPA at room temperature for allylamine enamine isomerizations. An anion formed by deprotonation of the allylamine at C was considered to be the intermediate species in the isomerization. Intramolecular transfer of hydrogen in the transition state of the isomerization was suggested to explain both the kinetic formation of the Z-enamine and the absence of exchange with deuteriated base during the isomerization. Quantum chemical calculations showed that the Z-carbanion (61) is actually more stable than the -carbanion (62). 

The kinetic behavior of the C2aH of 2-a-hydroxyethylthiazolium salts, including thiamin, was extensively reinvestigated in water by Stivers and Washabaugh using triiodide trapping rates of the enamine as a measure of the deprotonation rate constant. Based on the magnitude of the Bronsted constant, a diffusion-controlled reprotonation... 

Deprotonation to the enamine anion, selective coupling with the allylic terminus of dibromide 114, followed by an intramolecular enamine alkylation, afforded reduced isoquinoline 119. A rather elegant conversion to aminoaldehyde 122 ensued. Immonium ion formation in 119 via protonation with perchloric acid at first yielded the kinetic trans isomer, which underwent equilibration upon reflux in methanol to give the corresponding crystalline cis product 120. Diazomethane treatment led to aziridinium salt 121, which upon exposure to DMSO, ring opened with concomitant oxidation in a Komblum fashion to the aldehyde 122.63 Treatment with Lewis acid effected B-ring closure, thus... 

NMR and kinetic experiments have demonstrated that the reaction of nucleophiles, such as deprotonated / -diketones, enamines, and malonodinitrile, with PhCH=CHCO(R+) (R+ = l,3-Me2-2-azolium) proceeds via a Michael addition (rather than via a 1,2-addition followed by [3,3]-sigmatropic rearrangement). ... 

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