Enolate ions extended

The present chapter extends our study of carbanions to the enolate ions derived from esters Ester enolates are important reagents m synthetic organic chemistry The stabilized enolates derived from p keto esters are particularly useful... 

The mechanism of dehydration is shown below (Fig.L). First of all, the acidic proton is removed and a new enolate ion is formed. The electrons in the enolate ion can then move in such a fashion that the hydroxyl group is expelled to give the final product, i.e. an a, p-unsaturated aldehyde. In this example, it is possible to change the conditions such that one gets the Aldol reaction product or the a, P-unsaturated aldehyde, but in some cases only the a, p-unsaturated carbonyl product is obtained, particularly when extended conjugation is possible. 

We have considered a variety of related intermediates in this chapter as extended versions of enolate ions 191 and as dienes. Another legitimate way to consider them is as acylated allyl anions 191c, and this leads us to the next chapter where we consider how to use allyl anions in synthesis. 

Addition to alk-4-yn-2-enoic csie extended enolate ions can be methylated C-4, and the products contain a conjugal ... 

In addition to enolate ions, other kinds of carbon nucleophiles add to a -unsaturated acceptors in the Michael reaction, greatly extending the usefulness and versatility of the process. Among the most important such nucleophiles are enaminea. Recall from Section 19.9 that enamines are readily prepared by reaction between a ketone and a secondary amine ... 

This is just a version of aldol condensation, where the nucleophile is the extended enolate ion at the y-carbon of an a, (3-unsaturated ketone, instead of the simple enolate at the a-carbon of a saturated ketone. 65. Work backward. 

The structure of mixed aggregates involving ester enolates is also of major interest to macromolecular chemists, since ionic additives are often introduced in the polymerization medium. The more stable arrangement between lithium 2-methoxyethoxide and MIB lithium enolate was thus calculated (at the DFT level) to be a 5 1 hexagonal complex with similar O—Li lateral coordinations212. The same team has recently extended this study to complexes formed between the same enolate in THF and a-ligands such as TMEDA, DME, 12-crown-4 and cryptand-2,1,1213. Only in the case of the latter ligand could a separate ion pair [(MIB-Li-MIB),2 THF]-, Li(2,l,l)+ be found as stable, still at the DFT level, as the THF solvated dimer [(MIB-Li)2,4 THF]. 

The true extended aldol reaction, the combination of an extended enolate in the y-position, with an aldehyde or ketone, can best be realised by combining a silyl enol ether 54 with an acetal 70 under Lewis acid catalysis.20 The Lewis acid, usually TiCl4, catalyses the formation of the oxonium ion 71 which adds in the y-position to the silyl enol ether [cf. 64] to give the adduct 72 from which the remaining OMe group can be removed with base to give the dienal 73, the extended aldol product. 

Acetylenic cobalt complexes greatly facilitate the heterolytic cleavage of adjacent alcohols or ethers. On treatment with Lewis acids, these complexes afford cobalt stabilized carbenium ions, which can be captured by nucleophiles such as enolates. Jacobi and Zheng have employed chiral boron enolates of Evans s oxa-zolidinone 6.91 (R = i-Pr). After removal of the chiral auxiliary, they obtained anti adds 11.43 with a high selectivity [1677] (Figure 11.9). The reaction can be extended to the boron enolates of related oxazolidinones and to a-branched propargyl derivatives. This reaction has been applied to the synthesis of P-aminoacids after Curtius rearrangement and oxidation of the triple bond [1677]. 

Enolates are powerful carbon nucleophiles and addition of enolates to carbonyl groups (aldol reactions) serve as a useful method for C-C bond formation. The Mukaiyama aldol reactions involving fluoride ion-promoted addition of silyl enolates to aldehydes are very popular and are frequently employed in the construction of carbon skeletons in organic synthesis [ 1 ]. The Mukaiyama aldol reaction with the silyl enol ether of cyclohexanone and 4-bromobenzaldehyde can be performed based on the electroosmotic flow (EOF) technique with a four-chaimel microstructured flow reactor (charmel dimensions 100 x 50pm). The reactor was prepared using a standard fabrication procedure developed at the University of Hull [2, 3]. Based on GC-MS analysis, quantitative conversion of the starting material was achieved in 20 min, whereas in the case with a traditional batch system a quantitative yield was obtained only when an extended reaction time of 24 h was employed (Figure 5.1). 

Mayr has extended his electrophilicity scale to benzaldehyde-derived iminium ions through measurement of rate constants for their reactions with C-nucleophiles such as enamines, silylated ketene acetals and enol ethers." With an E value of -9.27 for Ph-CH=NMe2" (in a range from -8.34 to -10.69 forpara-C j, andpura-OMe, respectively), these iminium ions are 10 orders more reactive than the parent aldehydes. However, the values are restricted to C-nucleophiles the iminium ions react 10 -10 times faster with water and amines than these E values would predict. Such reactions benefit from the anomeric stabilization of 0,Af-acetals and Af,Af-aminals. 

While effective methods for regiospecific conversion of silyl enol ethers such as 10 to enolate 9 (eq 3) further extended synthetic options using these basic intermediates, the observation that electrophilic reactions of silyl enol ethers (Friedel-Crafts-type chemistry via the intermediacy of siloxonium ion 11) were highly general enabled a new array of synthetic opportunities for carbonyl functionalization, often under essentially neutral conditions. ... 

We recall that enolates undergo condensation reactions with the carbonyl carbon atom of aldehydes (Section 21.7). Enolates tend to react to give alkylation at carbon. A similar reaction occurs between the phenolate ion and formaldehyde. Because both C-2 and C-4 are nucleophilic, two possible condensation products may result. The following reaction shows condensation at C-4, producing a conjugation-extended enolate. Subsequent tautomerization generates the enol form, which is a phenol. Solvent-mediated proton transfer also occurs, giving a phenoxide rather than the more basic (and less stable) alkoxide ion. 

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