Stereochemistry ester anions

VinylpyridineS. The stereochemistry of anionic polymerization of 2-vinylpyridine is predominantly isotactic for most polymerization conditions as shown by the data in Table 14 (166). The coordination of the penultimate psrridyl nitrogen with the magnesium ester enolate at the chain end has been invoked to... 

The alkylation reactions of enolate anions of both ketones and esters have been extensively utilized in synthesis. Both very stable enolates, such as those derived from (i-ketoesters, / -diketones, and malonate esters, as well as less stable enolates of monofunctional ketones, esters, nitriles, etc., are reactive. Many aspects of the relationships between reactivity, stereochemistry, and mechanism have been clarified. A starting point for the discussion of these reactions is the structure of the enolates. Because of the delocalized nature of enolates, an electrophile can attack either at oxygen or at carbon. 

Stereoinversion Stereoinversion can be achieved either using a chemoenzymatic approach or a purely biocatalytic method. As an example of the former case, deracemization of secondary alcohols via enzymatic hydrolysis of their acetates may be mentioned. Thus, after the first step, kinetic resolution of a racemate, the enantiomeric alcohol resulting from hydrolysis of the fast reacting enantiomer of the substrate is chemically transformed into an activated ester, for example, by mesylation. The mixture of both esters is then subjected to basic hydrolysis. Each hydrolysis proceeds with different stereochemistry - the acetate is hydrolyzed with retention of configuration due to the attack of the hydroxy anion on the carbonyl carbon, and the mesylate - with inversion as a result of the attack of the hydroxy anion on the stereogenic carbon atom. As a result, a single enantiomer of the secondary alcohol is obtained (Scheme 5.12) [8, 50a]. 

The formation of cyclopropanes from 7C-deficient alkenes via an initial Michael-type reaction followed by nucleophilic ring closure of the intermediate anion (Scheme 6.26, see also Section 7.3), is catalysed by the addition of quaternary ammonium phase-transfer catalysts [46,47] which affect the stereochemistry of the ring closure (see Chapter 12). For example, equal amounts of (4) and (5) (X1, X2 = CN) are produced in the presence of benzyltriethylammonium chloride, whereas compound (4) predominates in the absence of the catalyst. In contrast, a,p-unsatu-rated ketones or esters and a-chloroacetic esters [e.g. 48] produce the cyclopropanes (6) (Scheme 6.27) stereoselectively under phase-transfer catalysed conditions and in the absence of the catalyst. Phenyl vinyl sulphone reacts with a-chloroacetonitriles to give the non-cyclized Michael adducts (80%) to the almost complete exclusion of the cyclopropanes. 

Now comes the key step intramolecular conjugate addition of the nitroalkane anion to the unsaturated ester. When catalysed by CsF and a tetra-alkyl ammonium salt, this is selective (1.5 1) for the all equatorial products 100. Reduction and cyclisation give the lactam 102 having the right stereochemistry for (Llycorane 72. 

While scission of the three bonds a to the ester in 2 provides a very rich bounty of stabilised anion/electrophile partnerships, a detailed evaluation of each respective forward reaction reveals that only one is tactically viable. For example, the cleavage of bond a in 2 would not be strategic for it would require enolate 11 to undergo methylation from its more hindered top-face (Scheme 12.2), which would be most unlikely. Such a plan would almost certainly lead to a product with incorrect stereochemistry at the newly introduced quaternary carbon centre. In similar... 

The first step is conjugate addition of the highly stabilized anion. The intermediate enolate then closes the three-membered ring by favourable nucleophilic attack on the allylic carbon. The leaving group is the sulfinate anion and the stereochemistry comes from the most favourable arrangement in the transition state for this ring closure. The product is the methyl ester of the important chrysan-themic acid found in the natural pyrethrum insecticides. 

Using the chiral ester X as a starting material, draw the carboxylate anion and alcohol formed (including stereochemistry) from hydrolysis of X via the accepted mechanism (having a tetrahedral intermediate) and the one-step Sn2 alternative. Given that only one alcohol, (R)-2-butanol, Is formed in this reaction, what does this indicate about the mechanism ... 

The strong base is necessary in the cyclization because no stable enolate can be formed ftorr. product. In other acylations of esters by esters the product has at least one hydrogen atom or carbon atom between the two carbonyl groups and forms a stable enolate under the reaj conditions. There are several examples in the chapter and the answer to Problem 3 makes a sp. point of this. The strong base is needed to convert one of the esters completely into its enofi i The stereochemical point is that one of the esters becomes an enolate and so lose stereochemistry but the other must be pointing inwards for cycUzation to occur. This can happer reversible formation of the enolate anion. 

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