Metalations enolates, lithium diisopropylamide

The most direct route towards functionalized aliphatic polyesters is based on the functionalization of polyester chains. This approach is a very appealing because a wide range of functionalized aliphatic polyesters could then be made available from a single precursor. This approach was implemented by Vert and coworkers using a two-step process. Eirst, PCL was metallated by lithium diisopropylamide with formation of a poly(enolate). Second, the poly(enolate) was reacted with an electrophile such as naphthoyl chloride [101], benzylchloroformate [101] acetophenone [101], benzaldehyde [101], carbon dioxide [102] tritiated water [103], ot-bromoacetoxy-co-methoxy-poly(ethylene oxide) [104], or iodine [105] (Fig. 26). The implementation of this strategy is, however, difficult because of a severe competition between chain metallation and chain degradation. Moreover, the content of functionalization is quite low (<30%), even under optimized conditions. 

A few comments concerning the crystallization of carbanions are in order. These comments are based upon the personal experience developed in our own laboratory and also upon observations noted in the literature in the course of crystallizing enolate anions. Although alkali metal enolate anions are relatively unstable compounds, they have been prepared in the solid state, isolated, and characterized by IR and UV spectroscopy in the 1970s. Thus the ot-lithiated esters of a number of simple esters of isobutyric acid are prepared by metallation of the esters with lithium diisopropylamide in benzene or toluene solution. The soluble lithiated esters are quite stable at room temperature in aliphatic or aromatic hydrocarbon solvents and are crystallized out of solution at low temperature (e.g. -70 °C.). Alternatively the less soluble enolates tend to precipitate out of solution and are isolated by centrifugation and subsequent removal of the solvent. Recrystallization from a suitable solvent can then be attempted. The thermal stability of the lithiated ester enolates is dramatically decreased in the presence of a solvent with a donor atom such as tetrahydrofuran. 

When the preparation of alkali metal enolates derived from alkanoylphosphonates was attempted by treatment with strong anhydrous bases such as lithium diisopropylamide or sodium hydride, the formation of phosphate phosphonate-type products was observed. This was interpreted in terms of fragmentation of the enolate formed in the first step to ketene and dialkyl phosphite anion (equation 75), and addition of the latter to the carbonyl group of an unreacted acylphosphonate molecules to form a bisphosphonate. Such molecules are known to rearrange to phosphate phosphonates ... 

Regioselective enolate formation using kinetic deprotonation of an unsymmetri-cal ketone has been discussed in Section 1.1.1. The specihc enolate can react with aldehydes to give the aldol product, initially formed as the metal chelate in aprotic solvents such as THF or EtiO. Thus, 2-pentanone, on deprotonation with lithium diisopropylamide (LDA) and reaction of the enolate with butanal, gave the aldol product 44 in reasonable yield (1.56). 

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