Carboxylic esters, conjugated reaction

Heterocyclic carboxylic esters (708) are as reactive as formate and acetate esters. Extended to 1-substituted biguanides, the reaction is promoted by metal alkoxides. Since the heterocyclic ring must be five-or six-membered and contains a conjugated system of double bonds, the reaction resembles formally that involving a,p-unsaturated esters (see below). Several successful examples are on record (599, 606). 

Tetraalkylammonium bromide was found to be a good catalyst for the conjugate addition of thiols to a,p-unsaturated nitriles, carboxylic esters, ketones, aldehydes, and nitro alkenes. The reactions proceeded rapidly and gave high yields of products (typically, 90%) (160). 

The reactions of protonated carboxylic esters in the absence of significant amounts of water have been discussed above. Two types of cleavage are possible. Alkyl-oxygen cleavage is a very fast reaction for the conjugate acids of tertiary alcohols... 

In contrast to the ester enolates, the a.O-carboxylic dianions are intrinsically more reactive and their use in conjugate reactions is thus limited. Typically, a-substituted-a.O-carboxylic dianions add exclusively to a,(3-unsaturated esters155a and nitroalkenes,155b while additions to ot,(3-enones are sensitive to the substitution pattern of the enones.155c>d Notable is the conjugate addition of dihydrobenzoic acid dianions (207), from Birch reduction of benzoic acids, to oi,3-unsaturated esters (Scheme 77).155e... 

Aldehydes, ketones, carboxylic esters, carboxylic amides, imines and N,A-disubstiluted hydrazones react as electrophiles at their s/ 2-hybridized carbon atoms. These compounds also become nucleophiles, if they contain an H atom in the a-position relative to their C=0 or C=N bonds. This is because they can undergo tautomerization to the corresponding enol as seen in Chapter 12. They are also C,H-acidic at this position, i.e., the H atom in the a-position can be removed with a base (Figure 13.1). The deprotonation forms the conjugate bases of these substrates, which are called enolates. The conjugate bases of imines and hydrazones are called aza enolates. The reactions discussed in this chapter all proceed via enolates. 

Conjugate hydrocyanation of oc -unsaturated carboxylic esters, acid chlorides, and acyl cyanides, is effected by reaction with diethylaluminium cyanide [e.g. (128) — (129)]. The acid chloride and cyanide are the most reactive. A double conjugate addition of nitromethane with a 2-methylene-4-en-3-one (130) gave a... 

In many of these cases, both the enolate anion and substrate can exist as (Z) or (E) isomers. With enolates derived from ketones or carboxylic esters. The (E) enolates gave the syn pair of enantiomers (p. 166), while (Z) enolates gave the anti pair. Nitro compounds add to conjugated ketones in the presence of a dipeptide and a piperazine. ° Malonate derivatives also add to conjugated ketones, and keto esters add to conjugated esters.Addition of chiral additives to the reaction, such as metal-salen complexes,proline derivatives, or (—)-sparteine, ... 

Aziridines. Aziridine-2-carboxylic esters are formed at room temperature by reaction of conjugated esters with NsONHCOOEt in the presence of CaO. Similarly, nitroalkenes react in the same way.- ... 

Rann et al. reported the dramatic influence of a new tailor-made, task-specific, and stable ionic liquid, butyl methyl imidazolium hydroxide ([bmim][OH]), in Michael addition. They have discovered that a task-specific ionic liqnid [bmim][OH] efficiently promoted the Michael addition of 1,3-dicarbonyl compounds, cyano esters, and nitro alkanes to a variety of conjugated ketones, carboxylic esters, and nitriles withont reqniring any other catalyst and solvent (Fig. 12.21) [16]. Very interestingly, all open-chain 1,3-dicarbonyl componnds such as acetylacetone, ethyl ace-toacetate, diethyl malonate, and ethyl cyanoacetate reacted with methyl vinyl ketone and chalcone to give the usual monoaddition products, whereas the same reactions with methyl acrylate or acrylonitrile provided exclusively bis-addition products. 

Ranu BC, Baneijee S (2005) Ionic liquid as catalyst and reaction medium. The dramatic influence of a task-specific ionic liquid, bmim][OH], in Michael addition of active methylene compounds to conjugated ketones, carboxylic esters, and nitriles. J Oig Lett 7 3049-3052... 

The ease of reaction depends both on the CH acidity of the addend and on the polarizability of the ethylenic double bond of the acceptor. Thus, in general, only such compounds function as addend in which a methylene or methine group is activated by two neighboring carbonyl or nitrile groups, as, for example, in malonic esters, malonodinitrile, cyanoacetic esters, 1,3-dioxo compounds and 3-oxo carboxylic esters, and their monoalkyl substitution products. The ethylenic double bond of the acceptor is polarized by conjugation with a polar multiple bond, so that the olefinic component is usually an unsaturated ketone, an, / -unsaturated ester, or an, / -unsaturated nitrile. The addition is catalysed by bases such as potassium hydroxide solution, sodium ethoxide, and amines. 

Addition-elimination. Axially chiral l,l -biphenyl-2-carboxylate esters are obtained by the reaction of 2-menthoxybenzoates with aryl Grignard reagents. Conjugate addition followed by elimination of a malonic ester unit constitutes a useful method for the access to (Z)-alkenes. The reagents are 1,1-dimetalloalkanes. 

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