Addition, conjugate diethyl malonate

Diethyl malonate adds to diethyl fumarate in a conjugate addition reaction promoted by sodium ethoxide in dry ethanol to give a tetraester, Diethyl fumarate is an excellent Michael acceptor because two ester groups withdraw electrons from the alkene, The mechanism involves deprotonation of the malonate, conjugate addition, and reprotonation of the product enolate by ethanol solvent, In this reaction two ester groups stabilize the enolate and two more promote conjugate addition. 

Stabilized anions exhibit a pronounced tendency to undergo conjugate addition to a p unsaturated carbonyl compounds This reaction called the Michael reaction has been described for anions derived from p diketones m Section 18 13 The enolates of ethyl acetoacetate and diethyl malonate also undergo Michael addition to the p carbon atom of a p unsaturated aldehydes ketones and esters For example... 

The reaction of the 2-pyridylvinyl ketone 28 with DMAD could take place in several ways, but nucleophilic attack from the nitrogen and Michael-type addition to the conjugated system gives the indolizine 30.251 A similar cyclization occurs with the diethyl malonate derivative 29 yielding 31, but in the case of 32 an unexpected rearrangement... 

Other 1,3-dicarbonyl compounds also exist largely in the enol form. In some examples there is an additional stabilizing factor, intramolecular hydrogen bonding. Diethyl malonate (diethyl propane-dioate) has a symmetrical enol stabilized by conjugation. The enol form is also stabilized by a very diethyl maionate favourable intramolecular hydrogen bond in a six-membered ring. 

Either the tertiary amine or the quaternary ammonium salt can be stored as a stable equivalent of the exo-methylene compound. In our first example, the Mannich base with dimethylamine is first methylated with methyl iodide and then added to the conjugate addition reaction. Elimination of trimethylamine, which escapes from the refluxing ethanol as a gas, reveals the exo-methylene ketone in which the methylene group is exo to a chain. Fast conjugate addition of the stabilized enolate of diethyl malonate produces the product. 

Dimedone has a trivial name because its preparation is so easy that it was discovered early in the history of organic chemistry. The first step is a conjugate addition of diethyl malonate to the unsaturated ketone mesityl oxide (4-methylpent-3-en-2-one given a trivial name for the same reason). Ethoxide ion is the base for the usual reason that nucleophilic substitution at the ester group simply regenerates starting material. 

An impressive alternate approach to the synthesis of furans beginning with alkynols was developed by Balme [160, 161] and subsequently applied in a total synthesis by Morimoto [162]. Balme discovered that a three-component coupling reaction between a propargylic alkoxide, a conjugate addition acceptor, and an unsaturated halide yields a variety of di- and trisubstituted furans. In one example, propargyl alcohol, diethyl ethoxymethylene malonate (193), and iodobenzene combine to furnish disubstituted furan 194 in... 

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. 

The 1,4- (conjugate) addition SBe pf carbon nucleophile to an a, 3-unsaturated carbonyl system is well known, usually reversible, and usually referred to as Michael addition. 83 Enolates and carbanions are common partners in Michael additions.The anion of diethyl malonate (534) reacts with MVK, for... 

The conjugate addition of an enolate to an a,/ -unsaturated carbonyl compound is called the Michael reaction or Michael addition. A good example is the following, where an enolate derived from diethyl malonate reacts with methyl vinyl ketone. 

In the late nineteenth century, Michael found that the enolate anion (46) derived from diethyl malonate reacts with ethyl acrylate at the P-carbon (as shown in the illustration) to give an enolate anion, 47, as the product. Remember from Chapter 22 (Section 22.7.4) that the a-proton of a 1,3-dicarbonyl compound such as diethyl malonate is rather acidic (pK of about 11), and even a relatively weak base will deprotonate to form the enolate anion. Michael addition of 46 with ethyl acrylate will give enolate anion 47, and aqueous acid workup leads to the isolated product, 48. Attack at the -carbon is possible because that carbon is less hindered than the acyl carbon, so reaction at the C=C unit is somewhat faster than attack at the acyl carbon. Michael addition occurs with relatively stable carbanion nucleophiles, such as malonate derivative 46 and some other common nucleophiles. Other conjugated carbonyl derivatives react similarly. 

Nucleophilic addition of enolate anions to o , 8-unsaturated carbonyl compounds was first reported in 1887 by the American chemist Arthur Michael. Following are two examples of Michael reactions. In the first example, the nucleophile adding to the conjugated system is the enolate anion of diethyl malonate. In the second example, the nucleophile is the enolate anion of ethyl acetoacetate. 

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