Alkoxide Michael-type addition

In the epoxidation process (Figure 4.4), the oxygen of the enone s carbonyl function first coordinates with the zinc atom. The ethylperoxy anion then attacks the (3-position, which constitutes a Michael-type addition. The subsequent cyclization gives the epoxy ketone and the zinc alkoxide. 

Interception of the cr-adduct with an external hydride source, leading to an overall Michael-type addition is a synthetically useful variation of the Heck reaction (see Sect. IV.2.5), But there are also examples of a--intermediates that are relatively stable toward elimination due to chelation. One such intermediate as reported by Cheng and Daves Jr. is shown in Scheme 31.This isolated complex underwent j8-elimination of hydrogen, flnfi-alkoxide elimination, and replacement by hydrogen in addition to anfi-elimination of acetate, depending on the conditions used. 

The Michael-type conjugate addition of an alkoxide such as methoxide to an a,p-unsaturated nitrile or aldehyde proceeds in solution quite readily, being complete in 5—10 minutes. In the gas phase however, it was found that reaction (6a) does not occur there is no evidence of the addition product even at the longest trapping times, nor in the unquenched mode. Rather, the sole product observed is due to proton loss from the nitrile, to form a nominal vinyl anion, reaction (6b). 

In the above reaction one molecular proportion of sodium ethoxide is employed this is Michael s original method for conducting the reaction, which is reversible and particularly so under these conditions, and in certain circumstances may lead to apparently abnormal results. With smaller amounts of sodium alkoxide (1/5 mol or so the so-called catal3rtic method) or in the presence of secondary amines, the equilibrium is usually more on the side of the adduct, and good yields of adducts are frequently obtained. An example of the Michael addition of the latter type is to be found in the formation of ethyl propane-1 1 3 3 tetracarboxylate (II) from formaldehyde and ethyl malonate in the presence of diethylamine. Ethyl methylene-malonate (I) is formed intermediately by the simple Knoevenagel reaction and this Is followed by the Michael addition. Acid hydrolysis of (II) gives glutaric acid (III). 

The Michael reaction is the conjugate addition of a soft enolate, commonly derived from a P-dicarbonyl compound 24, to an acceptor-activated alkene such as enone 41a, resulting in a 1,5-dioxo constituted product 42 (Scheme 8.14) [52]. Traditionally, these reactions are catalyzed by Bronsted bases such as tertiary amines and alkali metal alkoxides and hydroxides. However, the strongly basic conditions are often a limiting factor since they can cause undesirable side- and subsequent reactions, such as aldol cyclizations and retro-Claisen-type decompositions. To address this issue, acid- [53] and metal-catalyzed [54] Michael reactions have been developed in order to carry out the reactions under milder conditions. 

The Michael reaction takes place with a wide variety of a, 8-unsaturated carbonyl compounds as well as with o ,j3-unsaturated nitriles and nitro compounds. The most commonly used types of nucleophiles in Michael reactions are summarized in Table 19.1. The bases most commonly used to generate the nucleophile are metal alkoxides, pyridine, and piperidine. It is important to realize that other nucleophiles can undergo similar additions to the beta carbon of unsaturated carbonyl compounds (e.g., amines, alcohols, and water). 

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