What Is the Michael Reaction

Enzyme atalyzed reduction of the thioester group of 3-hydroxy-3-methylglutaryl-CoA to a primary alcohol gives mevalonic acid, shown here as its anion  

Thus far, we have used carbon nucleophiles in two ways to form new carbon—carbon bonds  

Addition of organomagnesium (Grignard) reagents to the carbonyl groups of aldehydes, ketones, and esters. 

Addition of an enolate anion to a carbon—carbon double bond conjugated with a carbonyl group presents an entirely new synthetic strategy. In this section, we study a type of conjugate addition involving nucleophrhc addition to an electrophrhc double bond. 

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Condensations Invoived in Biological Processes What Is the Michael Reaction CHEMICAL CONNECTIONS ... 

Notice that the compound we have just made has a 1, 5( ) relationship between the two carbonyl groups. This is an example of the Michael reaction. Here is another suggest what the product would be. 

What is the origin of the catalytic activity and the mode of enantioselection of the LSB-catalyzed Michael reactions To clarify the interaction between the enone and the chiral... 

The decarboxylation reaction usually proceeds from the dissociated form of a carboxyl group. As a result, the primary reaction intermediate is more or less a carbanion-like species. In one case, the carbanion is stabilized by the adjacent carbonyl group to form an enolate intermediate as seen in the case of decarboxylation of malonic acid and tropic acid derivatives. In the other case, the anion is stabilized by the aid of the thiazolium ring of TPP. This is the case of transketolases. The formation of carbanion equivalents is essentially important in the synthetic chemistry no matter what methods one takes, i.e., enzymatic or ordinary chemical. They undergo C—C bond-forming reactions with carbonyl compounds as well as a number of reactions with electrophiles, such as protonation, Michael-type addition, substitution with pyrophosphate and halides and so on. In this context,... 

Treatment with a base results in the ehmination of the alcohol at the 5 position by what is in effect a reverse Michael reaction to give the enone (19-1). The additional... 

Intermolecular Michael reactions continue to be developed. Karl Anker Jorgensen of Aarhus University, Denmark, has found (Angew. Chem. Ini. Ed. 2004,43, 1272) that the organocatalyst 3 mediates the addition of 2 to 1 with high enantiomeric excess. What is more, under the reaction conditions the intial Michael addition is followed by an aldol condensation, to give 4 as essentially a single diastereomer. 

The situation with stabilized ylides is rather different from that with unstabilized ones because the formed product has the potential to imdergo Michael addition to the corresponding C-glycoside. It is not clear what factors control the question of cyclization selectivity, but it is certain that reaction conditions and substrate structure both play an important role for the reaction in question. 

Lithium enolates do not even solve all problems of chemoselectivity most notoriously, they fail when the specific enolates of aldehydes are needed. The problem is that aldehydes self-condense so readily that the rate of the aldol reaction can be comparable with the rate of enolate formation by proton removal. Fortunately there are good alternatives. Earlier in this chapter we showed examples of what can go wrong with enamines. Now we can set the record straight by extolling the virtues of the enamines 96 of aldehydes.17 They are easily made without excessive aldol reaction as they are much less reactive than lithium enolates, they take part well in reactions such as Michael additions, a standard route to 1,5-dicarbonyl compounds, e.g. 97.18... 

Poly(propylene imine) (PPI or POPAM) dendrimers are the first dendritic stmctures found in literature. They were first reported by Buhleier etal, who presented a divergent synthesis of branched and dendritic-like molecules. These simple structures were accomplished using controlled organic chemistry. In this case, a Michael reaction between a primary amine and two equivalents of acrylonitrile resulted in a dinitrile. Further reduction through Co(II)-catalyzed hydrogenolysis led to a terminal diamine (Figure 16). An iterative protocol allowed the con-stmction of what today is defined as a second-generation... 

Recall that nucleophiles don t ordinarily add to carhon—carbon double bonds. Rather, they add to electrophiles (Section 5.2). What activates a carbon-carbon double bond for nucleophilic attack in a Michael reaction is the presence of the adjacent carbonyl group. One important contributing structure of a,jS-unsaturated carbonyl compounds puts a positive charge on the )3-carhon of the double bond, making it electrophilic in its reactivity ... 

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