Conjugate addition of enolates

The product of a conjugate addition of an enolate or enol equivalent to an (X, 3-unsaturated carbonyl compound will necessarily be a dicarbonyl compound or an equivalent derivative. As the carbonyl group occupies such a central position in synthesis it will come as no surprise that these intermediates, with two carbonyl groups, are very widely used. 

The other important feature of this conjugate addition reaction is that the two carbonyl groups in the product are reasonably far apart while the newly formed bond is in the middle of the molecule. This means that Michael addition can be a convergent route to the product—a feature that usually maximizes synthetic efficiency. 

Conjugate addition of enoiates is the result of thermodynamic control 

Enolate nucleophiles have exactly the same opportunity to attack the carbonyl group directly as do the simple nucleophiles discussed in Chapter 10 and the same factors govern the eventual outcome 

We discussed the reason for this In Chapters 10 and 23. The main reason that the oohlugate addition product Is more atebte is that It has a C 0 group while the direct addition product has a C C group 

Introduction conjugate addition of enolates is a powerful synthetic transformation  

Oorgugate addition is also called Michael addition and is described in Chapters 10 and 23. 

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Conjugate addition of enolate anions to a, jS-unsaturated sulphoxides followed by a sulphoxide- ketone transformation were used for the preparation of 1,4-dicarbonyl compounds and cyclopentenone derivatives (equation 355)648. 

Schlessinger and coworkers described a conjugate addition of enolate species to ketene dithioacetal monoxides656 (equation 357). Some of the products obtained were elaborated to dihydrojasmone657, prostaglandins658 and rethrolones659. 

Thus, the dianion derived from a-amino acid substitutes the /1-chloride to give the ester of 2-(phenylsulfonyl)ethenyl amino acid and subsequent desulfonylation provides N-(benzoyl)vinylalanine methyl ester (62) (equation 61). The conjugate addition of enolates to methyl styryl sulfone (63) and subsequent intramolecular addition to the carbonyl moiety provide a synthetically valuable method for the construction of bicyclic and tricyclic skeletons52. Desulfonylation of the cyclization product 64 with sodium in ethanol-THF gives the diene 65 in good yield (equation 62). 

Conjugate addition of enolates under some circumstances can be carried out with a catalytic amount of base. All the steps are reversible. 

The conjugate addition of enolate anions onto a,P-unsaturated systems is an important synthetic reaction, and is termed the Michael reaction, though this terminology may often be used in the broader... 

Michael reaction conjugate addition of enolate anion onto unsaturated carbonyl... 

Conjugate addition of enolate anion to a, b-unsaturated carbonyl compounds is known as Michael addition. 

The titanium(IV) chloride-catalyzed conjugate addition of enol silyl ethers (182) to (184) and (189 Scheme 30), and silyl ketene acetals, (191) to (194), to ot, 3-enones is die key feature in various synthetic strategies (Mukaiyama-Michael) (Scheme 31).78 79 In contrast to the earlier described enolate addition... 

Mukaiyama-Michael reaction1 (13, 339-340 14, 344-345). The conjugate addition of enol silyl ethers of optically active ketones to a,(i-enones catalyzed by trityl perchlorate can proceed with high diastereoselectivity. Thus the (Z)-enol silyl ether (2) of the ketone (R)-l reacts with enone 3 to give the 1,5-ketone 4 with high... 

A. Bemardi, Stereoselective Conjugate Addition of Enolates to a,/3-Unsaturated Carbonyl Compounds , Gazz. Chim. ltd. 1995, 125, 539-547. 

Conjugate addition of enol silyl ethers can also be effected in this way.7 A similar reaction with dienol silyl ethers affords cyclized products. This variation of a Diels-Alder reaction can be useful because it can afford stereoisomers of the products formed by reactions catalyzed by conventional Lewis acids. 

Conjugate addition of enolate to a, p-unsaturated carbonyl compounds... 

Several problems in this chapter ask you to suggest ways to make molecules by conjugate additions of enols or enolates. We give one possible answer and sometimes comment on alternatives, but you should realize that there are many possible right answers to this sort of question. Make sure you have understood the principles behind each question and, if your answer is different from ours, check it with someone who knows. 

Revision of conjugate addition of enols (Chapter 29), another ring expansion with an enolate as leaving group, and an interesting piece of stereochemistry. 

Conjugate addition of enolate-type nucleophiles ch29 Reactions of heterocyclic aromatic compounds ch43... 

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