Enone , conjugate carbonyl Michael reactions

Conjugate addition to acyclic Michael acceptors. Sakurai and Hosomi (9, 445-446) reported one example of the fluoride ion-catalyzed reaction of allyltrimethylsilane with an acyclic enone. In that case (reaction with C6H5CH=CHCOCH,). 1.2- and 1,4-adducts are obtained in the ratio 2 1.1,4-Addition is enhanced by use of DMF and HMPT as solvent and by increase in the size of the group adjacent to the carbonyl group. 1,4-Addition is the main or predominant reaction with a,3-unsaturated esters or nitriles. In this case, it is superior to or competitive with allylation with lithium diallylcuprate. Yields in 1,4-additions to a,p-enones can compare favorably with those obtained with reactions catalyzed by TiC. ... 

The Michael reaction occurs with a wide variety of a,l3-unsaturated carbonyl compounds, not just conjugated enones. Unsaturated aldehydes, esters, nitriles, amides, and nitro compounds can all act as the electrophilic acceptor component in Michael reactions (Table 22.1). Similarly, a variety... 

Conjugate additions. Cyclopentaneacetic esters are readily prepared by cyclization of -iodo-a,P-unsaturated esters. The Michael reaction of silyl ketene acetals with enones (and Mukaiyama aldol reaction) can be promoted by Sml,. " However, thermodynamic enolsilylation of carbonyl compounds under similar conditions is noted. 

The addition at the p-position of an a,p-unsaturated carbonyl compound is described as conjugate addition, Michael addition, or 1,4-addition. It can be exemplified by the reaction in Figure 17.57, the addition of a cyanide ion to an enone. Students are often puzzled by the term 1,4-addition. Despite the way we usually write this mechanism, with the enolate anion being... 

Molecular orbital theory also predicts that a nucleophile of the sulfide type will bond at the carbon terminus of a conjugated ene carbonyl system that is, the nucleophile will bond with the electrophile in the Michael addition mode of reaction (20). Thus, the reaction of polysulfide dianion with an enone represented by a chalcone may proceed initially in such a manner as shown in Scheme 2, which reproduces one of the several pathways... 

Michael addition of metal enolates to a,/3-unsaturated carbonyls has been intensively studied in recent years and provides an established method in organic synthesis for the preparation of a wide range of 1,5-dicarbonyl compounds (128) under neutral and mild conditions . Metal enolates derived from ketones or esters typically act as Michael donors, and a,-unsaturated carbonyls including enoates, enones and unsaturated amides are used as Michael acceptors. However, reaction between a ketone enolate (125) and an a,/3-unsaturated ester (126) to form an ester enolate (127, equation 37) is not the thermodynamically preferred one, because ester enolates are generally more labile than ketone enolates. Thus, this transformation does not proceed well under thermal or catalytic conditions more than equimolar amounts of additives (mainly Lewis acids, such as TiCU) are generally required to enable satisfactory conversion, as shown in Table 8. Various groups have developed synthons as unsaturated ester equivalents (ortho esters , thioesters ) and /3-lithiated enamines as ketone enolate equivalents to afford a conjugate addition with acceptable yields. 

This adduct is in equilibrium with the stable enolate from the keto-ester and elimination now gives an unsaturated carbonyl compound. Such chemistry is associated with the aldol reactions we discussed in Chapter 27. The new enone has two carbonyl groups at one end of the double bond and is therefore a very good Michael acceptor (Chapter 29). A second molecule of enolate does a conjugate addition to complete the carbon skeleton of the molecule. Now the ammonia attacks either of... 

Reactions with Nucleophiles. As an enone tropone is readily susceptible to attack by nucleophiles in Michael-type reactions which might take place at any site in the ring. An early reported example was the formation of 2-aminotropone by reaction with either hydrazine or hydroxyl amine [169]. Reaction olsviously proceeds by conjugate attack (preferred over attack at the carbonyl group) followed by elimination of water or ammonia ... 

PROBLEM 19.98 The reaction titled Michael addition is also known as 1,4-addition or conjugate addition. Select the LUMO track of this reaction and notice the LUMO density of the starting a,P-unsaturated ketone (enone). Is there a large difference between the LUMO density at the P carhon and the carbonyl carbon Do you think that the nucleophile does 1,2- or 1,4-addition based on the orbital shown What controls the regioselectivity Which do you think would be a faster process, 1,2- or 1,4-addition Why ... 

Cinchona-alkaloid-catalysed conjugate cyanation of enones has enabled the synthesis of trifluoromethyl-substituted diarylpyrroles with ee<96%P° Thiochro-manes have been formed by asymmetric domino sulfa-Michael-aldol reactions of 2-mercaptobenzaldehyde with a,/ -unsaturated A-acylpyrazoles. Asymmetric organocatalysed oxy-Michael addition to y-hydroxy a,/ -unsaturated thioesters on reaction with t-BuCHO has been used to form -hydroxy carbonyl compounds HOCH2C H(OH)CH2CO.SAr via cyclic hemiacetal intermediates. 

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