Enolates conjugate addition with

The base removes the most acidic hydrogen, and the resulting enolate anion undergoes a conjugate addition with the Michael acceptor ... 

In a formal sense, the reaction of ascorbic acid (11) with various electrophiles may also be regarded as an intramolecular conjugate addition with subsequent alkylation of the intermediate enolate ion. For example, the reaction of 11 with ( )-2-methyl-2-butenenitrile afforded the natural product piptosidin (12), together with its di-epimer 1351. In a quite similar fashion, leucodrin (14) and delesserin (15) were prepared from the corresponding benzyl alcohols52. 

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. 

Rehearsal of the mechanism of a conjugate addition with an extended enolate. 

A useful technique to accomplish overall vicinal dialkylation of enones is to trap the enolate initially formed in the conjugate addition with TMS-Cl, and then regenerate the enolate under suitable conditions for its alkylation. Lithium 1-enolates of 3,5-dialkylcyclohexanones generated from the reaction of the corresponding TMS enol ethers with lithium amide in liquid ammonia-THF can be alkylated efficiently in liquid ammonia-THF, even with an unreactive alkylating agent such as n-butyl iodide (Scheme 10). ... 

Aluminum enolates can be formed by conjugate addition with diisobutylaluminum hydride (DIBAL-H) and a catalytic amount of methylcopper in a mixture of THF and HMPA (Scheme 28). " The role of copper and HMPA is crucial, for without these 1,2-reduction of the carbonyl group takes place. The effect of copper(l) on conjugate addition is not unexpected. In regard to the solvents it is suggested that HMPA functions not as a cosolvent but as an essential ligand. Treatment of an a. -un-saturated ketone with trimethylaluminum and a catalyst leads to a dimethylaluminum enolate with moderate ( )/(Z) selectivity. The (Z)-enolate reacts with diphenylketene to give another enolate (Scheme... 

Conjugate addition-dimerization reactions were also successfully accomplished within the tin(IV) enolate methodology, albeit in modest yields. Activated alkenes using two enone precursors formed conjugate addition products (Scheme 10). These conjugate additions with enone Michael acceptors provide a regiocontrolled route to bicyclic products. Because the enolate forms on the alkene side of the ketone, the reaction outcome can be predicted with some confidence. 

The three reactions are. enolization and trapping with silicon, direct addition with a hard irreversible nucleophile, and conjugate addition with a... 

The asymmetric conjugate addition of sulfur-based nucleophiles to Michael acceptors has been achieved using enantiomerically pure metal-based catalysts and organocatalysts. Sulfur nucleophiles are soft, and preferentially react by conjugate addition with a, p-unsaturated carbonyl compounds. Only catalytic amounts of the lithium thiolate (11.65) are required, since addition to the enone (11.66) generates the enolate (11.67). The enolate is then able to deprotonate thiol (11.68), regenerating thiolate (11.65) with formation of the product (11.69). 

Bromomalonate, selected as the pronucleophile, is proposed to undergo deprotonation by the diaryl prolinol catalysts lej to give the corresponding reactive enolate involved in the conjugate addition with different electron-poor alkenes (Scheme 7.9). The intramolecular alleviation proceeds with more nucleophilic indandione-derived enolate, under one-pot conditions, in... 

Acetal 136 on enolization followed by conjugate addition with nitro olefin 122 gave alkylated products 137 and 138 in a diastereomeric mixture of 10 1. Compound 137 was proceeded for amathaspiramide F synthesis, which on hydrolysis followed by N-trifluoroacetyl protection gave amide 139. Nitro group of compound 139 was converted into oxime 140. Hydrolysis of oxime followed by cyclization and then deprotection of N-trifluoroacetyl group gave amathaspiramide F (134) Scheme 12 [63],... 

When a stabilized enolate undergoes a 1,4-conjugate addition with an enone, it is called a Michael reaction. However, many related reactions with analogous mechanisms are also described as Michael additions. Any C=C double bond containing one or more EWGs is referred to as a Michael acceptor and soft nucleophiles that prefer 1,4-addition, including stabilized enolates and organocuprates, are described as Michael donors. ... 

With conjugated enones a carbon-carbon bond is formed by a Michael addition with concomitant formation of the proximal silyl enol ether (eq 4). In the presence of a Lewis acid, (1) undergoes conjugate additions with a,/3-unsaturated carbonyl compounds (eq 5). ... 

With certain other nucleophiles addition takes place at the carbon-carbon double bond rather than at the carbonyl group Such reactions proceed via enol intermediates and are described as conjugate addition ox 1 4 addition reactions... 

A synthetically useful reaction known as the Michael reaction, or Michael addition, involves nucleophilic addition of carbanions to a p unsaturated ketones The most common types of carbanions used are enolate 10ns derived from p diketones These enolates are weak bases (Section 18 6) and react with a p unsaturated ketones by conjugate addition... 

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