Conjugate Michael addition

Two-Group C-C Disconnections III 1,5-Difunctionalised Compounds Conjugate (Michael) Addition and Robinson Annelation... 

Q Predict the products of conjugate (Michael) additions, and show how to use these reactions in syntheses. Show the general mechanism of the Robinson annulation, and use it to form cyclohexenone ring systems. 

The reactions in this section cover the conjugate (Michael) addition of various lithiated nucleophiles to activated olefins such as enones and enoates. Lithium enolates are formed as intermediates during the addition process. They can be treated as such and trapped, for instance, by an electrophile to provide ketones or esters substituted both in the a and positions. We will focus only on the most important information relevant to the intermediate enolates, and those are rarely discussed in the literature on the Michael addition. The reader can advantageously consult Chapter 14 of the first part of this volume133, which is entirely dedicated to the organolithium additions to double bonds, for a more extensive coverage of the topic. 

Efforts directed towards the synthesis of stable, perhaps isolable, cyclopropenyl anions having three identical anion stabilizing groups, such as cyano or benzoyl, have been attempted without much success. Tricyanocyclopropene (22a) could not be prepared except as a transient intermediate which could be trapped with diphenylisobenzofuran The corresponding triketone (22b) was obtainable, but attempted generation of the corresponding anion was thwarted by conjugate (Michael) addition of the base to the double bond. The cyclopropenyl anion remains an illusive species ... 

Nucleophilic substitution at saturated carbon 20 Electrophilic addition to alkenes 22 Electrophilic aromatic substitution 29 Conjugate Michael addition of enolates 39 Radicals... 

The electrophilicity index also accounts for the electrophilic activation/deactivation effects promoted by EW and electron-releasing substituents even beyond the case of cycloaddition processes. These effects are assessed as responses at the active site of the molecules. The empirical Hammett-like relationships found between the global and local electrophilicity indexes and the reaction rate coefficients correctly account for the substrate selectivity in Friedel-Crafts reactions, the reactivity of carbenium ions, the hydrolysis of esters, the reactivity at the carbon-carbon double bonds in conjugated Michael additions, the philicity pattern of carbenes and the superelectrophilicity of nitronium, oxonium and carboxonium ions. This last application is a very promising area of application. The enhanced electrophilicity pattern in these series results from... 

The conjugate Michael addition of phosphonate-stabilized anions with dimethyl acetylenedicarboxylate has been described. For example, when the sodium salt of dimethyl l-(methoxycarbo-nyljmethylphosphonate is treated with dimethyl acetylenedicarboxylate, an (fij/CZ) mixture of two isomeric P.y-unsaturated phosphonates is isolated in modest yield (37%). ° Addition of enolates derived from diethyl 2-oxocycloalkylphosphonates to dimethyl acetylenedicarboxylate in aprotic conditions results in [n + 2] ring-expanded products in reasonable yields (Scheme 8.50). The reaction proceeds via a tandem Michael-aldol-fragmentation mechanism to give the ring enlarged products. 

Specific enolates by conjugate (Michael) addition An intermediate in Corey s ginkgolide synthesis A synthesis of jasmine ketolactone Tables of Enol Equivalents and Specific Enolates Modern Use of Specific Enolate Equivalents... 

Since conjugate (Michael) addition and Diels-Alder reactions use a,p-unsat united carbonyl compounds, asymmetric versions of these reactions could use the auxiliaries that we have seen in aldol reactions in the form of 118 and 119. Diels-Alder reactions work very well with these unsaturated amides and also with amides 121 derived from Oppolzer s chiral sultam14 120, prepared simply from camphorsulfonyl chloride. 

Group-transfer polymerization (GTP) was discovered by scientists at DuPont and involves the conjugate Michael addition of an enol silane or related compound to acrylate or methacrylate monomers under the influence of an activator. The process is related to anionic polymerization but the species involved are believed to feature a high degree of covalent character in the transition state for chain growth. 

An organocatalytic conjugate Michael addition of malonates to various ,/ -unsaturated aldehydes in the presence of an organocatalyst derived from proline in aqueous reaction media has been developed. The common feature of the modified 0 diaryl prohnol silyl ether catalysts (2) consist of long alkyl chains in their sttuctures. 

In addition to the radical amine-thiol-ene conjugation, the one-pot combination of aminolysis of a thiolactone unit and a nucleophilic thiol-ene conjugation (Michael addition) (Scheme 5, pathway b) was explored. The Michael addition between a nucleophile (e.g., thiol, amine, or stabilized carbanion) and an activated double bond (e.g., imidazole, acrylate, vinyl sulfone) is often the key step in polymer... 

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