Michael Additions of Stabilized Anions

Stabilized anions exhibit a pronounced tendency to undergo conjugate addition to a, 3-unsaturated carbonyl compounds. This reaction, called the Michael reaction, has been described for anions derived from p-diketones in Section 18.13. The enolates of ethyl acetoacetate and diethyl maionate also undergo Michael addition to the p-carbon atom of a,p-unsaturated aldehydes, ketones, and esters. For example. 

In this reaction the enolate of diethyl maionate adds to the p carbon of methyl vinyl ketone. 

---

Conjugate addition of stabilized anions, Michael reaction... 

Functionalized cyclopropyl derivatives can be prepared via Michael addition of carbon nucleophiles carrying a leaving group at the a-carbon followed by intramolecular substitution as depicted in equation 125. Anion-stabilizing a-substituents in the nucleophiles... 

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 ... 

The use of diethyl l-(ethoxycarbonyl)vinylphosphonate is based on Michael addition of anionic nucleophiles to the double bond to produce stabilized phosphonate anions capable of undergoing subsequent alkenylation reaction with aldehydes or ketones by a Homer-Wadsworth-Emmons process (Scheme 8.27)." 2 " "... 

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. 

The first one can be described as the Michael addition of the N-aUylamine 208 to an acceptor-substituted triple bond of209 to form an intermediate N-allyl enammonium enolate 210 (alkyne carbonester Claisen rearrangement). The anion stabilizing group... 

The TT-allylpalladium complexes 241 formed from the ally carbonates 240 bearing an anion-stabilizing EWG are converted into the Pd complexes of TMM (trimethylenemethane) as reactive, dipolar intermediates 242 by intramolecular deprotonation with the alkoxide anion, and undergo [3 + 2] cycloaddition to give five-membered ring compounds 244 by Michael addition to an electron-deficient double bond and subsequent intramolecular allylation of the generated carbanion 243. This cycloaddition proceeds under neutral conditions, yielding the functionalized methylenecyclopentanes 244[148], The syn-... 

The Knoevenagel reaction has many similarities to the Michael addition, in which a base is required to form a carbanion Ifom an activated methylene precursor which subsequently undergoes nucleophilic addition to an alkene containing a group such as an ester capable of stabilizing the resulting anion by delocalization. These reactions are widely used for... 

Silylcuprates have been reported to undergo reactions with a number of miscellaneous Michael acceptors [65]. Conjugate addition to 3-carbomethoxy acyl pyri-dinium salts [65a] affords 4-silyl-l,4-dihydropyridines. Oxidation with p-chlorand generates a 4-acyl pyridinium salt that gives the 4-silylnicotinate upon quenching with water, and methyl 4-silyl-2-substituted dihydronicotinates upon quenching with nucleophiles (nucleophilic addition at the 6-position). The stabilized anion formed by conjugate addition to an a, j8-unsaturated sulfone could be trapped intramolecularly by an alkyl chloride [65b]. 

Michael additions to benzotriazole-stabilized carbanions have been reviewed. review of the structural dependence of heterolytic bond dissociation energy of carbon-carbon a-bonds in hydrocarbons has summarized the synthesis and behaviour of molecules in which highly stable cationic and anionic hydrocarbon moieties have apparently been combined. 

A limited number of other anionic species have been employed as Michael donors in tandem vicinal difunctionalizations. In a manner similar to sulfur ylides described above, phosphonium ylides can be used as cyclopropanating reagents by means of a conjugate addition-a-intramolecular alkylation sequence. Phosphonium ylides have been used with greater frequency261-263 than sulfur ylides and display little steric sensitivity.264 Phosphorus-stabilized allylic anions can display regiospecific 7-1,4-addition when used as Michael donors.265... 

Organolithiums have been shown to add to a variety of trithiocarbonate oxides exclusively in a thiophilic maimer, as a consequence of the electrophilic character of the sulfine sulfur, to give an intermediate carbanion stabilized by three sulfur atoms the soft carbanion, which forms trithioorthoester oxide on quenching with water, acts as the equivalent of the (alkylthio)carbonyl anion in Michael addition.98... 

One potential problem in the reactions of stabilized allylic or propargylic carb-anions is the dimerization of the starting material if the carbanions are not formed stoichiometrically. Alkenes substituted with electron-withdrawing groups are good Michael acceptors, to which nucleophiles will undergo conjugate addition. For instance, the Baylis-Hillman reaction of allyl cyanide with benzaldehyde requires careful optimization of the reaction conditions to avoid dimerization of the nitrile (Scheme 5.12). This problem is related to a common side reaction of Michael additions reaction of the product with the Michael acceptor (Scheme 10.21). 

The use of heteroaryl vinyl sulfides and vinyl dithiocarbamates (166) as hetero-Michael addition acceptors has been described. Combined chelating and electron-withdrawing effects were postulated to stabilize the transient anionic species and allow smooth Michael-induced ring closure to produce C-glycosides (167).191... 

---