Silicon Michael addition

The controlled polymerization of (meth)acrylates was achieved by anionic polymerization. However, special bulky initiators and very low temperatures (- 78 °C) must be employed in order to avoid side reactions. An alternative procedure for achieving the same results by conducting the polymerization at room temperature was proposed by Webster and Sogah [84], The technique, called group transfer polymerization, involves a catalyzed silicon-mediated sequential Michael addition of a, /f-unsaluralcd esters using silyl ketene acetals as initiators. Nucleophilic (anionic) or Lewis acid catalysts are necessary for the polymerization. Nucleophilic catalysts activate the initiator and are usually employed for the polymerization of methacrylates, whereas Lewis acids activate the monomer and are more suitable for the polymerization of acrylates [85,86]. 

Rhodium(i) complexes are excellent catalysts for the 1,4-addition of aryl- or 1-alkenylboron, -silicon, and -tin compounds to a,/3-unsaturated carbonyl compounds. In contrast, there are few reports on the palladium(n) complex-catalyzed 1,4-addition to enones126,126a for the easy formation of C-bound enolate, which will result in /3-hydride elimination product of Heck reaction. Previously, Cacchi et al. described the palladium(n)-catalyzed Michael addition of ArHgCl or SnAr4 to enones in acidic water.127 Recently, Miyaura and co-workers reported the 1,4-addition of arylboronic acids and boroxines to a,/3-unsaturated carbonyl compounds. A cationic palladium(n) complex [Pd(dppe)(PhCN)2](SbF6)2 was found to be an excellent catalyst for this reaction (dppe = l,2-bis(diphenyl-phosphine)ethane Scheme 42).128... 

Group-transfer polymerizations make use of a silicon-mediated Michael addition reaction. They allow the synthesis of isolatable, well-characterized living polymers whose reactive end groups can be converted into other functional groups. It allows the polymerization of alpha, beta-unsaturated esters, ketones, amides, or nitriles through the use of silyl ketenes in the presence of suitable nucleophilic catalysts such as soluble Lewis acids, fluorides, cyanides, azides, and bifluorides, HF. ... 

The stability of an a-silyl carbanion is responsible for the unproved synthetic utility of the Stork annulation over other annulations195,196. These reactions involve the Michael addition of an enolate ion to an enone, and in the absence of a a-silyl substituent suffer drawbacks due to the reversibility of the Michael reaction. However, the addition of enolate ions to a-trimethylsilylvinyl ketones is not reversible, owing to a-silicon stabilization of the canonical form 152 shown in equation 122. 

MICHAEL ADDITIONS Alumina. Aluminum chloride. Cesium fluoride-Silicon(lV) cthoxidc. 1,4-Diazabicyclo[2.2.2]octanc. l,8-Diazabicyclo[5.4.0]-7-undecene. Ketene r-butyldimethylsilyl methyl acetal. Lithium acetylides. (S)-( + )-2-Mcthoxymethylpyrrolidine. Methyl lithiodithioacetate. Methyl (phcnylsulfinyl)acetate. Methyl 2-trimcthylsilylacrylate. Nickel carbonyl. Organocopper reagents. 8-Phenylmcnthol. Phenyl 2-(trimethylsilyl)ethynyl sulfone. Tetra-n-butylammonium fluoride. Tiianium(IV) chloride. 3-Triisopropylsilylpropynyllithiuni. Zirconium(IV) n-propoxiilc... 

Nucleophilic addition to vinylsilanes is facilitated by the fact that it leads to the formation of an anion which is a to silicon the anion is thus relatively stable. The reaction should be compared to the Michael addition, in which the anion generated is stabilized by an adjacent carbonyl group (Figure Si5.13). 

Because of the stability of iron tricarbonyl diene complexes, conjugated dienals are protected from polymerization when complexed, while other reactions can be carried out at the aldehyde functionaUty. A number of synthetically attractive nucleophilic transformations of the aldehyde can be performed on these complexes. These include, aldol reactions, Michael additions, reactions with organozinc, -silicon, -boron, and -tin... 

Although the silyl exchange should be typically intramolecular according to this associated mechanism, significant exchange between growing chains occurs during GTP. In order to account for this experimental observation. Quirk and coworkers proposed a dissociative mechanism, which relies on the dissociation of the pentacoordinat siliconate (49), followed by the Michael addition of the released enolate (50) onto the monomer... 

Acylation of a simple thiol with an alkyl carboxylate is not a very suitable method for preparation of S-alkyl thiocarboxylates. Transesterification is, however, possible if either the thiol or the carboxylic ester is activated. The enhanced reactivity of boron, aluminum and silicon thiolates has been utilized for the synthesis of a large variety of thiocarboxylic S-esters, including hydroxy derivatives (from lactones). a,P-Unsaturated thiol esters, e.g. cinnamoyl or 2-butenoyl derivatives, are also accessible. Michael addition, an undesirable side reaction of thiols, is completely avoided if alkyl trimethylsilyl sulfides ortris(arylthio)boranes are applied. ... 

Silicon-substituted cyclopropanes can also be generated by the reaction of electron-deficient alkenes with silyl-substituted carbanions bearing a leaving group. This transformation proceeds via sequential Michael addition and intramolecular ring closure (MIRC reaction). 

When MeNOa [233a] and DMSO [81] are used as solvents, Michael addition of KSA proceeds smoothly at room temperature without additional catalyst. Coordination of the solvent molecule to the silicon atom would enhance the nucleophilicity of KSA to effect the uncatalyzed reaction. 

The second possible mechanism has, for example, been proposed for the Michael addition performed in heterogeneous conditions. It postulates the activation of a silyl enol ether by F" with formation of pentacoordinated silicon in a pre-equilibrium, followed by concerted attack of the Michael acceptor in the rate-determining step giving a hexa-coordinate intermediate169 (Scheme 24). 

The use of silicon carbide inserts has proved valuable in the uncatalyzed aza-Michael addition between piperazine and methyl acrylate. The reaction was low yielding using pure toluene as the solvent since the maximum temperature that could be attained was 170 °C. Adding the passive heating elements to the reaction mixture allowed for temperatures of 200 °C to be reached and, with this, a dramatic increase in the yield for the reaction was observed (Scheme 2.10). The product isolation procedure was trivial and consisted of physical removal of the heating element using a pair of tweezers followed by removal of the solvent. 

Scettri et al. reported the aza-Michael addition of aniline to chalcones under solvent-free conditions, promoted by cinchonine. The corresponding products were obtained in good yield but with poor ee (11-58%). The enantioselectivity was improved up to 99% by the addition of an achiral silicon-based Lewis acid catalyst such as trimethylsilyl iodide (TMSI). ... 

The highly electrophilic cationic bis(8-quinolinolato)aluminum complex 407 enabled Yamamoto and coworkers to perform Mukaiyama-Michael additions of silyl enol ethers to crotonylphosphonates 406. The procedure was not only applicable to enol silanes derived from aryl methyl and alkyl methyl ketones (a-unsubstituted silicon enolates) but also to several cycfic a-disubstituted silyl enol ethers, as illustrated for the derivatives of a-methyl tetralone and indanone 405 in Scheme 5.105. Despite the steric demand of that substitution pattern, the reaction occurred in relatively high chemical yield with varying diastereoselectivity and excellent enantiomeric excess of the major diastereomer. The phosphonate residue was replaced in the course of the workup procedure to give the methyl esters 408. The protocol was extended inter alia to the silyl enol ether of 2,6,6-tetramethylcyclohexanone. The relative and absolute configuration of the products 408 was not elucidated [200]. 

If a Michael reaction uses an unsymmetrical ketone with two CH-groups of similar acidity, the enol or enolate is first prepared in pure form (p. llff.). To avoid equilibration one has to work at low temperatures. The reaction may then become slow, and it is advisable to further activate the carbon-carbon double bond. This may be achieved by the introduction of an extra electron-withdrawing silyl substituent at C-2 of an a -synthon. Treatment of the Michael adduct with base removes the silicon, and may lead as well to an aldol addition (G. Stork, 1973, 1974 B R.K. Boeckman, Jr., 1974). 

Classical C,C-coupling reactions of AN anions (Henry, Michael, and Mannich) involve complex systems of equilibria and, consequently, generally not performed in protic solvents. The introduction of the silyl protecting group allows one to perform these reactions in an aprotic medium to prepare or retain products unstable in the presence of active protons. In addition, the use of nucleophiles which are specifically active toward silicon (e.g., the fluoride anion) enables one to design a process in which the effective concentration of a-nitro carbanions is maintained low. 

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