Silyl anions ethers

Silyl enol ethers are other ketone or aldehyde enolate equivalents and react with allyl carbonate to give allyl ketones or aldehydes 13,300. The transme-tallation of the 7r-allylpalladium methoxide, formed from allyl alkyl carbonate, with the silyl enol ether 464 forms the palladium enolate 465, which undergoes reductive elimination to afford the allyl ketone or aldehyde 466. For this reaction, neither fluoride anion nor a Lewis acid is necessary for the activation of silyl enol ethers. The reaction also proceed.s with metallic Pd supported on silica by a special method[301j. The ketene silyl acetal 467 derived from esters or lactones also reacts with allyl carbonates, affording allylated esters or lactones by using dppe as a ligand[302]... 

The combination of silyl enol ethers and fluoride ion provides more reactive anions to give alkylated nitre compounds in good yields after oxidation v/ith DDQ, as shovm in Eq. 9.22. This process provides a new method for synthesis of indoles and oxyindoles fsee Chapter 10, Symhesis of Hatarocydic Compoioids). 

The reactivity pattern (1) of silyl enol ethers and ketene acetals is based largely on their synthetic equivalence to enolate anions. Recently, a different spectrum of behaviour has been revealed, particularly in those reactions that involve direct reaction without prior generation of the enolate anion. Indeed, the historic development of silyl enol ethers can be seen in three separate phases, involving... 

The focus of Chapters 1 and 2 is enolates and related carbon nucleophiles such as silyl enol ethers, enamines, and imine anions, which can be referred to as enolate equivalents. 

The aldol reactions introduced thus far have been performed under basic conditions where enolate species are involved as the reactive intermediate. In contrast to the commonly accepted carbon-anion chemistry, Mukaiyama developed another practical method in which enol species can be used as the key intermediates. He is the first chemist to successfully demonstrate that acid-catalyzed aldol reactions using Lewis acid (such as TiCU) and silyl enol ether as a stable enol equivalent can work as well.17 Furthermore, he developed the boron tri-fluoromethane sulfonate (triflate)-mediated aldol reactions via the formation of formyl enol ethers. 

An interesting pericyclic-anionic-pericyclic domino reaction showing a high stereoselectivity is the cycloaddition-aldol-retro-ene process depicted in scheme 20.1581 The procedure presumably starts with a [4+2]-cycloaddition of diene 98 and S02 in presence of a Lewis acid. After opening of the formed adduct reaction with (Z)-silyl vinyl ether 99 leads to a mixture of alk-2-enesulfinic acids 101. It follows a retro-ene reaction which affords a 7 3 mixture of the products 102 and 103. The reaction described by Vogel et al is a nice example for the efficient generation of polypropionate chains with the stereoselective formation of three stereogenic centers and one (0-double bond in a three-component domino reaction in its strict definition. 

Retro-Brook rearrangement of the [l,3]-variant will readily take place in sp and sp carbanion systems. Kuwajima and Takeda and Corey and Rticker have developed the [l,3]-retro-Brook rearrangement of silyl enol ether anions which provide a-silyl ketones (equation 100 and 101). 

Lithium Enolates. The control of mixed aldol additions between aldehydes and ketones that present several possible sites for enolization is a challenging problem. Such reactions are normally carried out by complete conversion of the carbonyl compound that is to serve as the nucleophile to an enolate, silyl enol ether, or imine anion. The reactive nucleophile is then allowed to react with the second reaction component. As long as the addition step is faster than proton transfer, or other mechanisms of interconversion of the nucleophilic and electrophilic components, the adduct will have the desired... 

Alkylation or acylation of ketones, sulfides, and amines. This reagent generally reacts with alcohols or carboxylic acids to form 2,2,2-trifluoroethyl ethers or esters in satisfactory yields, except in the case of alcohols prone to dehydration. The reaction of these ethers provides a simple synthesis of unsymmctrical sulfides (equation I). A similar reaction can be used for preparation of secondary amines or amides (equation II). Enolatc anions (generated from silyl cnol ethers with KF) can be alkylated or acylated with a or b (equation III). Use of Grignard reagents in this type of coupling results in mediocre yields. 

Fluoride ion-catalysed addition of trifluoromethyltrimethylsilane to acyl silanes occurs to give l,l-difluoro-2-trimethylsilyloxyalkenes (silyl enol ethers of difluoromethyl ketones), through nucleophilic addition of trifluoromethyl anion, Brook rearrangement and loss of fluoride. These compounds could be isolated when tetrabutylammonium difluorotriphenylstannate was used as a catalyst use of tetrabutylammonium fluoride gave the product corresponding to subsequent aldol reaction with the difluoromethyl ketone (Scheme 78)m. 

Homologated (E)-unsaturated carboxylic acids The anion (2) of 1, formed with LDA in THF at — 50°, is alkylated exclusively at the /-position. The products (3) are converted into a,/S-unsaturated acids (4) on oxidation and thermolysis. This behavior contrasts with that of the anion of the corresponding silyl enol ether, CH3SCH2CH=C(CN)OSi(CH3)3, which undergoes exclusively a-alkylation.2... 

Addition of a silylating reagent such as Me3SiCl to the reaction mixture traps the enolate anions and produces two silyl enol ethers in a ratio which reflects the ratio of the enolate anions. Thus if 2-methylcyclohexanone is added to the hindered base LDA at -78 °C and the mixture stirred for 1 hour at -78 °C and quenched with MeySiCl, then the major product is the silyl enol ether derived from the kinetic enolate. In contrast, heating 2-methylcyclohexanone, triethylamine, and Me3SiCl at 130 °C for 90 hours... 

For example, addition of the anion of phenyl ethyl sulphone to benzyl trimethylsilyl ketone gives a silyl enol ether by the pathway depicted in Figure Si6.8. 

From these observations, Woerpel and Cleary proposed a mechanism to account for allylic silane formation (Scheme 7.23).85 Silacyclopropane 94 is formed from cyclohexene silacyclopropane 58 through silylene transfer. Coordination of the Lewis basic benzyl ether to the electrophilic silicon atom86-88 generates pentacoordinate siliconate 95 and increases the nucleophilicity of the apical Si-C bond.89 Electrophilic attack by silylsilver triflate 96 forms silyl anion 97. Intramolecular deprotonation and elimination then affords the silylmethyl allylic silane. 

The functionalized silyl enol ethers 156 are useful synthetic intermediates since electrophiles can now be introduced either directly in the P-position by known methodology 55) or in the opposition after deprotonation with LDA to an allyl anion (Eq. 70)61>. Both pathways should enormously widen the scope of specifically substituted y-oxoesters and their derivatives obtained via siloxycyclopropanes. 

Sensible choice of an appropriate specific enol equivalent will allow almost any aldol reaction to be performed successfully. The first two compounds in our list, the silyl enol ethers and the lithium enolates, have a specially wide application and we should look first at the way these work. As the table suggests, silyl enol ethers are more like enols they are nonbasic and not very reactive. Lithium enolates are more like enolate anions they are basic and reactive. Each is appropriate in different circumstances. 

The answer is both For the Li enolate, the usual rule makes OU of lower priority than oMe, so it s E, while the silyl enol ether (or silyl ketene acetal ) has OSi of higher priority than OMe, so it s Z. This is merely a nomenclature problem, but it would be irritating to have to reverse all our arguments for lithium enolates simply because lithium is of lower atomic number than carbon. So, for the sake of consistency, it is much better to avoid the use of Eand Z with enolates and instead use cis and trans, which then always refer to the relationship between the substituent and the anionic oxygen (bearing the metal). 

When the acetal and the silyl enol ether are mixed with the same Lewis acid catalyst, Noyori found that an efficient aldol-style condensation takes place with the acetal providing the electrophile. The reaction is successful at low temperatures and only a catalytic amount of the Lewis acid is needed. Under these conditions, with no acid or base, few side-reactions occur. Notice that the final desilylation is carried out by the triflate anion to regenerate the Lewis acid Me3Si-OTf. Triflate would be a very poor nucleophile for saturated carbon but is reasonable for silicon because oxygen is the nucleophilic atom. 

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