Synthetic equivalents silyl enol ethers

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... 

According to results published by Fer6zou and coworkers, the iV,iV-diisopropylcarba-moyl group of homoaldol adducts can be directly attacked by slim nucleophiles such as lithium ethynylide or excess methyllithium (equation 98) . The TIPS ether 359 was treated with three equivalents of methyllithium to yield [via the (Z)-enolate 360] the aldehyde 361. Trapping of 360 by TBSCl gives rise to the synthetically valuable (Z)-silyl enol ether 362. 

Silyl enol ethers (Figure Si3.1) are stable molecules which may be isolated, purified, and characterized using standard organic procedures. As will be illustrated below, they are sources of regiochemically-pure enolate ions and their equivalents, and as such they play an important role in modern synthetic organic chemistry. 

According to Section 12.3 enamines are just one synthetic equivalent for enols that are not sufficiently represented in equilibrium with a carhonyl compound to allow for a-functional-izations. Enol ethers and silyl enol ethers, which are addressed in this section, are other synthetic equivalents for such enols. An enol ether, for example, is used as an enol equivalent for aldehyde enols, since several aldehydes do not form stable enamines. In addition, enol ethers or silyl enol ethers are usually employed as synthetic equivalents for the enols of ,/i-unsatu-rated carbonyl compounds. The attempt to react ce,/ -unsaturated carhonyl compounds with secondary amines to give a dienamine is often frustrated by a competing 1,4-addition of the amine. The combination of these factors turns the dienol ether B of Figure 12.23 into a species for which there is no analog in enamine chemistry. 

Figure 12.24 depicts the oxidation of a silyl enol ether A to give an a,/3-unsaturated ketone B. Mechanistically, three reactions must be distinguished. The first justifies why this reaction is introduced here. The silyl enol ether A is electrophilically substituted by palladium(II) chloride. The a-palladated cyclohexanone E is formed via the intermediary O-silylated oxocarbenium ion C and its parent compound D. The enol content of cyclohexanone, which is the origin of the silyl enol ether A, would have been too low to allow for a reaction with palladium(II) chloride. Once more, the synthetic equivalence of a silyl enol ether and a ketonic enol is the basis for success (Figure 12.24). 

Silylated cyanohydrins have also been prepared via silylation of cyanohydrins themselves9 and by the addition of hydrogen cyanide to silyl enol ethers.10 Sllylated cyanohydrins have proved to be quite useful 1n a variety of synthetic transformations, including the regiospecific protection of p-quinones,11 as Intermediates in an efficient synthesis of a-aminomethyl alcohols,6 and for the preparation of ketone cyanohydrins themselves.1 The silylated cyanohydrins of heteroaromatic aldehydes have found extensive use as acyl anion equivalents, providing general syntheses of ketones13 and acyloins.1 ... 

Condensation with ketones. The aminals serve as synthetic equivalent of trifluoroacetaldehyde. Thus, its condensation with ketones (catalyzed by aqueous HCl) gives 2-(l-hydroxy-2,2,2-trifluoroethyl) ketones and reaction with silyl enol ethers I catalyzed by ZnCl ) delivers the trifluoroethylidene ketones. 

A larger number of silyl enol ethers have been studied by kinetic measurements with regard to their synthetic value as dienophiles and their reactivity the readily accessible silyl enol ethers proved to be enol equivalents <92TL8019>. Synthesis of novel heterocyclic clefts such as (153) and (154) can be achieved by (4 -I- 2) cycloaddition reactions of 1,2,4,5-tetrazines (151) with polycyclic diketones... 

While silyl enol ethers 21 and 23 were subjected to similar reaction conditions (Tables 1.5 and 1.6), the allylic C—H bond could also be functionalized by metal carbenoids to afford silyl-protected 1,5-dicarbonyls 22 and 24 respectively, which can be viewed as an equivalent of an asymmetric Michael reaction. Although the double bond is highly electron-rich and readily undergoes cyclopropanation in the presence of most other metal carbenoids, by using aryldiazoacetates 1 as carbene precursors, cyclic silyl enol ethers 21 were readily transformed into their corresponding allylic C—H bond insertion products 22 (22 ) in excellent yields, excellent ee and moderate de (Table 1.5). Noticeably, while acyclic silyl enol ethers 23 were subjected to the reaction, excellent diastereoselectivity (>90% de) was obtained, which shows great potential in synthetic applications (Table 1.6). 

Various oxidations of amines can also generate acyliminium ions. The methods most used in synthetic procedures involve electrochemical oxidation to form a-alkoxy amides and lactams, which then generate acyliminium ions. Acyliminium ions are sufficiently electrophilic to react with enolate equivalents such as silyl enol ethers and enol... 

The tricarbonylcyclohexadienyliumiron salts (32) are synthetically equivalent to substituted phenyl cations/ and react with silyl enol ethers to give, after decomplexation, the a-(cyclohexa-l,3-dienyl) ketones, which are readily oxidized to a-aryl ketones. 2-Substituted cyclopent-2-enones can be prepared from the salts and l,2-bis(trimethyIsilyloxy)cyclopentene (Scheme 52).A... 

The catalytic [2-1-2] cycloaddition reactions are an essential and important tool for the syntheses of cyclobutane derivatives. In particular, the catalytic cycloaddition reactions of silyl enol ethers, which are the most easily prepared ketone equivalents, have been an attractive method for cyclobutane syntheses. A number of catalytic methods that give high stereoselectivities and yields have been developed. Recently, several studies on the synthetic utilization of the [2-1-2] cycloaddition have been reported [43]. Further improvements are required for more practical and large scale syntheses. We look forward to further developments of the [2-1-2] cycloaddition reaction with silyl enol ethers in the near future. 

Silyl(methoxy)benzotriazol-l-ylmethane 62 is lithiated with BuLi to give the corresponding anion, which undergoes Peterson reactions with carbonyl compounds (Scheme 2.40) [100, 101]. The products, l-(l-methoxy-l-alkenyl)benzotriazoles 63, are synthetically equivalent to an acylbenzotriazole synthon in which the carbonyl group is masked as an enol ether [102, 103]. Transformation of the alkenyl ethers into carboxyhc acids is readily achieved by treatment with zinc bromide and hydrochloric add in refluxing 1,4-dioxane [104]. 

As mentioned earlier, metal complexation not only allows isolation of the QM derivatives but can also dramatically modify their reactivity patterns.29o-QMs are important intermediates in numerous synthetic and biological processes, in which the exocyclic carbon exhibits an electrophilic character.30-33 In contrast, a metal-stabilized o-QM can react as a base or nucleophile (Scheme 3.16).29 For instance, protonation of the Ir-T 4-QM complex 24 by one equivalent of HBF4 gave the initial oxo-dienyl complex 25, while in the presence of an excess of acid the dicationic complex 26 was obtained. Reaction of 24 with I2 led to the formation of new oxo-dienyl complex 27, instead of the expected oxidation of the complex and elimination of the free o-QM. Such reactivity of the exocyclic methylene group can be compared with the reactivity of electron-rich enol acetates or enol silyl ethers, which undergo electrophilic iodination.34... 

Vinyl sulfoxides (221), which are aldehyde a-cation equivalents, and vinylthiolium ions (230), which are a.jj-unsaturated carbonyl 3-cation equivalents, are also suitable acceptors for silyl ketene acetals and enol silyl ethers (Scheme 36). Kita reports that the bulky r-butyldimethylsilyl ketene acetals and tri-methylsilyl ketene acetals form 1 1 adducts (224) and 1 2 adducts (225) with (221), respectively 91 mechanistically, these additions proceed via an initial Pummerer rearrangement The vinylthiolium ion additions are notable for their synthetic flexibility for example, additions to the ketene dithioacetal (229) proceed with higher diastereoselectivity than the corresponding enolate additions to a,3-unsaturated esters.9 lc,91d... 

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