Silyl enol ether, selective enolate formation

Fluoroalkyl ketones may be employed as the electrophilic partners in condensation reactions with other carbonyl compounds. The highly electrophilic hexafluoroacetone has been used in selective hexafluoroisopropylidenation reactions with silyl enol ethers and silyl dienol ethers, e.g. formation of 1. ... 

Excellent /(-methyl selectivity is observed in the zinc chloride mediated condensation with 0-silyl enol ethers of 2-pyridinylmethyl thiopropionates109. Supposedly, chelate formation of zinc(II) with the sulfur and the nitrogen atom of the pyridinylmethyl thioester is essential for the high /(-selectivity. The geometry of the ketene acetal also seems to have some influence. 

The composition of the enol ethers trimethylsilyl prepared from an enolate mixture reflects the enolate composition. If the enolate formation can be done with high regio-selection, the corresponding trimethylsilyl enol ether can be obtained in high purity. If not, the silyl enol ether mixture must be separated. Trimethylsilyl enol ethers can be prepared directly from ketones. One procedure involves reaction with trimethylsilyl... 

The use of /i-ketocstcrs and malonic ester enolates has largely been supplanted by the development of the newer procedures based on selective enolate formation that permit direct alkylation of ketone and ester enolates and avoid the hydrolysis and decarboxylation of ketoesters intermediates. Most enolate alkylations are carried out by deprotonating the ketone under conditions that are appropriate for kinetic or thermodynamic control. Enolates can also be prepared from silyl enol ethers and by reduction of enones (see Section 1.3). Alkylation also can be carried out using silyl enol ethers by reaction with fluoride ion.31 Tetraalkylammonium fluoride salts in anhydrous solvents are normally the... 

For the application of trialkylamine/TMSOTf as a selective method for the formation of kinetic silyl enol ethers of some a-aminocarbonyl cyclohexanones see L. Rossi and A. Pecunioso, Tetrahedron Lett.,... 

The key element of this protocol is the initial addition of cationic electrophiles such as rerr-alkyl or acyl cations to the double bond of a DCHC complex of the conjugated enyne 118, which results in the formation of the substituted propargylic cation intermediate 119, Subsequent reaction with pre-selected external nucleophiles, for example allylsilanes or silyl enol ethers, leads to the formation of the final adducts 120. The reaction is carried out as a one-pot, three-component coupling and can be used for the creation of two novel C-C bonds. It is a process somewhat complementary to the stepwise Michael addition described earlier (Scheme 2.31), with a reverse order of E and Nu addition. Oxidative decomplexation of 120 yields the product 121. The overall... 

Since the Lewis acid-promoted reactions of the oxidized products with nucleophiles give the corresponding N-acyl-a-substituted amines efficiently, the present reactions provide a versatile method for selective C-H activation and C-C bond formation at the a-position of amides [138]. Typically, TiCl4-promoted reaction of a-t-butyldioxypyrrolidine 66, which can be obtained by the ruthenium-catalyzed oxidation of l-(methoxycarbonyl)pyrrolidine with f-BuOOH, with a silyl enol ether gave keto amide 67 (81%), while the similar reaction with less reactive 1,3-diene gave a-substituted amide 68 (Eq. 3.80). 

The directed aldol reaction is an important means of selective carbon-carbon bond formation. This reaction is efficiently achieved by the transformation of one carbonyl group to a silylated enol derivative, which subsequently couples with another carbonyl compound with the aid of a Lewis acid, typically TiCl4, as formulated in Eq. (2). This type of directed aldol reaction is called the Mukaiyama aldol reaction, a standard and practical synthetic protocol with broad application which has, accordingly, been reviewed extensively [38-42] in addition to the reviews cited in the introductory section. The fundamental reactions between enol silyl ethers and an aldehyde or a ketone... 

Kobayashi et al. also reported interesting chemoselectivity of aldehydes and imines in the Yb(OTf)3-catalyzed addition reactions of silyl enol ether, allylstannane or trimethylsilyl cyanide [12]. In the competitive reactions between aldehydes and imines, the imines reacted faster than the aldehydes (Tables 4-6). This tendency is not unique to Yb as catalyst selectivity is similar for other Ln(OTf)3. Nuclear magnetic resonance (NMR) studies revealed selective formation of an imine-Yb(OTf)3 complex in the presence of an aldehyde. This preference was reversed when conventional Lewis acids (SnCE, TiCU, TMSOTf, and BF3 OEt2) were used. 

The nucleophilicity of silyl enol ethers has been examined. Base-induced formation of the enolate anion generally leads to a mixture of (E)- and (Z)-isomers, and dialkyl amide bases are used in most cases. The (EjZ ) stereoselectivity depends on the structure of the lithium dialkylamide base, with the highest EjZ) ratios obtained with LiTMP-butyllithium mixed aggregates in THF. ° The use of LiHMDS resulted in a reversal of the (E/Z) selectivity. In general, metallic (Z) enolates give the syn (or erythro) pair, and this reaction is highly useful for the diastereoselective synthesis of these products. 

Reddy, D. R., Thornton, E. R. A very mild, catalytic and versatile procedure for a-oxidation of ketone silyl enol ethers using (salen)manganese(lll) complexes a new, chiral complex giving asymmetric induction. A possible model for selective biochemical oxidative reactions through enol formation. J. Chem. Soc., Chem. Commun. 1992, 172-173. 

While selective reaction of aldehydes takes place with the typical Lewis acids TiCL, SnCl4, TMSOTf, etc., lanthanide triflates [Ln(OTf)3] are unique Lewis acids that change the reaction course dramatically aldimine reacts selectively in the coexistence of aldehydes [70]. Among a series of Ln(OTf)3 tested, Yb(OTf)3 exhibited the most prominent chemoselectivity in addition to high chemical yields. The silyl enol ethers of ketones, allyltributylstannane and Me3SiCN are all applicable as chemoselective nucleophiles (Table 2-9). Preferential formation of Yb(OTf)3-aldimine complexes was postulated by C NMR spectral analysis in the presence of PhCHO and Y-benzylideneaniline. 

Mg bisamides can also be used as strong and selective bases in the formation of synthetically useful enolates. Less higlily substituted silyl enol ethers are regiospecifically prepared in high yield, at approximately room temperature under kinetic conditions, from unsymmetrical cyclic ketones and magnesium bis(diiso-propylamide)[(DA)2Mg] in THF/heptane (Scheme 3.36) [27]. 

Introduction and stereochemical control syn,anti and E,Z Relationship between enolate geometry and aldol stereochemistry The Zimmerman-Traxler transition state Anti-selective aldols of lithium enolates of hindered aryl esters Syn-selective aldols of boron enolates of PhS-esters Stereochemistry of aldols from enols and enolates of ketones Silyl enol ethers and the open transition state Syn selective aldols with zirconium enolates The synthesis of enones E,Z selectivity in enone formation from aldols Recent developments in stereoselective aldol reactions Stereoselectivity outside the Aldol Relationship A Synthesis ofJuvabione A Note on Stereochemical Nomenclature... 

Enol ester formation from crotonaldehyde gives the expected / -selectivity 66. Now the silyl enol ether is formed from this ester, also with the expected double bond geometry. The product 67 has three alkenes each is conjugated with at least one oxygen atom. 

A TMSOTf-initiated cyclization of the dicarbonyl substrate was invoked to explain the reactivity pattern [79]. Selective complexation of the less hindered carbonyl group activates it toward intramolecular nucleophilic attack by the more hindered carbonyl which leads to an oxocarbenium species. Subsequent attack by the enol ether results in addition to the more hindered carbonyl group. The formation of this cyclic intermediate also explains the high stereochemical induction by existing asymmetric centers in the substrates, as demonstrated by Eq. 52, where the stereochemistry at four centers is controlled. A similar reactivity pattern was observed for the bis-silyl enol ethers of / -diketones. The method is also efficient for the synthesis of oxabicyclo[3.3.1] substrates via 1.5-dicarbonyl compounds, as shown in Eq. 53. Rapid entry into more complex polycyclic annulation products is possible starting from cyclic dicarbonyl electrophiles [80]. 

The alkoxyalkylation reaction of carbonyl compounds can be considered as an orientated cross-aldol condensation between two masked carbonyl compounds, an acetal and a silyl enol ether. The key step involves the formation of an electrophilic species by reaction of the acetal with catalytic amounts of a Lewis acid and the right catalyst can lead to excellent diastereo- and enantio-selectivities. Clays are satisfactory catalysts in these reactions, with the acid-treated clay K10 performing better than the more powerfully acidic clay KSF,... 

Enoxysilacyclobutanes. These compounds can be prepared by Wurtz coupling of 3-chloropropyltrichlorosiIane with Mg in ether. Introduction of one alkyl group is accomplished by reaction with an organolithium reagent, and the silyl chloride can then be used for the formation of silyl enol ethers. Such 0-silyl ketene acetals are extremely reactive in aldol condensations with aldehydes without catalysts. The reaction is syn-selective. An asymmetric version uses silyl ketene acetals bearing a chiral Si-alkoxy (e.g., 8-phenylmenthoxy) group instead of an alkyl substituent. 

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