Aldehydes enol silyl ethers

Acylsilanes are versatile intermediates for carbon-carbon bond formation reactions, and may serve as precursors for the synthesis of silyl enol ethers, aldehydes, or carboxylic acids. In the presence of a base or certain nucleophiles, they undergo the Brook rearrangement, where the silyl moiety migrates from carbon to oxygen (see below in this section). 

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]... 

Silylated cyanohydrins have also been prepared via silylation of cyanohydrins themselves and by the addition of hydrogen cyanide to silyl enol ethers. Silylated cyanohydrins have proved to be quite useful in a variety of synthetic transformations, including the regiospecific protection of p-quinones, as intermediates in an efficient synthesis of a-aminomethyl alcohols, and for the preparation of ketone cyanohydrins themselves.The silylated cyanohydrins of heteroaromatic aldehydes have found extensive use as... 

The in situ cyanosilylation of p-an1saldehyde is only one example of the reaction which can be applied to aldehydes and ketones in general. - The simplicity of this one-pot procedure coupled with the use of inexpensive reagents are important advantages over previous methods. The silylated cyanohydrins shown in the Table were prepared under conditions similar to those described here. Enolizable ketones and aldehydes have a tendency to produce silyl enol ethers as by-products in addition to the desired cyanohydrins. The... 

Selective fluonnation in polar solvents has proved commercially successful in the synthesis of 5 fluorouracil and its pyrimidine relatives, an extensive subject that will be discussed in another section Selective fluonnation of enolates [47], enols [48], and silyl enol ethers [49] resulted in preparation of a/phn-fluoro ketones, fieto-diketones, heta-ketoesters, and aldehydes The reactions of fluorine with these functionalities is most probably an addition to the ene followed by elimination of fluonde ion or hydrogen fluoride rather than a simple substitution In a similar vein, selective fluonnation of pyridmes to give 2-fluoropyridines was shown to proceed through pyridine difluondes [50]... 

The final example concerns cyclization of a silyl enol ether, connected to yet another carbon atom. The (.Ej-enol ether 23 appears to be converted with high stereoselectivity into the aldehyde 24 in 70- 90% yield, while the (Z)-enol ether 23 affords the epimeric aldehyde 25 in similar yield and selectivity164. 

Enolizable compounds can be used for Meerwein reactions provided that the keto-enol equilibrium is not too far on the side of the ketone for example, P-dicar-bonyl compounds such as acetylacetone are suitable (Citterio and Ferrario, 1983). The arylation of enol esters or ethers (10.12) affords a convenient route for arylating aldehydes and ketones at the a-carbon atom (Scheme 10-48). Silyl enol ethers [10.12, R = Si(CH3)3] can be used instead of enol ethers (Sakakura et al., 1985). The reaction is carried out in pyridine. 

The most frequently encountered, and most useful, cycloaddition reactions of silyl enol ethers are Diels-Alder reactions involving silyloxybutadicncs (Chapter 18). Danishefsky (30) has reviewed his pioneering work in this area, and has extended his studies to include heterodienophiles, particularly aldehydes. Lewis acid catalysis is required in such cases, and substantial asymmetric induction can be achieved using either a chiral lanthanide catalyst or an a-chiral aldehyde. 

Silyl enol ethers and ketene acetals derived from ketones, aldehydes, esters and lactones are converted into the corresponding o/i-unsaturated derivatives on treatment with allyl carbonates in high yields in the catalytic presence of the palladium-bis(diphenylphosphino)ethane complex (32). A phosphinc-free catalyst gives higher selectivity in certain cases, such as those involving ketene acetals. Nitrile solvents, such as acetonitrile, are essential for success. 

A mixture of lead(iv) acetate (20 mmol) and KOAc (100 mmol) in AcOH (30 ml) was treated with the neat aldehyde-derived silyl enol ether (20mmol) at ambient temperature. After being stirred for 1 h at ambient temperature, the reaction mixture was diluted with water (30ml), and then extracted with pentane (3 x200ml). The combined pentane extracts were washed with saturated sodium hydrogen carbonate solution (2x50ml), dried, concentrated and distilled to give the product a-acetoxyaldehyde (45-78%). 

Diazonium salts react with oximes to give aryl oximes, which are easily hydrolyzed to aldehydes (R = H) or ketones." A copper sulfate-sodium sulfite catalyst is essential. In most cases higher yields (40-60%) are obtained when the reaction is used for aldehydes than for ketones. In another method for achieving the conversion ArNj —> ArCOR, diazonium salts are treated with R4Sn and CO with palladium acetate as catalyst. In a different kind of reaction, silyl enol ethers of aryl ketones, Ar C(OSiMe3)=CHR, react with sohd diazonium fluoroborates, ArNj BF4, to give ketones, ArCHRCOAr. " This is, in effect, an arylation of the aryl ketone. 

In 1991, Kobayashi el al. prepared novel chiral S/N ligands for the tin-mediated aldol reaction of silyl enol ethers with aldehydes. As an example, the reaction of benzaldehyde afforded the expected syn aldol product as the major product with a good yield and an enantioselectivity of up to 92% ee (Scheme 10.26). Moreover, other aldehydes such as substituted benzaldehydes or aliphatic unsaturated aldehydes were converted into their corresponding aldol products with enantioselectivities of more than 90% ee. It was checked that the corresponding diamine ligands provided less active complexes for the same reactions. 

The preference for chairlike TSs has been confirmed by using deuterium-labeled enolates prepared from the corresponding silyl enol ethers. The ratio of the location of the deuterium corresponds closely to the ratio of the stereoisomeric enolates for several aldehydes.4... 

The Mukaiyama aldol reaction refers to Lewis acid-catalyzed aldol addition reactions of silyl enol ethers, silyl ketene acetals, and similar enolate equivalents,48 Silyl enol ethers are not sufficiently nucleophilic to react directly with aldehydes or ketones. However, Lewis acids cause reaction to occur by coordination at the carbonyl oxygen, activating the carbonyl group to nucleophilic attack. 

Lewis acids such as TiCl4 and SnCl4 induce addition of both silyl enol ethers and ketene silyl acetals to aldehydes.49... 

If there is no other interaction, the reaction proceeds through an acyclic TS and steric factors determine the amount of syn versus anti addition. This is the case with BF3, where the tetracoordinate boron-aldehyde adduct does not offer any free coordination sites for formation of a cyclic TS. Stereoselectivity increases with the steric bulk of the silyl enol ether substituent R1.50... 

In each instance, the silyl enol ether approaches anti to the methyl substituent on the chelate. This results in a 3,4-syn relationship between the hydroxy and alkoxy groups for a-alkoxy aldehydes and a 3,5-anti relationship for (3-alkoxy aldehydes with the main chain in the extended conformation. 

When there is also a stereogenic center in the silyl enol ether, it can enhance or detract from the underlying stereochemical preferences. The two reactions shown below possess reinforcing structures with regard to the aldehyde a-methyl and the enolate TBDMSO groups and lead to high stereoselectivity. The stereochemistry of the (3-TBDMSO group in the aldehyde has little effect on the stereoselectivity. 

Sc(OTf)3 is an effective catalyst in aldol reactions of silyl enol ethers with aldehydes.49 Compared with other typical rare-earth-metal (Y, Yb) trifiates, Sc(OTf)3 has the strongest activity in the reaction of 1-trimethylsiloxycyclohexane with benzaldehyde in dichloromethane. Although the reaction scarcely proceeded at —78°C in the presence of Y(OTf)3 or Yb(OTf)3, the aldol adduct was obtained in 81% yield in the presence of Sc(OTf)3 (Scheme 9). 

In aldol reactions, especially Mukaiyama aldol reactions, TiIV compounds are widely employed as efficient promoters. The reactions of aldehydes or ketones with reactive enolates, such as silyl enol ethers derived from ketones, proceed smoothly to afford /3-hydroxycarbonyl compounds in the presence of a stoichiometric amount of TiCl4 (Scheme 17).6, 66 Many examples have been reported in addition to silyl enol ethers derived from ketones, ketene silyl acetals derived from ester derivatives and vinyl ethers can also serve as enolate components.67-69... 

Mukaiyama aldol reactions of aldehydes with silyl enol ethers are amongst the most widely used Lewis-acid-mediated or -catalyzed reactions. However, trimethylsilyl triflate is not active enough to promote these reactions,66 and more active silicon-based Lewis acids have been developed. One example is the species generated by mixing trimethylsilyl triflate (or chloride) and B(OTf)3,319,320 for which the formulation R3Si + [B(OTf)4] is suggested by NMR experiments. Only a catalytic amount of this was needed to complete Mukaiyama aldol reactions of... 

Sn(OTf)2 can function as a catalyst for aldol reactions, allylations, and cyanations asymmetric versions of these reactions have also been reported. Diastereoselective and enantioselective aldol reactions of aldehydes with silyl enol ethers using Sn(OTf)2 and a chiral amine have been reported (Scheme SO) 338 33 5 A proposed active complex is shown in the scheme. Catalytic asymmetric aldol reactions using Sn(OTf)2, a chiral diamine, and tin(II) oxide have been developed.340 Tin(II) oxide is assumed to prevent achiral reaction pathway by weakening the Lewis acidity of Me3SiOTf, which is formed during the reaction. 

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