Propiophenone, enol silyl ether

The combination of fluoride ions and enol silyl ethers provides a useful method for the generation of enolate anions [13]. Watts, Haswell, and coworkers applied a borosilicate glass microreactor, with channel dimensions of 100 pm x 50 pm, equipped with an EOF (electro-osmotic flow) pumping system, to the C-acylation of enolate anions, which leads to 1,3-diketones [14,15]. ATHF solution of tetrabu-tylammmonium fluoride (TBAF) was placed in reservoir A, a THF solution of benzoyl fluoride in reservoir B, and enol silyl ether of propiophenone was placed in reservoir C. The desired 1,3-diketone was formed in 100% conversion (Scheme 5.11). As for enol silyl ether of acetophenone, benzoyl cyanide was... 

Using other hypervalent iodine compounds or different reagent combinations, various functional groups can be introduced in the a-position of ketones. a-Tosylations of ketones can be achieved directly using [hydroxy(tosyloxy)-iodo]benzene 6. The major drawback is the low regioselectivity observed in these reactions, although the a-tosylation of silyl enol ethers circumvents this problem. In the last few years some efforts have been done in the synthesis of chiral hypervalent iodine compounds [48, 53-55,113-117], but only a few of them have been used successfully in stereoselective synthesis. With chiral derivatives of type 59 it is possible to a-tosylate propiophenone with about 40% ee [56,118,119]. 

Mukaiyama aldol reactions of various silyl enol ethers or ketene silyl acetals with aldehydes or other electrophiles proceed smoothly in the presence of 2 mol % B(CgF5)3 [151a,c]. The following characteristic features should be noted (i) the products can be isolated as j8-trimethylsilyloxy ketones when crude adducts are worked-up without exposure to acid (ii) this reaction can be conducted in aqueous media, so that the reaction of the silyl enol ether derived from propiophenone with a commercial aqueous solution of formaldehyde does not present any problems (iii) the rate of an aldol reaction is markedly increased by use of an anhydrous solution of B(C6Fs)3 in toluene under an argon atmosphere and (iv) silyl enol ethers can be reacted with chloromethyl methyl ether or trimethylorthoformate hydroxymethyl, methoxy-methyl, or dimethoxymethyl Cl groups can be introduced at the position a to the carbonyl group. These aldol-type reactions do not proceed when triphenylborane is used (Eq. 92). 

Lewis acid catalysis in micellar systems was first found in the model reaction of the silyl enol ether of propiophenone with benzaldehyde. Although the reaction proceeded sluggishly in the presence of 0.2 equiv. Yb(OTf)3 in water, remarkable enhancement of the reactivity was observed when the reaction was carried out in the presence of 0.2 equiv. Yb(OTf)3 in an aqueous solution of sodium dodecylsul-fate (SDS, 0.2 equiv., 35 mM), and the corresponding aldol adduct was obtained in a 50% yield. In the absence of the Lewis acid and in surfactant (water-promoted conditions) [11], only 20% yield of the aldol adduct was isolated after 48 h, while a 33% yield of the aldol adduct was obtained after 48 h in the absence of the Lewis acid in an aqueous solution of SDS. The amounts of the surfactant also influenced the reactivity, and the yield was improved when Sc(OTf)3 was used as a Lewis acid catalyst. Judging from the critical micelle concentration, micelles would be formed in these reactions, and it is noteworthy that the Lewis acid-catalyzed reactions proceeded smoothly in micellar systems [25]. 

In fact, Sc(DS)3 worked very efQciently in the aldol reaction of benzaldehyde with the silyl enol ether derived from propiophenone in water, whereas the reaction proceeded sluggishly when Sc(OTf)3 was the catalyst (Scheme 15.3). ... 

It was found that the hydroxymethylation of silyl enol ethers with commercial formaldehyde solution proceeded smoothly by using lanthanide triflates as Lewis acid catalysts [7,13], The reactions were first carried out in commercial formaldehyde solution-THF media. The amount of the catalyst was examined by taking the reaction of the silyl enol ether derived from propiophenone with commercial formaldehyde solution as a model, and the reaction was found to be catalyzed even by 1 mol% ytterbium triflate (Yb(OTf)3) [Eq. (1)]. 

The effects of lanthanide triflates in the reaction of the silyl enol ether of propiophenone (1) with commercial formaldehyde solution were examined [19]. In most cases, the reactions proceeded smoothly to give the corresponding adducts in high yields (Table 8.1). The reactions were most effectively carried out in commercial formaldehyde solution-THF medium under the influence of a catalytic amount of Yb(OTf)3. 

Lewis-acid catalysis in micellar systems was first found in the model reaction of the silyl enol ether of propiophenone (1) with benzaldehyde (Table 8.23). While the reaction proceeded sluggishly in the presence of 0.2 eq. Yb(OTf)3 in water, remarkable enhancement of the reactivity was observed when the reaction was carried out in the presence of 0.2 eq. 

Lectka and coworkers took advantage of the high electrophilic reactivity of the carbon-nitrogen double bond in the AT-tosyl imino ester 340 and studied enantioselective additions of ketone-derived silyl enol ethers 220, mediated by (7 )-To1-BINAP-CuC104 (341). The loading of ligand and metal salt could be reducedto 2 mol%. Keto esters 342 were thus obtained in high chemical yields and enantiomeric excess, which could be increased to 99% ee after recrystallization (Scheme 5.92) [175]. The protocol was extended to propiophenone-derived... 

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