Ketones, 3-trimethylsilyloxy preparation

An outstandingly reactive diene is l-methoxy-3-(trimethylsilyloxy)-l,3-butadiene ( Danishefsky s diene ) 4, prepared by the action of trimethylsilyl chloride on the ketone 3 in the presence of zinc chloride/triethylamine (equation 7)6. The reaction of diethyl mesoxalate with Danishefsky s diene gives the dihydropyran 5 with the (trimethylsily-loxy)dienes 6 and 7, mixtures of dihydropyrans are obtained, in which the meta-isomers predominate (equations 8 and 9)7. 

Trimethylsilyloxy-substituted alkenes are by far the most widely used enol ethers because of their straightforward preparation from the corresponding ketones (equation 20)78-82 -pjjg electron-rich character of silyl enol ethers allows for highly chemoselective cyclopropanations in the presence of additional double bonds (eqnation 21). ... 

Butadienes substituted with alkoxy groups in the 2-position, e.g., 2-ethoxy-1,3-butadiene,6 have been prepared from methyl vinyl ketone, but they required several conversions and a tedious spinning-band distillation to purify the product. This slight modification of the House procedure has been used to conveniently prepare 2-trimethylsilyloxy-l,3-butadiene from the readily available methyl vinyl ketone. This one-step procedure has provided large amounts of a new and reactive diene for Diels-Alder reactions, as illustrated in Table I. 

It should be noted that several procedures are available for the preparation of l-(trimethylsilyloxy)cyclohexene. In an original report252 it was prepared by heating a dimethylformamide solution of cyclohexanone under reflux with chlorotrimethylsilane in the presence of triethylamine. This procedure is generally satisfactory for aldehydes and symmetrical ketones, or ketones which can enolise in one direction only. The method described in Expt 5.214 employs lithium sulphide as an additive to increase the silylating power of the chlorotrimethylsilane, so that the reaction proceeds at room temperature acetonitrile is used as the solvent.253... 

E,Z)-1 -MetlK)xy-2-methyT3-trimethylsilyloxy-1,3-pentadiene (1). The diene is prepared by silylation of the corresponding ketone with ClSi(CH3)3 using N(CH3)3-ZnCl2. ... 

A related approach exploited a A-cyanomethyl group to serve in the dual role of a nitrogen protecting group and a latent precursor of the formaldehyde im-inium ion (e.g., 478), and this innovative modification in tactics resulted in a simplified route to the c/.v-3a-aryloctahydroindole 474 (203a,c). To this end, the amino ketone 482 was readily prepared in one step by the reaction of 1,2-bis(trimethylsilyloxy)cyclopentene with A -benzyl-A -cyanomethyl amine. When 482 was exposed to [l-(3,4-methylenedioxyphenyl)ethenyl]lithium, a mixture (1 14) of 483 and 484 was obtained. It is noteworthy that the stereochemical sense... 

Hydroxyketones are versatile intermediates in the synthesis of pharmaceutical intermediates and heterocyclic molecules. a-Aryl hydroxyketones have been prepared by reaction of aryl aldehydes with 1,4-dioxane followed by reduction with lithium aluminum hydride (LAH) and by the selective LAH reduction of a-silyloxy a,P-unsaturated esters." WissneC has shown that treatment of acid chlorides with tris(trimethylsilyloxy)ethylene affords alkyl and aryl hydroxymethyl ketones. 1-Hydroxy-3-phenyl-2-propanone (3) has been generated by the osmium-catalyzed oxidation of phenylpropene and by the palladium-catalyzed rearrangement of phenyl epoxy alcohoP both in 62% yield. 

A new procedure for the preparation of P-trimethylsilyloxy ketones and esters from silyl enolates (128) and silyl ketene acetals (128a R = O ) has been developed by Yamamoto et al. (Scheme 54). Good to excellent yields of protected aldol products are obtained using a catalytic amount (O.OS-0.1 equiv.) of dimethylaluminum chloride. However, only a small degree of diastereoselectivity is obtained even when silyl enolates of high stereochemical purity are used. 

Bis(methylthio)pyrimidines 40 have been obtained upon reaction of ketones with triflic anhydride (94MIS59]. Cycloaddition reactions of l,3-diaza-l,3-butadienes with haloketenes have been employed for the synthesis of pyrimidones [94T(50)7579). Reaction of 2-trimethylsilyloxy- and 2-trimethyI-silylthio-l,3-diazabutadienes (41) with enamines derived from aliphatic aldehydes (42) leads regio- and stereoselectiveiy to tetrahydropyri-midin-2(l -ones and thiones (43). This reaction type was also used for preparing quinazolines [94H(37)1109],... 

Diels-Alder Reactions. Although commercially available, 2-trimethylsilyloxy-1,3-butadiene (1) can be easily prepared by sily-lation of methyl vinyl ketone. It has been often used as a reactive diene in Diels-Alder reactions. In nearly all cases with a strongly activated dienophile, the trimethylsilyloxy group ends up 1,4 to the activating group in the adduct. Several representative examples are shown in Table 1. The initial Diels-Alder adduct is a... 

In the presence of a strong base such as LDA, the a-carbon of acetic acid esters can react with the carbonyl group of aldehydes or ketones to give j8-hydroxy esters, which may or may not be dehydrated to a,j8-unsaturated esters. This type of reaction has been exploited for the preparation of racemic [2- C]mevalonolactone (64) (Figure 6.25) and the benzofuran[l- C]acetamide PD 126,212 (67)". In the first case a-deprotonated trimethyl-silyl [2- C]acetate was treated with l-trimethylsilyloxy-3-butanone. Acidic work-up resulted in hydrolytic cleavage of the TMS groups and formation of the lactone system... 

---