Acetoacetates enol silyl ethers

The N,N-bis(formylamido)acetal of cinnamaldehyde 687 condenses with the enol silyl ether of ethyl acetoacetate 724 a, in the presence of TiCl4, to give 79%... 

Normal yS-dicarbonyl compounds such as ethyl acetoacetate 723 a or acetylace-tone 723 b are converted, as the free yS-dicarbonyl compounds or as their sodium salts, by TCS 14, 14/pyridine, or HMDS 2/TCS 14 into their enol silyl ethers 724a [216, 217, 219] and 724b [218]. Yet treatment of / -triketones such as 2-acetyl-dimedone 725 with HMDS 2 results, via the corresponding 2-enol trimethylsilyl... 

Mixed enol silyl ethers and silyl ketene acetals can be derived from keto esters. Methyl acetoacetate is first converted to a monoenol silyl ether (62), which is further silylated by LDA/TMS-CI to the dienol silyl ether (63 Scheme 24). ... 

Transsilylation. Several reagents have been recommended for preparation of /-butyldimethylsilyl ethers by transsilylation. These include allyl-r-butyldimethyl-silane and /-butyldimethylsilyl enol ethers of pentane-2,4-dione and methyl aceto-ucelate,2 both prepared with r-butyldimethylchlorosilane and imidazole. Unlike the reaction of r-butyldimethylchlorosilane with alcohols, which requires a base catalyst, these new reagents convert alcohols to silyl ethers under slightly acidic conditions (TsOH) in good yield. The trimethylsilyl ethers of pentane-2,4-dione and methyl acetoacetate convert alcohols to trimethylsilyl ethers at room temperature even with no catalyst. The former reagent is also useful for silylation of nucleotides.3... 

Among common carbon-carbon bond formation reactions involving carbanionic species, the nucleophilic substitution of alkyl halides with active methylene compounds in the presence of a base, e. g., malonic and acetoacetic ester syntheses, is one of the most well documented important methods in organic synthesis. Ketone enolates and protected ones such as vinyl silyl ethers are also versatile nucleophiles for the reaction with various electrophiles including alkyl halides. On the other hand, for the reaction of aryl halides with such nucleophiles to proceed, photostimulation or addition of transition metal catalysts or promoters is usually required, unless the halides are activated by strong electron-withdrawing substituents [7]. Of the metal species, palladium has proved to be especially useful, while copper may also be used in some reactions [81. Thus, aryl halides can react with a variety of substrates having acidic C-H bonds under palladium catalysis. 

However, such a marked ligand effect of the ester moiety was not observed in the case of methyl acetoacetate (23.5% e.e.)153 or ethyl benzoylacetate (62.3-68.4% e.e.)207. This may be due to the fact that the silyl ether could be produced not only by the hydrosilylation, but also by in situ transfer hydrogenation of the silyl enol ether (a mixture of E and Z isomers), which is formed in the first step of the reaction by dehydrogenative coupling of the enol with the hydrosilane. 

This valuable method utilizes the O-TMS enol ethers derived from either pentane-2,4-dione or methyl acetoacetate, the former being the more reactive. Even t-alcohols are rapidly and quantitatively silylated in DMF at room temperature. A similar technique can be used to introduce the TBDMS group, although here ptsa catalysis is required (4). 

Among other methods for the preparation of alkylated ketones are (1) Alkylation of silyl enol ethers using various reagents as noted above, (2) the Stork enamine reaction (10-69), (3) the acetoacetic ester synthesis (10-67), (4) alkylation of p-keto sul-fones or sulfoxides (10-67), (5) acylation of CH3SOCH2 followed by reductive cleavage (16-86), (6) treatment of a-halo ketones with lithium dialkylcopper reagents (10-57), and (7) treatment of a-halo ketones with trialkylboranes (10-73). 

We referred above to a synthesis of bryostatin that contained a reduction controlled by a 1,3-relationship. Evans synthesis34 contains a 1,3-selective aldol as well as a 1,3-controlled reduction The aldehyde 202, made by an asymmetric aldol reaction, was combined with the double silyl enol ether of methyl acetoacetate to give, as expected, the anti-aldol 203. However, the only Lewis acid that gave this good result was (<-PrO)2TiCl2 and not BF3 thus emphasising the rather empirical aspect of this type of control. Evans s own 1,3-controlled reduction gave the anti,anti-triol 204 that was incorporated into bryostatin. 

The catalytic version of this type of reaction was realized by using acetoacetate derived O-silyl dienolate as nucleophiles in the presence of Carreira s catalyst, giving acetoacetate y-adducts in high yields and enantiomeric excesses [119] (Scheme 14.42). The products are ubiquitous structural subunits in biologically active natural products such as the polyene macrolide antibiotic and medicinally important HMG-CoA reductase inhibitors. This aldol addition can also be catalyzed by BINOL-Ti complex in the presence of 4A MS with moderate to good enantioselectivity [120]. The same catalyst system was also efficient in the asymmetric aldol reaction between the aldehydes and Chan s diene [ 1,3-bis-(trimethylsilyloxy)-l-methoxy-buta-1,3-diene] and other related silyl enol ethers [121, 122] (Scheme 14.43) or the functionalized silyl enol ether such as 2-(trimethylsilyloxy)furan with good to excellent enantioselectivities [123]. 

Full details have appeared of application of the C-silylated ester Me3 iCH2C02Et to silylations of alcohols mediated by fluoride ion (cf. 1,170)." In an extension of earlier work with the TMS enol ethers of esters (4,154), ketene methyl TBDMS acetal (50) has been advocated as a stable readily available reagent for conversion of alcohols to TBDMS ethers under mild conditions." In a related approach the O-silylated derivatives (51) and (52), readily formed from acetylacetone (R = Me) or methyl acetoacetate (R = OMe), have been found to be effective reagents for the transformation of alcohols to their TBDMSand TMS ethers," respectively reagents (51) require acid catalysis whereas (52) react without catalyst. Some further details have appeared... 

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