Trimethylsilyl enol ethers preparation from ketones

Trimethylsilyl enol ethers prepared in 60-91% yields from ketone enolates and trimethylsilyl chloride are converted into a-hydroxy ketones by chromyl chloride in 62-82% yields (equation 402) [676] (equation 340). 

This procedure illustrates a new three-step reaction sequence for the one-carbon ring expansion of cyclic ketones to the homologous tt,/3-unsaturated ketones. The key step in the sequence is the iron(III) chloride-induced cleavage of the central bond of trimethyl-silyloxycyclopropanes which me obtained by cyclopropanation of trimethylsilyl enol ethers. The procedure for the preparation of 1-trimethylsilyloxycyclohexene from cyclohexanone described in Part A is that of House, Czuba, Gall, and Olmstead. ... 

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 method can be further improved using trimethylsilyl (TMS) enol ethers, which can be prepared in situ from aldehydes and ketones [49]. TMS enol ethers of cyclic ketones are also suitable, and diversity can be enhanced by making either the kinetic or thermodynamic enol ether, as shown for benzyl methyl ketone. Thus, reaction of the kinetic TMS enol ether 10-133 with the amino aldehyde 10-134 and dimethylbarbituric acid 10-135 yielded 10-136, whereas the thermodynamic TMS enol ether 10-137 led to 10-138, again in excellent purity, simply by adding diethyl ether to the reaction mixture (Scheme 10.33). 

Cycloheptane annelation (7, 212). The mixed cuprate 1 reacts with acid chlorides to afford vinylcyclopropyl ketones. Previously these ketones were prepared from aldehydes by condensation with l-lithio-2-vinylcyclopropane followed by oxidation (7, 192-193). These compounds are rearranged to 4-cycloheptenones on conversion to trimethylsilyl enol ethers, thermolysis, and hydrolysis. ... 

Trimethylsilyl enol ethers proved to be unsuitable substrates due to the ease of hydrolysis to the ketone. Presumably, for the same reason, the yield of the a-azido ketone prepared from 17 dropped to less than 50% on reaction scales larger than 100 mg125. 

The TiCLrmediated Mukaiyama aldol reactions between 7r-allyltricarbonyliron lactone complexes and chiral aldehydes were well documented by Ley and coworkers [37]. (/ )-Trimethylsilyl enol ether 23 (>96% ee) was prepared from the methyl ketone complex 22 by treatment with MesSiOTf/EtsN in CH2CI2 and this was then reacted with (R)- and (5)-2-benzyloxypropanal 24 under the influence of TiCl4 in CH2CI2 at -78 °C. Although the reactions proceeded very slowly and apparent hydrolysis of the silyl enol ether occurred, the aldol products 25 and 26 were isolated in excellent diastereoselectivity in both cases (Scheme 1-8). Interest-... 

Regiospecific preparation of a-benzoyloxy carbonyl compounds by lead tetrabenzoate (LTB) oxidation of the trimethylsilyl enol ethers is possible. Similarly, a-thiolated ketones can be prepared from a disulfide. 71... 

Trimethylsilyl enul ethers. House et al. have described two procedures for the preparation of trimethylsilyl enol ethers from aldehydes and ketones. In one method triethylamine in THF is used as base. These conditions usually afford an equilibrium mixture, and in fact the method is very satisfactory for equilibration. The more highly substituted enol ether usually predominates, as in the example ... 

In their paper on the preparation of trimethylsilyl enol ethers, House et al. [1] illustrate the generation of lithium enolates with the reaction between 2-methylcyclohexanone and LDA using 1,2-dimethoxyethane as a solvent. The authors do not indicate a temperature range for the lithiation of the ketone, but we found the deprotonation of a variety of ketones to proceed extremely fast and with excellent results at temperatures in the region of — 70 °C. In view of the possibility of aldol condensation, dropwise addition of the ketone to the LDA solution seems advisable. Attempts to prepare enolates from aldehydes RCH2CH=0 and LDA gave, after quenching with trimethylchlorosilane, only unidentified resinous products. 

TrimethylsUyl enol ethers. It is relatively easy to obtain trimethylsilyl enol ethers formed under kinetic control from unsymmetrical ketones in high yields by use of LDA as ba (3, 310 311). However, the more highly substituted enol ethers formed by thermodynamic control have not been available as readily. A new method that leads to the more highly substituted ether uncontaminated with the less highly substituted ether is reduction of n-halo-a-substituted ketones with activated zinc (I, 1276) in ether TMIiDA followed by addition of chloro-trimcthylsilanc in ether. The starting materials can Ire prepared by ehlorination of the, < dkvl ketf>iie with stdliiryl chloride. ... 

Formation of Trimethylsilyl Enol Ethers from Enolizable Aldehydes and Ketones. The most common methods for preparing silyl enol ethers use silyl chlorides or silyl triflate/base combinations and need careful attention during workup of the reaction and isolation of the enol ether. Silylations with BS A are generally mild and nearly neutral and do not require the addition of a supplementary base. Ionic liquids have been used for the preparation of silyl enol ethers 31 from aldehydes and ketones 30 with BS A in good yields (eq 38). These new reaction conditions open an important alternative to the use of highly toxic HMPA as solvent. ... 

Trimethylsilyl enol ethers can be prepared directly from ketones. One procedure involves reaction with trimethylsilyl chloride and a tertiary amine. This procedure gives the regioisomers in a ratio favoring the thermodynamically stable enol ether. Use of t-butyldimethylsilyl chloride with potassium hydride as the base also seems to favor the thermodynamic product.Trimethylsilyl trifluoromethanesulfonate (TMS triflate), which is more reactive, gives primarily the less substituted trimethylsilyl enol ether (entry 5, Scheme 1.3). The best ratio of less substituted to more substituted enol ether is obtained by treating a mixture of ketone and trimethylsilyl chloride with LDA at Under these conditions, the kinetically preferred... 

The success of this approach to specific enolates is dependent on the availability of the regioisomerically pure silyl enol ethers. The more highly substituted silyl ethers usually predominate in the mixture produced by reaction of the enolates, prepared under equilibrium conditions, with trimethylsilyl chloride (1.20). In some cases this mixture may be purified by distillation or by chromatography. The less highly substituted silyl ethers are obtained from the enolate prepared from the ketone under kinetic conditions with lithium diisopropylamide (LDA). 

Cleavage of enol trimethylsilyl ethers or enol acetates by methyllithium (entries 1 and 2, Scheme 1.3) as a route to specific enolate formation is limited by the availability of these materials. Preparation of the enol trimethylsilyl ethers and enol acetates from the corresponding ketones usually affords a mixture of the two possible derivatives, which must be then separated. It is sometimes possible to find conditions that favor the formation of one isomer for example, reaction of 2-methyl-cyclohexanone with lithium diisopropylamide and trimethylchlorosilane affords the less highly substituted enol ether preferentially by 99 1 over the more highly substituted one (kinetically controlled conditions). ... 

Preparative Method the best procedure for the preparation of trimethylsilylacetone is the reaction of trimethylsilyl-methylmagnesium chloride or bromide with acetic anhydride. Other useful preparative methods for a-trimethylsilyl ketones involve the reaction of trimethylsilylmethylmagnesium chloride with acid chlorides, or with aldehydes followed by oxidation of the resulting /3-hydroxysilane to the ketone. When the trialkylsilyl group is very large, particularly the triisopropylsilyl group, a rearrangement from the silyl enol ether to the a-silyl ketone is possible. ... 

Silyl enol ethers are usually prepared by treating a ketone with trimethylsilyl chloride and triethylamine in refluxing DMF. In unsymmet-rical ketones, this gives the more substituted double bond (Eq. 6.38) [63]. When the less substituted product is desired, it is made from the less... 

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