Trimethylsilyl enol ethers, oxidation

More traditional carbon nucleophiles can also be used for an alkylative ring-opening strategy, as exemplified by the titanium tetrachloride promoted reaction of trimethylsilyl enol ethers (82) with ethylene oxide, a protocol which provides aldol products (84) in moderate to good yields <00TL763>. While typical lithium enolates of esters and ketones do not react directly with epoxides, aluminum ester enolates (e.g., 86) can be used quite effectively. This methodology is the subject of a recent review <00T1149>. 

Palladium-catalyzed bis-silylation of methyl vinyl ketone proceeds in a 1,4-fashion, leading to the formation of a silyl enol ether (Equation (47)).121 1,4-Bis-silylation of a wide variety of enones bearing /3-substituents has become possible by the use of unsymmetrical disilanes, such as 1,1-dichloro-l-phenyltrimethyldisilane and 1,1,1-trichloro-trimethyldisilane (Scheme 28).129 The trimethylsilyl enol ethers obtained by the 1,4-bis-silylation are treated with methyllithium, generating lithium enolates, which in turn are reacted with electrophiles. The a-substituted-/3-silyl ketones, thus obtained, are subjected to Tamao oxidation conditions, leading to the formation of /3-hydroxy ketones. This 1,4-bis-silylation reaction has been extended to the asymmetric synthesis of optically active /3-hydroxy ketones (Scheme 29).130 The key to the success of the asymmetric bis-silylation is to use BINAP as the chiral ligand on palladium. Enantiomeric excesses ranging from 74% to 92% have been attained in the 1,4-bis-silylation. 

F. Trimethylsilyl enol ethers are treated with Simmons-Smith reagent to form cyclopropyl silyl ethers. These rings undergo oxidative cleavage and ring expansion when treated with... 

Other methods for a-hydroxy ketone synthesis are addition of O2 to an enolate followed by reduction of the a-hydroperoxy ketone using triethyl phosphite 9 the molybdenum peroxide-pyridine-HMPA oxidation of enolates 10 photooxygenation of enol ethers followed by triphenylphosphine reduction 11 the epoxidation of trimethyl silyl enol ethers by peracid 1 - the oxidation of trimethylsilyl enol ethers by osmium tetroxide in N-methylmorpholine N-... 

Diketones (8, 126 127). Complete details of the synthesis of 1,4-diketones by oxidative coupling of ketone enolales and trimethylsilyl enol ethers with Cu(OTf)2 are available.1 Use of isobutyronitrile is essential for the coupling it is not only a suitable solvent, but the nitrile group apparently facilitates reduction of the intermediate copper enolate to CuOTf.2 When acetonitrile is used by-products containing a nitrile group are formed. 1,4-Diketones are formed only in traces when DMF, DMSO, or HMPT is used. 

Azlactone oxidation Azlactones derived from dipeptides are more readily dehydrogenated than the dipeptides. This route to dehydropeptides has been examined with several reagents. Halogenation dehydrohalogenation is possible, but yields at best are 50%. Various oxidation procedures are about as effective. The most satisfactory method is oxidation of the corresponding trimethylsilyl enol ether with DDQ. However, this oxidation is limited to aryl azlactones. 

Electron transfer provides a very efficient methodology to the cross-coupling of 1,2-disubstituted and 1-substituted trimethylsilyl enol ethers as demonstrated by Baciocchi and Ruzziconi [208]. Thus, the synthetically important, un-symmetrical 1,4-diketones 107 were formed in good yields from 102 and 104 using Ce(NH. )2(N03)6 (CAN) as one-electron oxidant. 

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. ... 

Epoxide -> aliylic alcohol. Treatment of an oxirane with equimolar amounts of 1 and DBU in an aromatic solvent affords aliylic trimethylsilyl ethers in moderate yield. 2,2-Di-, tri-, and tetrasubstituted oxiranes, as well as oxides of cycloalkenes, react at 23° or below. 2,3-Di- and monosubstituted oxiranes do not react at this temperature these species react with 1 and DBU at 70-80° to give trimethylsilyl enol ethers. The reaction of epoxycyclooctane gives a product of transannular cyclization. In the case of epoxycyclohexane, the intermediate 2 has been isolated. 

Recently, Armstrong and Tsuchiya have prepared the chiral tetrahydropyranone 56 and examined its use in asymmetric epoxidation reactions. Phenylcyclohexene oxide was formed in excellent yield and high ee however, low enantioselectivity was observed with a trimethylsilyl enol ether (Scheme 21) <2006T257>. 

Trimethylsilyl enol ethers treated with chromyl chloride in dichloromethane at -78 °C furnish a-hydroxy ketones in 62-82% yields [676]. The same products are obtained by oxidation with m-chloroperoxybenzoic acid... 

In the laboratory of FI. Flagiwara, the first total synthesis of the polyketide natural product (-)-solanapyrone E was achieved. The installation of the pyrone moiety required the addition of the b/s(trimethylsilyl) enol ether of methyl acetoacetate to a bicyclic aldehyde precursor in the presence of titanium tetrachloride. The resulting -hydroxy- -ketoester was oxidized with the Jones reagent to afford the corresponding -diketoester in good yield. 

Rubottom, G. M., Vazquez, M. A., Pelegrina, D. R. Peracid oxidation of trimethylsilyl enol ethers. Facile a-hydroxylation procedure. Tetrahedron Lett. 1974, 4319-4322. 

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... 

Reductive removal of the halogen was achieved with tributyltin hydride and subsequent ozonolysis gave aldehyde 221. An aldol condensation of 221 with the trimethylsilyl enol ether of methyl propionate, followed by Jones oxidation... 

Oxidation of alkenyllithiums with bis(trimethyisilyi)peroxide gives trimethylsilyl enol ethers, which may be easily hydrolyzed to the corresponding ketones [47]. 

Trimethylsilyl enol ethers can be thermally dimerized to the corresponding silyl-protected tetrafluorocyclobutanediols [33]. If these intermediates are desilylated by use of TBAF the resulting trans diol is stable whereas the cis diol undergoes clean conversion to the 2,2,3,3-tetrafluorobutane-l,4-dione (Scheme 2.199). Ring opening is assumed to proceed via a diradical which is oxidized by ambient air to the diketone. 

The Rubottom oxidation1 is the peracid-mediated oxidation of trimethylsilyl enol ethers to afford a-silyloxy- or a-hydroxy aldehydes or ketones.2,3 Use of an aqueous workup generally affords the hydroxy compounds, whereas nonaqueous workups provide the silyloxy derivatives. For example, the enolsilane 1 derived from cycloheptanone was converted to 2 in 77% yield by treatment with /w-CPBA followed by workup with 10% aqueous sodium hydroxide. Omission of the aqueous workup afforded 3 in 85% isolated yield,1 ... 

The preparation of the methyl ketone required for the aldol coupling reaction was accomplished by using the asymmetric alkylation of the unsaturated amide 158 according to a protocol developed by Myers [112]. Asymmetric alkylation of 158 with ethyl iodide gave 159 which was reduced to the primary alcohol (LiNH2, BH3) and protected as a PMB ether to produce, after oxidative cleavage of the olefin, the methyl ketone 160 which was converted to the trimethylsilyl enol ether 161 (LiHMDS, TMSC1) (Scheme 31). 

In the presence of a Lewis acid, silyl enol ethers can be alkylated with reactive secondary halides, such as substituted benzyl halides, and with chloromethylphenyl sulfide (ClCH2SPh), an activated primary halide. Thus, reaction of the benzyl chloride 10 in the presence of zinc bromide with the trimethylsilyl enol ether derived from mesityl oxide allowed a short and efficient route to the sesquiterpene ( )-ar-turmerone (1.22). Reaction of ClCH2SPh with the trimethylsilyl enol ethers of lactones in the presence of zinc bromide, followed by 5-oxidation and pyrolytic ehmination of the resulting sulfoxide (see Section 2.2), provides a good route to the a-methylene lactone unit common in many cytotoxic sesquiterpenes (1.23). Desulfurization with Raney nickel, instead of oxidation and elimination, affords the a-methyl (or a-alkyl starting with RCH(Cl)SPh) derivatives. ... 

Several possible methods can be used for the conversion of carbonyl compounds to a,(3-unsaturated carbonyl compounds. For aldehydes, such as undecanal, it is normally best to prepare the trimethylsilyl enol ether (using MesSiCl and EtsN in DMF) and then use 10 mol% Pd(OAc)2 in DMSO under an atmosphere of oxygen. See R. C. Larock, T. R. Hightower, G. A. Kraus, P. Hahn and D. Zheng, Tetrahedron Lett., 36 (1995), 2423. Attempts to use LDA (then PhSeBr and oxidative elimination) will result in reduction of the aldehyde. 

Oxidation of trimethylsilyl enol ethers with m-chloroperbenzoic acid is regio-specific, and gives a-hydroxyketones in good yield. 

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