Enol ethers, silyl diketones

A TMSOTf-initiated cyclization of the dicarbonyl substrate was invoked to explain the reactivity pattern [79]. Selective complexation of the less hindered carbonyl group activates it toward intramolecular nucleophilic attack by the more hindered carbonyl which leads to an oxocarbenium species. Subsequent attack by the enol ether results in addition to the more hindered carbonyl group. The formation of this cyclic intermediate also explains the high stereochemical induction by existing asymmetric centers in the substrates, as demonstrated by Eq. 52, where the stereochemistry at four centers is controlled. A similar reactivity pattern was observed for the bis-silyl enol ethers of / -diketones. The method is also efficient for the synthesis of oxabicyclo[3.3.1] substrates via 1.5-dicarbonyl compounds, as shown in Eq. 53. Rapid entry into more complex polycyclic annulation products is possible starting from cyclic dicarbonyl electrophiles [80]. 

Potassium enolates derived from acylfulvalenes were trapped with TBDMSCl but not TMSCl or diphenylmethylsilyl chloride. Interestingly, TBDMSCl was found to be compatible with CpK anion at —78 °C. TBDMS enol ethers have also been used as /3-acyl anion equivalents. The TBDMS-silyl enol ethers of diketones (eq 7) and /3-keto esters (eq 8) may be prepared by mixing them with TBDMSCl in THF with imidazole. Alcohols may be protected under acidic conditions as their TBDMS ethers by treatment with /3-silyl enol ethers in polar sovents. 

Selective fluonnation in polar solvents has proved commercially successful in the synthesis of 5 fluorouracil and its pyrimidine relatives, an extensive subject that will be discussed in another section Selective fluonnation of enolates [47], enols [48], and silyl enol ethers [49] resulted in preparation of a/phn-fluoro ketones, fieto-diketones, heta-ketoesters, and aldehydes The reactions of fluorine with these functionalities is most probably an addition to the ene followed by elimination of fluonde ion or hydrogen fluoride rather than a simple substitution In a similar vein, selective fluonnation of pyridmes to give 2-fluoropyridines was shown to proceed through pyridine difluondes [50]... 

Addition of alkyllithium to cyclobutanones and transmetallation with VO(OEt)Cl2 is considered to give a similar alkoxide intermediates, which are converted to either the y-chloroketones 239 or the olefinic ketone 240 depending on the substituent of cyclobutanones. Deprotonation of the cationic species, formed by further oxidation of the radical intermediate, leads to 240. The oxovanadium compound also induces tandem nucleophilic addition of silyl enol ethers and oxidative ring-opening transformation to produce 6-chloro-l,3-diketones and 2-tetrahydrofurylidene ketones. (Scheme 95)... 

Schafer reported that the electrochemical oxidation of silyl enol ethers results in the homo-coupling products. 1,4-diketones (Scheme 25) [59], A mechanism involving the dimerization of initially formed cation radical species seems to be reasonable. Another possible mechanism involves the decomposition of the cation radical by Si-O bond cleavage to give the radical species which dimerizes to form the 1,4-diketone. In the case of the anodic oxidation of allylsilanes and benzylsilanes, the radical intermediate is immediately oxidized to give the cationic species, because oxidation potentials of allyl radicals and benzyl radicals are relatively low. But in the case of a-oxoalkyl radicals, the oxidation to the cationic species seems to be retarded. Presumably, the oxidation potential of such radicals becomes more positive because of the electron-withdrawing effect of the carbonyl group. Therefore, the dimerization seems to take place preferentially. 

Silyl enol ethers can be dimerized to symmetrical 1,4-diketones by treatment with Ag20 in dimethyl sulfoxide or certain other polar aprotic solvents.465 The reaction has been performed with R2, R-1 = hydrogen or alkyl, though best yields are obtained when R2 = R1 = H. In certain cases, unsymmetrical 1,4-diketones have been prepared by using a mixture of two silyl enol ethers. Other reagents that have been used to achieve either symmetrical or cross-coupled products are iodosobenzene-BFy-EtiO.466 ceric ammonium nitrate,467 and lead tetraacetate.m If R1 = OR (in which case the substrate is a ketene silyl acetal), dimerization with TiCL, leads to a dialkyl succinate (32, R1 = OR).4 9... 

Michael reaction. In the presence of (C6H5)3CC104, silyl enol ethers undergo Michael addition to a,p-enones. The adducts can be isolated or rearranged to 1,5-diketones by base. The intermediates cannot be isolated from reactions catalyzed by TiCl4 or CsF. 

Since silyl enol ethers have a silyl group ji to the jr-system, anodic oxidation of silyl enol ethers takes place easily. In fact, anodic oxidation of silyl enol ethers proceeds smoothly to provide the homo-coupling products, 1,4-diketones (equations 37 and 38)42. This dimerization of the initially generated cation radical intermediate is more likely than the reaction of acyl cations formed by two electron oxidation of unreacted silyl enol ethers in these anodic reactions. 

Diketones. Silyl enol ethers are C-acylated by acetyl tetrafluoroborate to give 1,3-diketones. Yields are generally higher if the reagent is generated in situ from CH3COF and BF3.2 Examples ... 

Just recently, a cyclo-cyanosilylation has been described321. Ryu and his coworkers have taken dicyanodimethylsilane (J>43)310) as a reagent under the conditions of the common cyanosilylation and obtained cyclic silyl enol ether (544,545) when (S-hydroxyketones or j8-diketones were employed (Scheme 87). 

Diketones and a-(chlorocarbonyl)phenyl ketene react to provide the intermediate ketene 645, which can cyclize to afford 2/7-pyran-2-ones in high yield (Scheme 150) <2004T5931>. Similarly, silyl enol ethers react with ot-(chlorocarbonyl)mesitylketene to afford 2//-pyran-2-ones (Equation 260) <2001T4133>. 

Silyl enol ethers are quite reactive towards IOB-boron trifluoride (or tetrafluoroboric acid) and can be considered as valuable starting materials for several reactions of synthetic importance. Of special interest is their use for carbon-carbon bond formation 1,4-diketones and unsaturated ketones are the products of such reactions further, they can be transformed to oc-hydroxy, methoxy or trifyloxy ketones. With tetrafluoroboric acid IOB forms a yellow solution containing the highly electrophilic Phi+ OH BF4 , stable up to 0°C. This species reacts readily with silyl ethers of several ketones, notably acetophenones, at —78°C, forming an unstable iodonium ion (ArCOCH2I+ Ph) which with another silyl ether affords 1,4-diketones. 

To a stirred suspension of IOB (220 mg, 1 mmol) in dichloromethane (5 ml) was added tetrafluoroboric acid in dimethyl ether (0.2 ml) at -50°C. The mixture was warmed to 0°C until formation of a yellow solution and then cooled to -78°C. To this the first silyl enol ether (1 mmol) was added with stirring. The cold reaction mixture was then added to a stirred solution of the second silyl enol ether (1 mmol) in dichloromethane (5 ml) at room temperature. After 10 min stirring, the reaction mixture was poured into water (50 ml) and extracted with dichloromethane (2 x 10 ml). The organic extract, after drying and concentration, yielded the crude diketone which was purified by column chromatography on silica gel (hexanes-ethyl acetate). When a silyl enol ether was treated with IOB.BF3 in the ratio 1 2, then the... 

Another carbon-carbon bond forming reaction mediated by (difluoroiodo)benzene-boron trifluoride was reported using silyl enol ethers which underwent oxidative dimerization to 1,4-diketones [58] (see also Sections 5.2.2 and 12.2.2). 

Another analogue of HTI which was used with either ketones or silyl enol ethers was [hydroxy(mesyloxy)iodo]benzene, PhI(OH)OS02Me [25]. A related reagent formed in situ from iodosylbenzene and trimethylsilyl triflate, probably PhI(OSiMe3)OTf, reacted similarly with silyl enol ethers to afford a-ketotriflates (see Table 5.3). /1-Diketones and /1-ketoesters underwent tosyloxylation by HTI the reaction was very effective in substrates with a perfluoroalkyl moiety and gave their hydrates [26] ... 

This reaction of cyclohexene with (PhI + )20 2BF4 and lithium perchlorate gave exclusively the cz s-bis-perchlorate adduct (92%). Also, silyl enol ethers underwent efficient oxidative coupling to 1,4-diketones [24] ... 

It has already been noted that the enolates of unactivated monocarbonyl compounds do not undergo alkynylation with alkynyliodonium salts3. It is therefore particularly intriguing that [bis(phenyliodonium)]ethyne ditriflate reacts with the silyl enol ether (SEE) of acetophenone to give an allenic diketone (equation 151)41. Except for the SEE of cyclohexanone, which gives a black tar with the bisiodonium compound41, similar studies of other SEEs have not been reported. 

The present method gives 3,3-dimethyl-l, 5-diphenylpentane-l,5-dione in better yield, and is widely applicable to the preparation of various 1,5-diketones.3 In addition, when silyl enol ethers of esters are employed instead of those of ketones, 6-keto esters can be obtained. ... 

If the 1,5-diearbonyl compound is required, then an aqueous work-up with either acid or base cleaves the silicon-oxygen bond in the product but the value of silyl enol ethers is that they can undergo synthetically useful reactions other than just hydrolysis. Addition of the silyl enol ether derived from aeetophenone (PhCOMe) to a disubstituted enone promoted by titanium tetrachloride is very rapid and gives the diketone product in good yield even though a quaternary carbon atom is created in the conjugate addition, This is a typical example of this very powerful class of conjugate addition reactions. 

Diketones Prepared from Silyl Enol Ethers and Nitroolefins... 

Silyl Enol Ether Nitroolefin Lewis Acid 1,4-Diketone Yield (%)... 

DIKETONES from silyl enol ethers AND NITROOLEFINS 117... 

SYNTHESIS OF 1,4-DIKETONES FROM SILYL ENOL ETHERS AND NITROOLEFINS 2-(2-OXOPROPYL)CYCLOHEXANONE... 

DIKETONES FROM SILYL ENOL ETHERS AND NITROOLEFINS 119... 

Preussomerin I 697 and ( )-preussomerin G 698 were obtained from 620 with a five- and six-steps sequence in 15% and 12% overall yield, respectively, through modifications of substituents of the dioxocin ring. Thus, attack of lithium methoxide from the less hindered face of the enone 620, followed by protection of the phenolic oxygen as its methyl ether provided the methoxy adduct 692. The ketone 693 was obtained through a benzylic bromination-solvolysis-oxidation protocol, which required only a single purification. The C(2)-C(3) olefin was introduced by selective silylation of the C-l carbonyl of diketone 693 and oxidation of the silyl enol ether with Pd(OAc)2. Enone... 

A-Diketones In the presence of excess tin(ll) triflate and a base (N-trimethyl-silylimidazole), P-keto aryl sulfoxides (excess) react with silyl enol ethers to provide 2-arylsulfenyl-1,4-diketones in moderate to high yield. 

Diketones y-keto esters. TiCU or SnCl4 activates nitroolefins for Michael addition with silyl enol ethers to form intermediate silyl nitronates, which are hydrolyzed to 1,4-diketones. 

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