1.5- Dicarbonyl compounds from silyl enol ethers

Dicarbonyl compounds are formed from the reaction of silyl enol ethers with methyl vinyl ketones in the presence of BF3 OEt2 and an alcohol (eq 9). a-Methoxy ketones are formed from a-diazo ketones with BF3-OEt2 and methanol, or directly from silyl enol ethers using iodobenzene/BF3-OEt2 in methanol. ... 

The TiCU-promoted Michael reaetion proceeds under very mild conditions (—78 °C) this suppresses side-reactions and 1,5-dicarbonyl compounds are formed in good yields. For TiCU-sensitive compounds, a mixture of TiCU and Ti(0-/-Pr)4 is used. From silyl enol ethers and a,p-unsaturated ketones, 1,5-dicarbonyl compounds are formed (eq 32). The reaction also proceeds for a,p-unsaturated acetals. Silylketene acetals react with a,p-unsaturated ketones or their acetals to form 8-0x0 esters (eq 33). ... 

The asymmetric allylic C-H activation of cyclic and acyclic silyl enol ethers furnishes 1,5-dicarbonyl compounds and represents a surrogate of the Michael reaction [136]. When sufficient size discrimination is possible the C-H insertion is highly diastereoselective, as in the case of acyclic silyl enol ether 193 (Eq. 22). Reaction of aryldia-zoacetate 192 with 193 catalyzed by Rh2(S-DOSP)4 gives the C-H insertion product 194 (>90% de) in 84% enantiomeric excess. A second example is the reaction of the silyl enol ether 195 with 192 to form 196, a product that could not be formed from the usual Michael addition because the necessary enone would be in its tautomeric naphthol form (Eq. 23). 

While fluoroxy compounds react well with enol derivatives, fluorine in general does not. However, there are various reports where such reactions are described and in certain cases even with decent yields. In 1982 it was reported that pyruvates with a dominant enolic form react well with fluorine, to give the corresponding fluoro derivatives l.78 Several silyl enol ethers 2 and 379 including ones made from 1,3-dicarbonyl derivatives 480 react quite satisfactorily with fluorine to give the expected a-fluoro ketones. Steroidal 16-enol acetates react with fluorine to form mainly 16a-fluoro-17-oxo steroids e.g. 5.81... 

The kinetic reprotonation by a series of carbonyl-based acids, of the lithium enolate obtained from 2,4-dimethyltetralone either by LDA-mediated deprotonation or by cleavage of its silyl enol ether, was studied by Eames (Scheme 71)352. The diastereoselective ratio, close to the thermodynamic value, obtained with methanol (pKa = 29 in DMSO) is probably due to equilibration. The difference observed in the presence of an additive was interpreted as the result of a fine balance between the coordinating ability, the intrinsic acidity, and probably the concentration of the enolic form of the cyclic and linear dicarbonyl acidic compounds. 

Treatment of 1,3-dicarbonyl compounds with DBP in a methoxide/methanol system affords 2-alkyl-4-[(phenylsulfonyl)methyl]furans, where reaction proceeds by Initial addition-elimination on the vinyl sulfone moiety. In contrast, silyl enol ethers in the presence of silver tetrafluoroborate resulted in products derived from Sn2 displacement at the allylic site.11 Anions derived from 1,3-dicarbonyls substituted at the C-2 position are found to induce a complete reversal in the mode of ring closure.12 The major products obtained are 3-[(phenylsulfonyl)methyl]-substituted cyclopentenones. The internal displacement reaction leading to the furan ring apparently encounters an unfavorable Ai -interaction in the transition state when a substituent group is present at the 2-position ol the dicarbonyl compound. This steric Interaction is not present in the transition state leading to the cyclopentenone ring. 

Michael reactions of silyl enolates or ketene silyl acetals with a, -unsaturated carbonyl compounds are among the most important carbon-carbon bond-forming processes in organic synthesis. Sc(OTf)3 was found to be effective [4], and the reactions proceeded smoothly in the presence of a catalytic amount of Sc(OTf)3, under extremely mild conditions, to give the corresponding 1,5-dicarbonyl compounds in high yields after acid work-up (Eq. 2). Silyl enolates derived from ketones, thioesters, and esters were applicable, and no 1,2-addition products were obtained. The products could, furthermore, be isolated as synthetically valuable silyl enol ethers (I) when acid-free work-up was performed. The catalyst could be recovered almost quantitatively and could be re-used. 

If the 1,5-dicarbonyl 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 acetophenone (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. 

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]. 

Symmetrical 1,5- diketones may be prepared by addition of a THF solution of a ketone lacking a1 - hydrogens to a solution of potassium in DMF - THF the central methylene appears to derive from the formal carbon of dimethylformamide [equation (42)].143 A more general preparation of 1,5- dicarbonyl compounds uses the boron trifluoride etherate catalysed reaction of silyl enol ethers with 3-methoxyallyl alcohols in nitromethane [equation (43)]. The... 

Fluorination of Enolates and Silyl Enol Ethers. iV-fluoro-Af-(phenylsulfonyl)henzenesulfonamide (1) can be used successfully to prepare a-fluorocarbonyl compounds starting from esters, ketones, or 8-dicarbonyl precursors by electrophilic fluorination of the corresponding enolates (eqs 1-3) or silyl enol ethers (eq 4). Diastereoselective fluorination of enolates with 1 has recently been reported. ... 

Indeed, photoredox catalysis with Ru polypyridine complexes has emerged as a powerful tool for redox reactions including formation of carbon-carbon bonds based on oxidation of sp C-H bonds via single-electron-transfer (SET) processes. Results that are closely related to those shown in Schemes 33,34, and 35, where the carbon-carbon bond formation resulted from the benzyUc sp C-H oxidative activation in the presence of BuOOH, have been recently reported for the regioselective functionalization of tetrahydroisoquinolines with cyanide and a variety of nucleophiles arising from ketones, nitroalkanes, allyltrimethylsilane, silyl enol ethers, 1,3-dicarbonyl compounds under photocatalytic conditions [67-70] as illustrated in Scheme 62 [67]. Other applications of Ru(bipy)3Cl2 in photocatalytic cycUzation reactions involving carbon-carbon btmd formation have appeared [71, 72]. 

Scheme 7.46) [77]. The reaction was applicable to the synthesis of a-ethenyl ke- tones possessing acidic a-protons, and isomerization to the thermodynamically stable conjugated enone was not observed. Equatorial preferences were observed in the ethenylation of cyclohexanone enolates for example, the ethenylation of a silyl enol ether derived from trans-3-decalone predominantly gave an equatorial isomer (Scheme 7.47) [78]. Silyl dienolates, synthesized by the a-ethenylation of thioesters followed by silylation, were ethenylated by this method at the a-position [79]. Ethenylation also occurred with silylated 1,3-dicarbonyl compounds, and ethenylmalonate possessing an acidic a-proton was obtained (Scheme 7.48) [80]. 

Dicarbonyl compounds.1 The reaction of enol silyl ethers with methyl vinyl ketone catalyzed by BF3 etherate results in 1,5-dicarbonyl compounds. Almost quantitative yields can be obtained, even from hindered ketones, by addition of an alcohol or even, to a less extent, of water. 

Interesting heteroatom-substituted derivatives such as 67 have also been synthesized via the reaction of bis enol ether 66 with thiol-containing dicarbonyl electrophiles, Eq. 54 [81]. Compound 68 bearing a bridgehead silyl substituent was produced from the reaction of 65 with a ketoacylsilane [82], Subsequent decarboxylation and desilylation of 68 generates 69, Eq. 55. The overall sequence represents a method to obtain the product of a formal inversion of the usual reactivity of 65 with ketoaldehydes. Extensive studies failed to reverse the observed regio selectivity. 

Arisawa, M., Ramesh, N.G., Nakajima, M., Tohma, H., and Kita, Y, Hypervalent iodine(lll)-induced intramolecular cychzation of a-(aryl)alkyl-P-dicarbonyl compounds a convenient synthesis of benzarmulated and spirobenzannulated compounds, /. Org. Chem., 66, 59, 2001. Eberson, L., Reaction between organic and metal ion species, in Electron Transfer Reactions in Organic Chemistry, Reactivity and Structure, Vol. 25, Hafner, K., Lehn, J.-M., Rees, C.W., von Rague-Schleyer, R, Trost, B.M., and Zahradnik, R, Eds., Springer-Verlag, Berhn, 1987, chap. 7. Bockman, T.M., ShuMa, D., and Kochi, J.K., Photoinduced electron transfer from enol silyl ethers to quinone. Part 1. Pronounced effects of solvent polarity and added salt on the formation of a-enones, J. Chem. Soc., Perkin Trans. 2, 1623, 1996. 

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