Ketones enol ether synthesis

Jauch, J. Stereochemistry of the Rubottom oxidation with bicyclic silyl enol ethers synthesis and dimerization reactions of bicyclic a-hydroxy ketones. Tetrahedron 1994, 50,12903-12912. 

Unique successful hydroxylations with ozone and mCPBA First Successful Method Epoxidation of Silyl Enol Ethers (Rubottom Oxidation) Method, mechanism, and isolation of intermediates Chemo- regio- and stereoselectivity synthesis of fused y-laclones Hydroxylation of Amino-ketones via Silyl Enol Ethers Synthesis of vinca alkaloids and model compounds... 

The aldol condensation is a very attractive route to a,p-unsaturated carbonyl compounds. The application of this reaction is nevertheless rather limited, since numerous side reactions usually occur amongst these are self-condensation of the ketone, Michael-type addition to the newly formed product, or Cannizzaro reactions. As a consequence, poor yields are obtained in most cases [90]. In the enol ether condensation, described earlier, these side reactions are less troublesome. A disadvantage of the enol ether condensation compared to the aldol condensation is that strongly acidic conditions have to be used to cleave the intermediate in the enol ether synthesis. 

The concept of silyl enol ether synthesis via / -elimination from a Brook rearrangement-derived carbanion also appeared in Wicha s studies on additions of 1-phenyl-l//-tetrazol-5-yl (PT) sulfonyl anions to acyl silanes. When PT sulfone 34 was deprotonated in the presence of acyl(triphenyl)silane, ketone 36 was isolated in good yield after hydrolysis of the silyl enol ether intermediate 35. The mechanism involved addition of the... 

Enol Ether Synthesis. A 2-(trimethylsilyl)ethyl-based dithioorthoformate was prepared via copper(II) bromide-promoted oxidative coupling of bis(phenylthio)-methyltributylstannane. The dithioorthoformate thus prepared is treated with a titanocene(II) reagent followed by the addition of ketones or esters to promote alkoxymethylidenation as exemplified in eq 32. ... 

Addition of a hydroxy group to alkynes to form enol ethers is possible with Pd(II). Enol ether formation and its hydrolysis mean the hydration of alkynes to ketones. The 5-hydroxyalkyne 249 was converted into the cyclic enol ether 250[124], Stereoselective enol ether formation was applied to the synthesis of prostacyclin[131]. Treatment of the 4-alkynol 251 with a stoichiometric amount of PdCl2, followed by hydrogenolysis with formic acid, gives the cyclic enol ether 253. Alkoxypalladation to give 252 is trans addition, because the Z E ratio of the alkene 253 was 33 1. 

The synthesis of polymethines with dimethylene bridges starts with aUcychc ketones (31), ketals (32), and enamines (X = NR2), or enol ethers (X = OR) (33). They possess two activated centers, methine or methylene groups, which react with Vilsmeief s reagent to produce the corresponding dyes. 

Silylated cyanohydrins have also been prepared via silylation of cyanohydrins themselves and by the addition of hydrogen cyanide to silyl enol ethers. Silylated cyanohydrins have proved to be quite useful in a variety of synthetic transformations, including the regiospecific protection of p-quinones, as intermediates in an efficient synthesis of a-aminomethyl alcohols, and for the preparation of ketone cyanohydrins themselves.The silylated cyanohydrins of heteroaromatic aldehydes have found extensive use as... 

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]... 

Schemes 3-7 describe the synthesis of cyanobromide 6, the A-D sector of vitamin Bi2. The synthesis commences with an alkylation of the magnesium salt of methoxydimethylindole 28 to give intermediate 29 (see Scheme 3a). The stereocenter created in this step plays a central role in directing the stereochemical course of the next reaction. Thus, exposure of 29 to methanol in the presence of BF3 and HgO results in the formation of tricyclic ketone 22 presumably through the intermediacy of the derived methyl enol ether 30. It is instructive to point out that the five-membered nitrogen-containing ring in 22, with its two adjacent methyl-bearing stereocenters, is destined to become ring A of vitamin Bi2. A classical resolution of racemic 22 with a-phenylethylisocyanate (31) furnishes tricyclic ketone 22 in enantiomerically pure form via diaster-eomer 32.

The enol ethers of P-dicarbonyl compounds are reduced to a, 3-unsaturated ketones by LiAlH4, followed by hydrolysis.115 Reduction stops at the allylic alcohol, but subsequent acid hydrolysis of the enol ether and dehydration leads to the isolated product. This reaction is a useful method for synthesis of substituted cyclohexenones. 

Rawal and Kozmin have utilized a Reissert type reaction in the total synthesis of tabersonine. The requisite nitro ketone is prepared by SNAr reaction of o-nitrophenylphenyliodonium fluoride with ketone silyl enol ether (Scheme 10.10).96... 

The oxidation of enol ethers and their derivatives is a useful method for the synthesis of a-hydroxy-ketones or their derivatives, which are versatile building blocks for organic synthesis. Since enol ethers and esters are types of olefin, some asymmetric epoxidation and dihydroxylation reactions have been applied to their oxidation. 

Silyl enol ethers of alkenyl methyl ketones can be efficiently cyclized to cyclopentenones and cyclohexenones by treating them with stoichiometric amounts of palladium acetate244 an example indicating the elaboration of this approach to the synthesis of a reduced benzoxepinone derivative, and the suggested244 mechanism of the reaction, are depicted in Scheme 174. 

A facile synthesis of 5-substituted 3-aminopyrrole-2-carboxylates has been developed wherein condensation of diethyl aminomalonate with a-cyano ketones 46 was facilitated by prior formation of the p-toluenesulfonyl enol ether 47 <00JOC2603>. Addition of the amine component is followed by cyclization and decarboxylation to afford the pyrroles 48. 

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. 

Regiospecific mono-C-alkylation (60-90%) of trimethylsilyl enol ethers is promoted by benzyltriethylammonium fluoride [34, 35]. A similar alkylation of tin(IV) enolates is aided by stoichiometric amount of tetra-n-butylammonium bromide and has been utilized in the synthesis of y-iminoketones [36]. Carbanions from weakly acidic carbon acids can be generated by the reaction of their trimethylsilyl derivatives with tetra-n-butylammonium triphenyldifluorosilicate [37] (see also Section 6.3). Such carbanions react readily with haloalkanes. Tautomeric ketones in which the enol form has a high degree of stabilization are O-alkylated to form the enol ether, e.g. methylation of anthrone produces 9-methoxyanthracene [26],... 

---