Esters enol ethers

Reactions of Enol Esters, Ethers, and Enamines.—Under conditions of kinetic control, hydrolysis of the enol acetate of a 6-methyloestr-4-en-3-one gives the 6a-methyl-4-en-3-one, although prolonged reaction gives an equilibrated mixture of the 6a- and 6 -methyl isomers (p. 283). ° Acidic hydrolysis of 3)S-acetoxy-4-methoxycholest-4-ene (348) appears to occur via loss of the allylic 3j3-substituent, in preference to protonation of the enol ether at C-5. The allylic cation (349) is attacked by water at C-5, and subsequent hydrolysis of the enol ether (350) affords 5-hydroxy-5)3-cholestan-4-one (351). The isomeric 4)8-acetoxy-enol ether (352) is hydrolysed normally, giving a 3-oxo-product (353). ... 

Heck, R.F. (1968) The palladium-catalyzed arylation of enol esters, ethers, and halides. A new synthesis of 2-aryl aldehydes and ketones. J. Am. Chem. Soc., 90, 5535-8. 

Low molecular mass enol esters (e.g. acetates H.O. House, 1965) or enol ethers (e.g. silyl ethers H.O. House, 1969) of ketones can be synthesized regioselectively and/or separated by distillation. Treatment with lithium alkyls converts them into the corresponding lithi-... 

In 1959 Carboni and Lindsay first reported the cycloaddition reaction between 1,2,4,5-tetrazines and alkynes or alkenes (59JA4342) and this reaction type has become a useful synthetic approach to pyridazines. In general, the reaction proceeds between 1,2,4,5-tetrazines with strongly electrophilic substituents at positions 3 and 6 (alkoxycarbonyl, carboxamido, trifluoromethyl, aryl, heteroaryl, etc.) and a variety of alkenes and alkynes, enol ethers, ketene acetals, enol esters, enamines (78HC(33)1073) or even with aldehydes and ketones (79JOC629). With alkenes 1,4-dihydropyridazines (172) are first formed, which in most cases are not isolated but are oxidized further to pyridazines (173). These are obtained directly from alkynes which are, however, less reactive in these cycloaddition reactions. In general, the overall reaction which is presented in Scheme 96 is strongly... 

Generally, isolated olefinic bonds will not escape attack by these reagents. However, in certain cases where the rate of hydroxyl oxidation is relatively fast, as with allylic alcohols, an isolated double bond will survive. Thepresence of other nucleophilic centers in the molecule, such as primary and secondary amines, sulfides, enol ethers and activated aromatic systems, will generate undesirable side reactions, but aldehydes, esters, ethers, ketals and acetals are generally stable under neutral or basic conditions. Halogenation of the product ketone can become but is not always a problem when base is not included in the reaction mixture. The generated acid can promote formation of an enol which in turn may compete favorably with the alcohol for the oxidant. 

Photochemical rearrangements of enol esters, enol lactones, and enol ethers... 

With respect to the olefinic substrate, various functional groups are tolerated, e.g. ester, ether, carboxy or cyano groups. Primary and secondary allylic alcohols, e.g. 14, react with concomitant migration of the double bond, to give an enol derivative, which then tautomerizes to the corresponding aldehyde (e.g. 15) or ketone ... 

Due to the nonaromatic character of the oxepin system the oxepinones do not usually form stable enol structures. By O-acylation or O-alkylation, however, the enol forms can be stabilized as enol esters and ethers, respectively. A large number of substituted 1-benzoxepins have been synthesized by this route. Acetylation of l-benzoxepin-3(2//)-ones 1 and l-benzoxepin-5(2/T)-ones 3 was readily achieved with acetic anhydride in the presence of an appropriate base such as pyridine, triethylamine or sodium acetate.t5,t6 t72 176... 

Dimethyldioxirane DMDO discovered by Murray and coworkers, is a superior choice for the epoxidation of most olefins, giving comparable or higher yields than m-CPBA-based epoxidation [21]. Proceeding rapidly under neutral and mild conditions, it is especially well suited for the synthesis of sensitive epoxides of enol esters, enol lactones [22], and enol ethers [23]. The reaction is stereospecific, gen-... 

Enolizable compounds can be used for Meerwein reactions provided that the keto-enol equilibrium is not too far on the side of the ketone for example, P-dicar-bonyl compounds such as acetylacetone are suitable (Citterio and Ferrario, 1983). The arylation of enol esters or ethers (10.12) affords a convenient route for arylating aldehydes and ketones at the a-carbon atom (Scheme 10-48). Silyl enol ethers [10.12, R = Si(CH3)3] can be used instead of enol ethers (Sakakura et al., 1985). The reaction is carried out in pyridine. 

The acid-catalyzed hydrolysis of enol esters (RCOOCR =CR) can take place either by the normal Aac2 mechanism or by a mechanism involving initial protonation on the double-bond carbon, similar to the mechanism for the hydrolysis of enol ethers given in 10-6, ° depending on reaction conditions. In either case, the products are the carboxylic acid RCOOH and the aldehyde or ketone R2" CHCOR. ... 

See Section 362 (Ester-Alkene) for the formation of enol esters and Section 367 (Ether-Alkenes) for the formation of enol ethers. Many of the methods in Section 60A (Protection of Aldehydes) are also applicable to ketones. 

With trimethylsilyl iodide 17 the 0,N-acetal 457 gives the iminium iodide as reactive intermediate this converts the enol silyl ether 107 a in situ into the Man-nich-base 669, in 81% yield, and hexamethyldisiloxane 7 [195]. On treatment of the 0,N-acetal 473 (or the N-silylated Schiff base 489) with TMSOTf 20 (or Zny, the intermediate iminium triflate adds to the ketene acetal 663 to give mefhoxytri-methylsilane 13 a and silylated / -amino esters such as 670, which are readily transsilylated by methanol to give the free / -aminoester [70, 196] (Scheme 5.61). 

Fe(OTf)2-catalyzed aziridination of enol silyl ethers with PhlNTs followed by ring opening led to a-N-tosylamido ketones in good yields (Scheme 27) [81]. With silyl ketene ketal (R = OMe) as substrate, the N-tosyl-protected amino acid ester was obtained in 50% yield. In contrast, the copper (I) salt CuClOq was found not effective for this substrate [82]. 

Combined use of Co(acac)2 and DiBAlH also gives selective reduction for a,(3-unsaturated ketones, esters, and amides.112 Another reagent combination that selectively reduces the carbon-carbon double bond is Wilkinson s catalyst and triethylsilane. The initial product is the enol silyl ether.113... 

When this reaction sequence is applied to enol esters or enol ethers, the result is a-oxygenation of the starting carbonyl compound. Enol acetates form epoxides that rearrange to a-acetoxyketones. 

In 1992, Thornton et al. reported that Mn(salen) (43) catalyzed the asymmetric oxidation of silyl enol ethers to give a mixture of a-siloxy and a-hydroxy ketones, albeit with moderate enantioselectivity (Scheme 28).135 Jacobsen et al. examined the oxidation of enol esters with Mn(salen) (27) and achieved good enantioselectivity.136 Adam et al. also reported that the oxidation of enol ethers with (27) proceeded with moderate to high enantioselectivity.137 Good substrates for these reactions are limited, however, to conjugated enol ethers and esters. Based on the analysis of the stereochemistry,137 enol ethers have been proposed to approach the oxo-Mn center along the N—Mn bond axis (trajectory c, vide supra). 

Ferraris et al.108 demonstrated an asymmetric Mannich-type reaction using chiral late-transition metal phosphine complexes as the catalyst. As shown in Scheme 3-59, the enantioselective addition of enol silyl ether to a-imino esters proceeds at —80°C, providing the product with moderate yield but very high enantioselectivity (over 99%). 

Following their success with chiral ketone-mediated asymmetric epoxidation of unfunctionalized olefins, Zhu et al.113 further extended this chemistry to prochiral enol silyl ethers or prochiral enol esters. As the resultant compounds can easily be converted to the corresponding a-hydroxyl ketones, this method may also be regarded as a kind of a-hydroxylation method for carbonyl substrates. Thus, as shown in Scheme 4-58, the asymmetric epoxidation of enol silyl... 

A different approach towards titanium-mediated allene synthesis was used by Hayashi et al. [55], who recently reported rhodium-catalyzed enantioselective 1,6-addition reactions of aryltitanate reagents to 3-alkynyl-2-cycloalkenones 180 (Scheme 2.57). In the presence of chlorotrimethylsilane and (R)-segphos as chiral ligand, alle-nic silyl enol ethers 181 were obtained with good to excellent enantioselectivities and these can be converted further into allenic enol esters or triflates. In contrast to the corresponding copper-mediated 1,6-addition reactions (Section 2.2.2), these transformations probably proceed via alkenylrhodium species (formed by insertion of the C-C triple bond into a rhodium-aryl bond) and subsequent isomerization towards the thermodynamically more stable oxa-jt-allylrhodium intermediates [55],... 

In the case of ethyl acetoacetate we thus deduce, by reference to the table, that in water the keto-ester should be the more soluble, and in petrol ether the enol-ester this is actually the case. 

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