Ethers, enol oxidation

Oxidation of silyl enol ethers. Oxidation of silyl enol ethers to a-hydroxy aldehydes or ketones is usually effected with w-chloroperbenzoic acid (6, 112). This oxidation can also be effected by epoxidation with 2-(phenylsulfonyl)-3-( p-nitrophenyl) oxaziridine in CHC1, at 25-60° followed by rearrangement to a-silyloxy carbonyl compounds, which are hydrolyzed to the a-hydroxy carbonyl compound (BujNF or H,0 + ). Yields are moderate to high. Oxidation with a chiral 2-arene-sulfonyloxaziridine shows only modest enantioselectivity. 

Others [180,260]). In general, enol radical cations may be obtained from either direct oxidation of stable ends or by selective oxidation of the enol tautomer of the keto/enol equilibrium. In addition it has been outlined that enol radical cations offer an access to a-carbonyl radical chemistry. Other enol systems like silyl enol ethers, enol esters and enolates similarly may open up after oxidation the chemistry of a-carbonyl radical or a-carbonyl cation intermediates, whereas enol ether oxidative a-functionalization reactions work by another route. 

The methyl enol ether 37 is oxidized to the a,/3-unsaturated aldehyde 39 via hemiacetal 38. Unsaturated aldehyde 39, elongated one carbon from the aldehyde 36, is prepared by the Wittig reaction of 36 to give 37, and application of this reaction[ 88]. 

The oxidation of the cyclic enol ether 93 in MeOH affords the methyl ester 95 by hydrolysis of the ketene acetal 94 formed initially by regioselective attack of the methoxy group at the anomeric carbon, rather than the a-alkoxy ketone[35]. Similarly, the double bond of the furan part in khellin (96) is converted ino the ester 98 via the ketene acetal 97[l23],... 

The 7, i5-unsaturated alcohol 99 is cyclized to 2-vinyl-5-phenyltetrahydro-furan (100) by exo cyclization in aqueous alcohol[124]. On the other hand, the dihydropyran 101 is formed by endo cyclization from a 7, (5-unsaturated alcohol substituted by two methyl groups at the i5-position. The direction of elimination of /3-hydrogen to give either enol ethers or allylic ethers can be controlled by using DMSO as a solvent and utilized in the synthesis of the tetronomycin precursor 102[125], The oxidation of the optically active 3-alkene-l,2-diol 103 affords the 2,5-dihydrofuran 104 in high ee. It should be noted that /3-OH is eliminated rather than /3-H at the end of the reac-tion[126]. 

The Pd-catalyzed elimination of the mesylate 909 at an anomeric center, although it is a saturated pseudo-halide, under mild conditions is explained by the facile oxidative addition to the mesylate C—O bond, followed by elimination of /3-hydrogen to give the enol ether 910[767],... 

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... 

A carbonyl group cannot be protected as its ethylene ketal during the Birch reduction of an aromatic phenolic ether if one desires to regenerate the ketone and to retain the 1,4-dihydroaromatic system, since an enol ether is hydrolyzed by acid more rapidly than is an ethylene ketal. 1,4-Dihydro-estrone 3-methyl ether is usually prepared by the Birch reduction of estradiol 3-methyl ether followed by Oppenauer oxidation to reform the C-17 carbonyl function. However, the C-17 carbonyl group may be protected as its diethyl ketal and, following a Birch reduction of the A-ring, this ketal function may be hydrolyzed in preference to the 3-enol ether, provided carefully controlled conditions are employed. Conditions for such a selective hydrolysis are illustrated in Procedure 4. 

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. 

Steroidal 17-cyanohydrins are relatively stable towards chromium trioxide in acetic acid (thus permitting oxidation of a 3-hydroxyl group ) and towards ethyl orthoformate in ethanolic hydrogen chloride (thus permitting enol ether formation of a 3-keto-A system ). Sodium and K-propanol reduction produces the 17j -hydroxy steroid, presumably by formation of the 17-ketone prior to reduction. ... 

The 2,2 -bis(phenylthiomethyl) dispiroketal (dispoke) derivative is cleaved by oxidation to the sulfone, followed by treatment with LiN(TMS)2. The related bromo and iodo derivatives are cleaved reductively with LDBB (lithium 4,4 -di- -butylbiphenylide) or by elimination with the P4- -butylphosphazene base and acid hydrolysis of the enol ether. The 2,2-diphenyl dispiroketal is cleaved with FeCl3 (CH2CI2, rt, overnight)." The dimethyl dispiroketal is cleaved with TFA, and the allyl derivative is cleaved by ozonolysis followed by elimination. ... 

Alkyl-1,4-dihydropyridines on reaction with peracids undergo either extensive decomposition or biomimetic oxidation to A-alkylpyridinum salts (98JOC10001). However, A-methoxycarbonyl derivatives of 1,4- and 1,2-dihydro-pyridines (74) and (8a) react with m-CPBA to give the methyl tmns-2- 2>-chlorobenzoyloxy)-3-hydroxy-1,2,3,4-tetrahydropyridine-l-carboxylate (75) and methyl rran.s-2-(3-chlorobenzoyloxy)-3-hydroxy-l,2,3,6-tetrahydropyridine-l-carboxylate (76) in 65% and 66% yield, respectively (nonbiomimetic oxidation). The reaction is related to the interaction of peracids with enol ethers and involves the initial formation of an aminoepoxide, which is opened in situ by m-chlorobenzoic acid regio- and stereoselectively (57JA3234, 93JA7593). 

Oppenauer oxidation of the enol ether (34) affords the corresponding 17 ketone (37) (the enol ether is stable to the basic oxidation conditions). This ketone affords the corresponding 17a-ethynyl compound on reaction with metal acetylides. Hydrolysis of the enol ether under mild conditions leads directly... 

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