Oxidation of enol acetate

Electrochemical oxidation of enol acetates in an undivided cell gives monomeric products in parallel with the reactions of simple alkenes [47, 48]. Thus, in the reaction of menthol enol acetate 23, the a-acetoxyketone product arises from nucleophilic attack of acetate ion on the radical-cation while the enone product... 

The oxidation of enol acetates of ketones to a-hydroxy (or a-acetoxy) ketones with the BTSP-FeCls system can also be performed . 

Scheme 8). For instance, the fluorination at the position a of ketones has been realized by the anodic oxidation of enol acetates (78) in an MeCN/Et3N-3HF/(Pt) system under potential control, giving a-fluoro ketone (79 equation 38). ... 

The oxidation of enol acetates in acetic acid containing tetraethylammonium p-toluenesulfonate gives four types of compounds (equation 23) conjugated enones (A), a-acetoxycarbonyl compounds (B), geminal diacetoxy compounds (C) and triacetoxy compounds (D). Similar to enol ethers, the Erst reactive intermediates are cation radicals generated from enol acetates by one-electron oxidation. The yields and the distribution of products A, B, C and D depend on the structure of the starting enol acetates and the reaction conditions. ... 

Tatsuya Shono, Shigenori Kashimura and Naoki Kise TABLE 4. Anodic oxidation of enol acetates... 

Hydroxyl groups are stable to peracids, but oxidation of an allylic alcohol during an attempted epoxidation reaction has been reported." The di-hydroxyacetone side chain is usually protected during the peracid reaction, either by acetylation or by formation of a bismethylenedioxy derivative. To obtain high yields of epoxides it is essential to avoid high reaction temperatures and a strongly acidic medium. The products of epoxidation of enol acetates are especially sensitive to heat or acid and can easily rearrange to keto acetates. 

Nitration of ketones or enol ethers provides a useful method for the preparation of a-nitro ketones. Direct nitration of ketones with HN03 suffers from the formation of a variety of oxidative by-products. Alternatively, the conversion of ketones into their enolates, enol acetates, or enol ethers, followed by nitration with conventional nitrating agents such as acyl nitrates, gives a-nitro ketones (see Ref. 79, a 1980 review). The nitration of enol acetates of alkylated cyclohexanones with concentrated nitric acid in acetic anhydride at 15-22 °C leads to mixtures of cis- and rrans-substituted 2-nitrocyclohexanones in 75-92% yield. 4-Monoalkylated acetoxy-cyclohexanes give mainly m-compounds, and 3-monoalkylated ones yield fra/w-compounds (Eq. 2.40).80... 

Because the a-nitroketones are prepared by the acylation of nitroalkanes (see Section 5.2), by the oxidation of (3-nitro alcohols (Section 3.2.3), or by the nitration of enol acetates (Section 2.2.5), denitration of a-nitro ketones provides a useful method for the preparation of ketones (Scheme 7.10). A simple synthesis of cyclopentenone derivatives is shown in Eq. 7.66.76... 

Again, the exclusive formation of six-membered rings indicates that the cyclization takes place by the electrophilic attack of a cationic center, generated from the enol ester moiety to the olefinic double bond. The eventually conceivable oxidation of the terminal double bond seems to be negligible under the reaction conditions since the halve-wave oxidation potentials E1/2 of enol acetates are + 1.44 to - - 2.09 V vs. SCE in acetonitrile while those of 1-alkenes are + 2.70 to -1- 2.90 V vs. Ag/0.01 N AgC104 in acetonitrile and the cyclization reactions are carried out at anodic potentials of mainly 1.8 to 2.0 V vs. SCE. 

Pattenden and Teague have prepared tricyclic diol 684 which is epimeric to the naturally occurring A < -capnellene-8p,10a-diol (68S) Their strategy, which is summarized in Scheme LXXI, encompasses two critical cyclization steps. The first is the Lewis acid-catalyzed ring closure of enol acetate 686 and the second involves reductive closure of acetylenic ketone 687. It is of interest that the oxidation of 688 proved to be stereospecific. 

The anodic oxidation of enol ethers at a graphite anode in methanol containing 2,6-lutidine and sodium perchlorate results in the dimerization of the enol ethers to acetals of 1,4-dica nyl compounds (equation 22). The mechanism of dimerization is thought to involve a tail-tail coupling of the cation radicals generated by the one-electron oxidation of the enol ethers. 

Since no evidence was provided in support of the above mechanistic proposals there is a priori no reason to exclude mechanism C as an alternative route to the observed products (see also Scheme 5). Interestingly, route C would also readily explain the observed regioselectivity in the oxidative cyclization reaction of enol acetates [221]. Some years later, however, Laurent and coworkers [226,227] demonstrated that in the presence of fluoride (CHjCN/EtsN, 3HF) enol acetate radical cations partially afforded rearrangement products (e.g. 141) not compatible with mechanism C. Rather, the products found suggest that fluoride adds directly to enol acetate radical cations providing the most stable radical intermediate (e.g. 140). 

The Mn(salen) complex 8 has also been appHed towards the synthesis of a-hydroxy carbonyl compounds from enol ethers and ketene acetals [87,88,89]. These substrates are a special class of trisubstituted olefins, previously demonstrated to be excellent substrates for AE. Indeed, the observed sense of stereoinduction in the oxidation of enol ether derivatives adheres to the skewed side-on approach model developed for trisubstituted olefins. In the presence of 7 mol % of 8, silyl enol ether 37 was oxidized under bleach conditions to afford the a-hy-droxy ketone in 87% ee (Scheme 14) [89]. 

A new synthesis of vinylphosphine oxides is available from the addition of secondary phosphine oxides to enol acetates to give (43), followed by thermolytic... 

Intramolecular enantiosituselectivity is exemplified by the biosynthetic formation of the mustard oil glucoside sinigrin (60) in horseradish, " the deprotonation of N-Boc-pyrrolidine (62) with sec-butyllithium (s-BuLi)/(-)-sparteine, followed by methylation, "" and, the oxidation of enol 64. Intermolecular enantiosituselective transformations are exemplified by the hydrolysis of racemic N-dodecanoylphenylalanine p-nitrophenyl esters (( )-67) in the presence of tripeptide catalyst (Z)-L-Phe-L-His-L-Leu (68) in each of the latter two cases, only one (externally) enantiotopic carbonyl reacts preferentially. It should be pointed out parenthetically, that as a result of the enantiosituselectivity in these transformations, one has, in effect, kinetic resolution of ( )-67. The electron-impact induced elimination in acetate 71, and the oxidation of 73 exemplify intramolecular diastereosituselective transformations. The epoxidation of the mixture 76/77 is an example of an intermolecular diastereosituselective process at the same time that each substrate is subject to enantiositunonselectivity of the carbonyl sub-sites. 

In 2010, the Sato group disclosed the synthesis of tetrodotoxin 86 starting from d-glucose, in which the Perrier carbocyclization of enol acetate 92 was employed for the construction of the cyclohexane core of tetrodotoxin. 4,6-O-Benzylidene derivative 99 was converted into pyranoside 93 possessing an exo-methylene group at C-3 (Scheme 12.47). m-CPBA oxidation of 93 stereoselectively provided epoxide 183. Alkaline hydrolysis of the epoxide in 183 followed by acetonide formation gave primary alcohol 184. Oxidation of 184 afforded aldehyde 185, which was converted into (Z)-enol acetate 92 by the action of acetic anhydride and potassium carbonate. When enol acetate 92 reacted with Hg(OAc)2, followed by NaCl treatment, the Perrier carbocyclization reaction successfully took place to afford a mixture of... 

A new facile synthesis of a-iodo-ketones involves oxidation of alkenes using silver chromate and iodine [equation (48)], while thallium(iii) acetate and iodine are effective for the conversion of enol acetates into a-iodo-ketones. 

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],... 

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