Acetoxy-ketones, from enols

Lead tetraacetate can effect oxidation of carbonyl groups, leading to formation of a-acetoxy ketones,215 but the yields are seldom high. Boron trifluoride can be used to catalyze these oxidations. It is presumed to function by catalyzing the formation of the enol, which is thought to be the reactive species.216 With unsymmetrical ketones, products from oxidation at both a-methylene groups are found.217... 

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... 

Despite the fact that the electrochemical oxidation of most of the nonconjugated dienes generally does not give products which result from interaction of the double bonds with one another, the anodic oxidation l-acetoxy-l,6-heptadienes gives intramolecularly cyclized products, that is, the cyclohexenyl ketones (equation 15)13. The cyclization takes place through the electrophilic attack of the cation generated from enol ester moiety to the double bond. 

Hydrolysis of Enol Esters. Enzyme-mediated enantioface-differentiating hydrolysis of enol esters is an original method for generating optically active a-substituted ketones (84—86). If the protonation of a double bond occurs from one side with the simultaneous elimination of the acyl group (Fig. 3), then the optically active ketone should be produced. Indeed, the incubation of l-acetoxy-2-methylcyclohexene [1196-73-2] (68) with Pichia... 

The elimination reactions of /l-acetoxy sulfones 114 to give the donor-acceptor-substituted allenes 115 by a Julia-Lythgoe process are less conventional (Scheme 7.18) [157]. A new one-step synthesis of allene-l,3-dicarboxylates 118 from acetone derivatives 116 was developed by the use of 2-chloro-l,3-dimethylimidazolinium chloride 117 [158, 159]. This elimination of water follows also the general Scheme 7.17 if a derivative of the enol, resulting from 116, is assumed as an intermediate for an elimination step. More complex processes of starting materials 119 furnished allenyl ketones 120 in high yields [160-162]. 

Diazomethane furnishes the methyl ether which has been degraded to 3-methoxyfuran which, however, is more easily available from 3-iodofuran. 3-Methoxyfuran is cleaved by acid to furan-3(2H)-one. Other 3-furanols with ester, acetyl or benzoyl substituents at the 2-position are also available. They exist in the enolic form but their chemistry has not been investigated (76JCS(P1)1688>. Furan-3(2H)-ones with acetyl or ester substituents at the 4-position are readily available. They exist in the keto form but show some evidence for enolic behaviour and their chemistry is similar to that of enolizable ketones. They enter into cycloaddition with maleic anhydride, are alkylated at the 2-position, condense with aldehydes and ketones and are oxidized by LTA to the 2-acetoxy compounds (74BSF2061). 

Benzofuran-3(2/f)-ones (396) exist in the keto form but undergo ready enolization. Acetylation with acetic anhydride and sodium acetate affords 3-acetoxybenzo[6]furans, but reaction under acidic conditions usually supplies these products admixed with 3-acetoxy-2-acetylbenzo[6]furans. Alkylation usually furnishes a mixture of O- and C-alkylated products. 3-Acetoxy-6-methoxy-4-methylbenzo[6]furan, on Vilsmeier reaction, supplies the 3-chlorobenzo[6]furan-2-carbaldehyde, the product expected from an enolizable ketone (72AJC545). Benzofuran-3(2//)-ones react normally with carbonyl reagents. Grignard reagents react in the expected way and dehydration of the intermediate affords a 3-substituted benzo[6]furan. The methylene group is reactive so that self condensation, condensation with aldehydes and ketones and reaction with Michael acceptors all occur readily. 

While enol acetates from saturated ketones were useful a-oxygenation substrates, the corresponding dienol acetates are not. The relatively electron-deficient alkene bearing the acetoxy group is less attractive h> elecm hilic oxygenating agents than the unsubstituted double bond. Thus, for example, peracid treatment leads to epoxidation the unfiinctionalized alkene.However, it would seem likely that re-... 

An earlier report [i8y] of the formation of 4a-acetoxy-cholest"5"en-3 One (4) from cholest-5-en-3-one (3) can now be interpreted as a preferential a-face attack upon the enolic 3,5-diene. The stereochemistry of acetoxylation suggests a connection with the sterically-controlled 4 -deprotonation of the A -3-ketone discussed in Chapter 4, section 6, but electrophilic attack at C<4) rather than at C 6> in the neutral enol is abnormal, and probably indicates that acetoxy transfer occurs via a cyclic transition state (3 with the reagent bonded to the C(3)-oxygen substituent. Corey [188] has proposed a mechanism of this type, and suggested that the enol triacetoxy-plumbate cf. 5) may arise by direct reaction between the ketone and the reagent. Supporting such an interpretation, the 3-acetoxy 3,5 diene(6) reacted normally (p. 184) with lead tetraacetate to give the 6j -acetoxy-A -3-ketone 7) [i8g] instead of a 4-acetoxy derivative. 

Enolic derivatives of other ketones, e.g. enol acetates of saturated C(3> and C 20> ketones, have been converted into a -substituted ketones by some of the reagents listed in Table 19, but the reactions do not warrant special mention. Lead tetraacetate has been employed for the introduction of 16-acetoxy groups by attack on A -enol acetates of androstan-17-ones [2i8,2ig]. The products are i6 9-acetoxy 17-ketones, in contrast to the i6a-configuration of bromination products from the same enol acetates. As i6j8-derivatives are the more stable isomers, it seems likely that the reaction involves initial a-attack followed by epimerisation. The enol acetate of a i4jS-i7 ketone likewise gives the more stable iba-acetoxy-iy-ketone [2ig]. 

Trapping of the Beckmann intermediates with enol silyl ethers affords facile entry to a variety of en-amino ketones. This condensation takes place with retention of regiochemical integrity in both oxime sulfonates and enol silyl ethers. Reaction of 6-methyl-l-(trimethylsiloxy)-l-cyclohexene (41) or 1-methyl-2-(trimethylsiloxy)-l-cyclohexene (42) with cyclohexanone oxime mesylate furnishes (43) or (44), respectively, as the sole isolable products (equation 25). Another striking feature of the reaction is the high chemospecificity. The condensation of the enol silyl ether (45), derived from p-acetoxyaceto-phenone, occurs in a chemospecific fashion with cyclododecanone oxime mesylate, the acetoxy moiety remaining intact (equation 26). Oxime sulfonates of aromatic ketones and cyclopentanones are not employable since complex reaction mixtures are formed. 

Alkylation/aldol reaction. Activated dibromides such as 2,2-dibromoalkanoic amides and a 1,3-dihalopropene incorporate R from RjMnLi and apparently generate new organomanganese species which can react with aldehydes. On the other hand, BUjMnLi can remove the functional group of a-acetoxy and a-(t-butyldimethylsiloxy) ketones and the resulting enolates react with aldehydes in a. n-selective manner. ... 

The experimental results and the known facility of O-desilylation of silyl enol ethers, such as 3-acetoxy-2-trimethylsiloxypropenes, under the given reaction conditions led Trost ° to suggest the intermediacy of an oxatrimethylenemethanepalladium complex 4 addition to the alkene at the less-substituted terminal carbon atom of 4 followed by tautomerism and ring closure would give rise to the cyclopropane. Since the palladium complex that is prepared from tris(dibenzylideneacetone)palladium(0)-chloroform complex [Pd2(dba)j CHClj] and triphen-ylphosphane also catalyzes the Brook rearrangement of an a-silyl ketone to a silyl enol ether, (2-oxo-3-silylpropyl) acetates can also serve as precursors of intermediate palladium complexes 4, and the same cyclopropanation reactions as with 3-acetoxy-2-trimethylsiloxypropenes can be carried out. 

Although the enolate of ketone (179) may be prepared and O-alkylated, the ketone itself is not reported to enolize in solution <77X2i5i>. Acetoxy-1,4-dithiocin (176 R = Ac) is thermally unstable, decomposing when heated above 50 °C with extrusion of sulfur. By analogy with related studies of other 1,4-diheterocins and with the failure of attempts to prepare the parent 1,4-dithiocin via the valence tautomerization of benzene disulfides <74AG818>, it is proposed that this thermal decomposition occurs via thermal valence tautomerization in the reverse direction, followed by sulfur extrusion from the so-formed arene disulfide (Scheme 58) <78X363i>. 

An a-acetoxy-epoxide is readily prepared from the corresponding ketone by peracid treatment of the enol acetate. The acetoxy-epoxide reacts with a cuprate reagent in the manner shown in Scheme 37, resulting in overall a-alkylation of the ketone. Unfortunately, the product yield varies widely, depending on the nature of the organocuprate reagent and the structure of the acetoxy-epoxide. ... 

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