A-Acetoxylation

However, this does not explain the structural requirements for the oxygen function vicinal to the nitrite ester a-ketones, ketals and hydroxyls are cleaved, but a-acetoxyls are not. 

Esters and acetylated hydroxyl groups are completely stable under the experimental conditions, but with ketals 10 29,110,112 yields are generally observed in the thermal reaction. Double bonds do not seem to interfere seriously with the course of the reaction provided that the geometric relationship of the free hydroxyl group to the angular methyl group is not changed drastically. In some cases allylic acetoxylation occurs, e.g., at C-7 of A -steroids. ° Ketones are usually stable (especially under photo-lytic conditions) but occasionally a-acetoxylation has been observed. 

Clearly a two-equivalent oxidation of the enol is taking place. Product work has been summarised by Criegee and in general a-acetoxylation occurs. 

Then the synthetic 32 was converted to the cyanoglucoside sutherlandin (44) which was isolated from leaves of Acacia sutherlandii. Acetylation of a diastereomeric mixture of 32 gave the corresponding acetate which was subjected to the hydrogenation and the subsequent oxidation to yield the a-acetoxyl ketone (45, 84% overall yield from the acetate of 32). The Homer-Emmons reaction of 45 using diethyl cyanomethylphosphonate furnished (Z)-46a (33% yield from 45) and ( )-46b (31% yield from 45). Deprotection of the presumably desired (Z)-46a afforded (Z)-44 (76% yield), whose C-NMR spectra were identical with those of the natural sutherlandin (44) (Fig. 6). 

Compound 264 is unexpectedly stable against light, but can easily be oxidized to the sulfoxide 265 and the sulfone 266. Sulfoxide 265 can be isolated and a-activated by reaction with acetic anhydride (Scheme 4.46). a-Acetoxylated tetrahydrothio-phene 267 has 0,S-acetal-like reactivity and can be functionalized with various alcohols or thiols under acid catalysis with camphorsulfonic acid (CSA) (268). 

Asymmetric acetoxylation of esters.3 Reaction of lead tetraacetate with the silyl enolate of the chiral ester 2 derived from camphorsulfonic acid results in a-acetoxylation with high diastereoselectivity. After crystallization 3 is obtained in 95% de. The product can be hydrolyzed to the optically active a-acetoxy carboxylic acid by K2C03 or reduced to the chiral glycol 4 by LiAlHj. 

Addition of an organocuprate to the chiral ester (5) followed by similar a-acetoxylation results in generation of two contiguous asymmetric centers to give 7 with high optical purity. 

Ketosulfoxides, which are intermediates in the alkylation of ester by Li-CH2 SOCH3, are cleaved to ketones (Eq. (234) ) 5 21K Analogously, the acetoxy group has been reductively removed from a-acetoxylated nitriles 522 ... 

Acetophenones, aliphatic and cyclic ketones were a-acetoxylated by DIB in acetic acid-acetic anhydride, in the presence of sulphuric acid, in moderate yield some / -diketones were similarly acetoxylated at the methylene carbon. The more reactive trimethylsilyl ethers reacted at room temperature without acid catalysis, with retention of their silyl group the products came either from substitution of the vinylic hydrogen or from bis acetoxylation of the double bond. 

Table 19 shows results from the a-acetoxylation of two 2-alkyl-indans under different conditions analogous homogeneous reactions are included for comparison. Table 19 demonstrates that, at most, a weak effect is noticeable in the case of 2-t-butylindan, in that anodic oxidation on platinum, a strongly adsorbing metal, gives a cis/trans ratio that is about 10 times that observed from a 2-t-butyl-1-indanyl cation generated by solvolysis. Ratios on the weaker adsorbing electrode materials, carbon and lead dioxide, fall in between. For a smaller substituent (R = methyl) no effect is observable. 

Numerous examples are available that demonstrate the utility of the process. Sasaki and Eguchi utilized LTA to effect a-acetoxylation of isodihydro-0 acetylisophotosantonic lactone (1). This oxidation is both chemoselective towards the ketone and regioselective towards the less substituted position... 

Reacticm of ketcmes with LTA in benzene in the presence of boron trifluoride etherate at or below room temperature effects rapid a-acetoxylation." The yields are indeed improved in most cases, for... 

Other transition metal salts mediate in similar oxidations. For example, mercury(II) acetate, a milder reagent than LTA, effects a-acetoxylation through a comparable mechanism. However the corresponding yields for these processes are poor. 3,3-Dimethylcyclohexanone, for example, is oxidized to the a-acetoxy derivative in only 14% yield.The, 7-unsaturated ketone, isopugelone, exhibits no oxidation at the a- or a -positions, but affords a product derived from isomerization of the alkene and allylic oxidation. Not surprisingly therefore the reagent has found little synthetic application for this transformation. 

Preformed enolates are susceptible to further methods of oxygenation. For example treatment with LTA in benzene effects a-acetoxylation at lower temperature and more rapidly than the corresponding enol examples. Similarly a-benzoylation using benzoyl peroxide is possible for both lactones and 3-keto esters and presumably could be used for less-activated ketones. 

Lead(IV) salts will a-oxygenate enol ethers as they do enols vide supra), although in this case the process involves bisoxygenation of the unsaturated Ullage and subsequent hydrolysis. For example, the combination of lead tetrabenzoate and triethylammonium fluoride at 0-25 C effects efficient a-benzoyl-oxylation, e.g. (68) to (69). 0, y-Unsaturated ketones are also successfully oxidized, e.g. (70) to (71). The correspon ng LTA a-acetoxylations are possible, but the benzoate salt remains the transition metal reagent of choice for these substrates.These reactions appear to be uniformly efficient and perluq)S deserve wider synthetic tq>plication. 

Enamines are readily available ketone derivatives." Exposure of these compounds to certain transition metal salts has been shown to produce a-oxygenated imines which are rapidly hydrolyzed to their ketone counterparts. Thus, for example, morpholino enamines, prepared in situ, are a-acetoxylated on treatment with thallium triacetate. The process is thought to involve either direct nucleophilic extraction of an acetate unit or the intermediacy of an organothallium species which subsequendy undergoes anchimerically assisted intramolecular acetoxy migration to generate the a-acetoxyimine (Scheme IS). 

These various intermolecular a-acetoxylation reactions have intramolecular counterparts. For example, treatment of the sulfinylbutanoic acid shown in equation (11) with acetic anhydride containing p-toluenesulfonic acid yields a sulfenylated butanolide, the carboxylic acid function having intercepted the a-thiocarbocation intermediate. Yet another demonstration of Ae intramolecular process, due to Al-lenmark, is the cyclization of o-carboxyphenyl benzyl sulfoxide with acetic anhydride to form the 1,3-benzoxathian-4-one shown in equation (12). This reaction was also conducted with one of the... 

A combination of the Pummerer rearrangement and the Ritter reaction occurs in the reaction of acetonitrile with methyl phenyl sulfoxide (equation 25) in a mixture of irifluoroacetic acid and its anhydride, although a substantial amount of the nonnal a-acetoxylation also occurs. Participation by amido groups is also possible, the interest here being largely in the construction of lactams via the intramolecular cycli-zation mode. Whereas Wolfe and his coworkers were unable to find conditions for the cyclization of S-phenylcysteinamide sulfoxides under Pummerer conditions, Kaneko found that variously substituted... 

The anodic a-acetoxylation or a-methoxylation of ketones has been shown to be a powerful tool for the 1,2-transposition of the caibonyl group. The overall process is described by equation (24). ... 

The reaction mechanism of the a-methoxylation or a-acetoxylation of amides and carbamates" has been shown to involve direct one-electron removal from the lone pair electrons of the nitrogen atom in the initial step when inert supporting electrolytes are used. 

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