Acetoxylation Lead tetraacetate

ACETOXYLATION Lead tetraacetate. Selenium dioxide. Trimethyloxonium fluoroborate. 

A direct method for introduction of a C-21 acetoxyl group into a 20-keto-pregnane is by reaction with lead tetraacetate at room temperature. Although originally the reaction carried out in hot acetic acid gave low yields, a careful study by Henbest has defined conditions so that yields as high as 86 % can be obtained at room temperature. The preferred solvent is 5 % methanol in benzene, with boron trifluoride etherate as catalyst. With either methanol or benzene, the yield is less than 4%. 

Diosphenol (58) is easily prepared in 47 % yield from testosterone (60) by acetoxylation with lead tetraacetate followed by oxygenation in an alkaline medium. 

It has since transpired that the active aziridinating species in these reactions are the N-acetoxylated hydrazine derivatives, rather than nitrenes exposure of ethyl-quinazolinone ( Q1-NH2 ) to lead tetraacetate at low temperature generates N-(acetoxyamino)-quinazolinone ( Q -NHOAc ), which is a relatively stable sub-... 

Acetoxylation at an allylic position is the typical reaction of lead tetraacetate but no kinetic data are available. Product studies favour a heterolytic mecha-nism . 

Oxidation of oxyberberine (58) with lead tetraacetate effected 13-acetoxyl-ation to give 13-acetoxyoxyberberine (116), which was further oxidized to the 14-alkoxy-8,13-dioxo compounds 117 and 118 (Scheme 25). Reduction of 116 with lithium aluminum hydride followed by sodium borohydride afforded ( )-ophiocarpine (92) (78). 

The natural diterpenoid rostratone 16 is synthesized from ethylene ketal as shown in Scheme 17.162 In this synthesis, the Pd-mediated remote acetoxylation is achieved by G-H bond activation by Na2PdCl4 giving palladacycle dimers followed by treatment with pyridine and lead tetraacetate. 

Many of the early reports of spin-trapping experiments were focused on mechanistic investigations, and some of these feature in the early reviews (see p. 4). Unfortunately, it is in this application that inferences drawn may be most suspect. For example, the inability of the method to differentiate between radical trapping on the one hand, and a combination of nucleophile trapping with one-electron oxidation on the other, is a serious shortcoming. An early example of this was the tentative conclusion that acetoxyl radicals were spin-trapped by PBN competitively with their decarboxylation in reactions of lead tetraacetate. In view of the rapidity of the decarboxylation reaction, trapping of acetate ion and subsequent oxidation seems a likely alternative. 

According to Ando et al. (2000), the sonolytic acetoxylation of styrene by lead tetraacetate follows the ion-radical mechanism. Lead tetraacetate was not subject to the sonication influence. The ultrasonic effect facilitates electron transfer from styrene (the nonmetallic donor) to lead tetraacetate. 

Recently, a clean formation of 2,3-dihydro-l,4-dioxane 10 has been described in a two-step process starting from 1,4-dioxane. This approach takes advantage of the capability of lead tetraacetate to engage in the acetoxylation of C-H bonds adjacent to ethereal oxygen centers (Scheme 25) <20050S99>. 

An unactivated methyl group can be functionalized by the cyclopalladation of oximes. The equatorial methyl of geminal methyls in steroids or hexapyr-anosides is selectively acetoxylated by the reaction of the palladation complex 523 of the 3-oxime with lead tetraacetate[467,468]. 

Oxidation with lead tetraacetate is a far less selective process.490,491 Studied mainly in the oxidation of cycloalkenes, it gives stereoisomeric 1,2-diol diacetates, but side reactions (allylic acetoxylation, skeletal rearrangement) often occur. A change in reaction conditions in the oxidation of cyclopentadiene allows the synthesis of different isomeric mono- and diesters.492... 

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. 

Acetoxylation (see also Acyloxylation) Lead tetraacetate, 62, 155 Acylation (see also Benzoylation, Formy-lation)... 

These and related reactions of lead tetraacetate have been widely used in synthetic organic chemistry, and are the subject of several reviews.6-10 However, they have found relatively few applications in the carbohydrate field specifically. One important application has been the synthesis of ketones by way of acetoxylation of suitable unsaturated compounds. By treating 1,2-0-isopropylidene-2-propene-l, 2-diol (I) in benzene at 50° with... 

Oxidative nucleophilic substitution is, however, a more versatile technique and a much better choice for target-oriented synthesis (Sections 15.1.1 and 15.1.2.2). In 1950, Wessely and co-workers examined the use of lead tetraacetate (LTA) in acetic acid to determine the structure of phenols and, in doing so, they developed their oxidative acetoxylation reaction, referred to herein as Wessely oxidation (Figure 13) [68-76]. If both an ortho- and a para-position are available to accommodate the entry of the acetoxy nucleophile, ortho products often predominate even when the ortho position is already occupied by a resident alkyl (e.g. 40 —> 41a/b) or allcoxy group (Figure 13) [69, 74]. 

Lead tetraacetate in glacial acetic acid is used for 2,5-acetoxylation of furan derivatives272 ... 

Favorski-type rearrangement Reaction of lead tetraacetate and BFj in benzene with the ketone (1) results in a mixture of a -acetoxylated ketones, 2a and 2b. If... 

Acetoxylation of enol thioethers. The reaction of enol thioethers with lead tetraacetate (1,1 equiv.) in THF for 1 hour followed by addition of BFj etherate (or 5 N KOH-ether) results in allylic acetoxylation. The reaction is considered to involve bisacetoxylation of the double bond. Oxidation of sulfur is not observed. Examples ... 

Lactams, by Beckmann rearrangement, 343 Lactols, 402 Lactones, 346-349, 397 Lanosterol, 401, 408 Lead tetraacetate, acetoxylation of enol derivatives, 184 —, acetoxylation of ketones, 176-177... 

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. 

The enol form of mesitylphenylacetaldehyde, a vinylic alcohol, when dissolved in acetic acid and treated with lead tetraacetate at 40 °C, gives 2-acetoxy-2-mesitylphenylacetaldehyde in 86% yield 1151. The result can be interpreted as the addition of acetoxyls across the enol double bond followed by elimination of one molecule of acetic acid (equation 275),... 

Esters of hydroxy ketones are prepared by acetoxylation with lead tetraacetate in benzene. Cyclohexanone furnishes a 75% yield of 2-ace-toxycyclohexanone and a 3% yield of cis-2,6-diacetoxycyclohexanone after heating at 80 C for 8 h [438], Similarly, 3a-hydroxy-5p-pregnan-20-one yields 64% of 21-acetoxy-3a-hydroxy-5 -pregnan-20-one [439] after 4 h at room temperature. 

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