1.4- diacyloxylation

In the 1,4-diacyloxylation, two carboxylate anions are added in a 1,4 manner to a conjugated diene in an oxidative process involving the removal of two electrons. The catalyst employed is a palladium(II) salt, usually Pd(OAc)2- The 1,4-diacyloxylation may be an intermolecular or an intramolecular process. In the latter case the result is a lactonization. In most cases the stereochemistry of the 1,4-addition of the two carboxylates to the 1,3-diene can be controlled to give either a 1,4-cis or l,4-tra s adduct. 

One example of such a reaction was reported in 1971 by Brown and Davidson [55], who studied oxidation reactions of 1,3- and 1,4-cyclohexadiene. These authors observed that reaction of 1,3-cyclohexadiene with p-BQ in acetic acid in the presence of catalytic amounts of Pd(OAc)2 produced l,4-diacetoxy-2-cyclohexene of unknown configuration. At the time. Brown and Davidson were uncertain about the mechanism, and suggested possible involvement of radicals. A related palladium-catalyzed 1,4-diacetoxylation of butadiene employing as an oxidant and a heterogeneous Pd-Te catalyst has been developed and commercialized by Mitsubishi Chemicals [56]. 

The crucial Hgand which dramatically changes the stereochemical outcome of the reaction is Cl. Thus, in the absence of chloride ligands, a l,4-tra7is-diacetoxylation occurs, whereas in the presence of a catalytic amount of chloride ions a 1,4-ds-diacetoxylation takes place. An explanation of these results is that, in the absence of chloride ions, the counterion to palladium is acetate, which can migrate from the metal to carbon. Addition of lithium chloride, even in catalytic amounts, results in displacement of the acetate on palladium by chloride due to the very strong 

Although acyclic dienes in general gave lower yields than the cyclic ones, the 1,4-stereocontrol obtained for internal conjugated dienes is of synthetic interest. For example, (E,E)- and (F,Z)-2,4-hexadiene was stereoselectively transformed to the d,l- and meso-l,4-diacetate, respectively (see later discussion). 

4-acetoxytrifluoroacetoxylation of 1,3-dienes was achieved in the presence of trifluoroacetic acid and lithium trifluoroacetate [66]. For cyclic dienes the relative yield of unsymmetrical 1,4-addition product is high (94-95% or better). For example, palladium-catalyzed oxidation of 1,3-cyclohexadiene under these 

In intermolecular 1,4-diacyloxylation, two carboxylate anions react with the diene in the presence of a palladium(II) catalyst and an oxidant according to Eq.(33). 

In one procedure, as mentioned above, Mn02 was employed as the oxidant to reoxidize the hydroquinone to benzoquinone. In another study it was demonstrated that the hydroquinone can be recycled electrochemically by anodic oxidation [61]. The reaction is performed in acetic acid with LiC104 as electrolyte with catalytic amounts of both Pd(OAc)2 and p-benzoquinone in a membrane-separated cell. 

---

The 1,4-diacetoxylation was also extended to the use of other acyl groups than acetyl. Thus, an unsymmetrical 1,4-acetoxy-trifluoroacetoxylation of 1,3-dienes was developed by the use of added trifluoroacetic acid to the acetic acid used as the solvent330. With the use of acetone as the solvent with an added carboxylic acid a general diacyloxylation was obtained and, for example, the 1,4-dibenzoates of 2-cycloalkene-l,4-diols were prepared directly from the corresponding l,3-cycloalkadienes33d. 

The allylic oxidation of 1,3-dienes catalyzed by Pd(II) complexes in the presence of BQ (added in stoichiometric quantities or used catalytically with a stoichiometric amount of a co-oxidant) leads to the formation of 1,4-oxidation products under mild reaction conditions (at room temperature in AcOH) [42], A very interesting stereochemical aspect arises in 1,4-diacyloxylation reactions of cycloalkenes when carboxylate salts are used as nucleophiles. Although the relative stereochemistry... 

The catalytic cycle of the palladium-catalyzed diacyloxylation follows the cycle depicted in Scheme 8-6 (X = RCOO, Y = R COO ). The coordination of a quinone in the Ji-allyl)palladium intermediate was demonstrated by NMR studies including T, measurements [58]. Attack by the second nucleophile results in the formation of the 1,4-addition product and a palladium(0)-benzoquinone complex. In an independent mechanistic study, it was shown that such Pd(0)-benzoquinone complexes, which are stable at neutral conditions (pH 7), react with weak acids to give hydroquinone and the palladium(II) salt of the acid [Eq.(36)] [59],... 

The use of dienecarboxylic acids (cf. Section 8.3.1.1, under Intramolecular 1,4-diacyloxylation ) under the conditions for haloacyloxylation in acetone resulted in a highly stereoselective chlorolactonization [Eqs.(44) and (45)] [67]. The reaction proceeds >98% as a 1,4-c/5 addition and involves the same intermediate lactone jr-allyl complex as in the intramolecular diacyloxylation. 

Interestingly, this 1,4-carbochlorination occurs syn, which constrasts with that via the vinylpalladation in Eq.(49), which occurs anti. An explanation for this difference is that the allylsilane attacks the palladium-diene complex anti, leading to a rrans-carbopalladation of the double bond. This is the first example of nucleophilic attack by an allylsilane on an olefin coordinated to a metal. Direct evidence for a frans-carbopalladation was provided by the isolation of the proposed 7r-allyl intermediate of Eq.(51) as its chlorodimer 98a from reaction of 97 with Li2PdCl4 in the absence of benzoquinone [Eq.(52)] [119b]. The trans relationship between palladium and the carbon that has attacked the diene was established by the reporter ligand technique used for 41 in Section 8.3.1.1 under Intramolecular 1,4-diacyloxylation . 

In this reaction two carboxylate anions are added in a 1,4-fashion to a conjugated diene in an oxidation process involving removal of two electrons. The catalyst employed is a palladium(II) salt, usually Pd(OAc)2. The 1,4-diacyloxylation may be an intermolecular or... 

The use of p-BQ in catalytic amounts (as mentioned earlier), along with a stoichiometric oxidant, makes the 1,4-diacyloxylation more synthetically useful. The principle of the reaction is shown in Scheme 11.13. 

Intramolecular 1,4-Diacyloxylation An intramolecular variant of the palladiumutilizing dienes with a carboxyl group in the side chain (Scheme 11.16) [75, 76]. Also in this case the stereochemistry of the 1,4-addition can be controlled by variation of the ligand environment. Thus, in the absence of chloride a trans acetoxylactonization takes place, whereas in the presence of a catalytic amount of chloride a cis acetoxylactonization occurs. The catalytic intermediate was isolated and stereochemically assigned as its bipyridyl complex 49 [76]. In the stereochemical assignment, bipyridyl was utihzed... 

A palladium-catalyzed intramolecular lactonization was used as a key step in the enantioselective synthesis of paeonilactones A and B (Scheme 11.38) [127]. Intramolecular 1,4-diacyloxylation of the cyclohexadienylacetic add 101 afforded 102, which was hydrolyzed to 103 this in turn was transformed to 104 in a Mitsunobu reaction. Hydrolysis of 104 to 105 and stereoseledive alkylation afforded 106, which was converted to paeonilactone A. 

---