Additions 1,4-benzoquinone, palladium acetate

Alkenes can also be oxidized with metallic acetates such as lead tetraacetate or thallium(III) acetate " to give bis-acetates of glycols. Oxidizing agents such as benzoquinone, Mn02, or 02, along with palladium acetate, have been used to convert conjugated dienes to l,4-diacetoxy-2-alkenes (1,4 addition). ... 

A number of intramolecular Pd-catalyzed 1,4-oxidations of conjugated dienes were developed.f In these reactions, two nucleophiles are added across the diene, one of which adds intramolecularly. So far, only heteroatom nucleophiles have been employed. In order to extend these intramolecular 1,4-oxidations to carbon nucleophiles, it was found that a vinylpalladium species can be obtained in situ from an alkyne via a chloropalladation. The approach is particularly attractive since it involves a Pd(II) chloride salt and could be compatible with the rest of the catalytic cycle. Reaction of dienyne with LiCl, and benzoquinone in the presence of palladium acetate as the catalyst, afforded the carbocyclization products. The reaction resulted in an overall stereoselective fltiri-addition of carbon and chlorine across the diene t B (Scheme 23). 

The use of a nitrogen nucleophile in the side chain (as an amide) also leads to an intramolecular 1,4-addition under the standard conditions for the palladium-catalyzed 1,4-oxidation reactions52. Nitrogen nucleophiles employed for this reaction comprise tosy-lamides, carboxamides, carbamates and ureas. The reactions are run in acetone-acetic acid with p-benzoquinone (BQ) as the oxidant. In most cases highly stereo- and regioselective reactions were obtained and some examples are given in Table 3. 

Addition of 7-amino-2,2-dimethylchromene 107 to 2-methyl-1,4-benzoquinone 108 in acetic acid/water leads to the 2-arylamino-5-methyl-1,4-benzoquinone 109 in moderate yield (Scheme 34). Oxidative cyclization of compound 109 using a stoichiometric amount of palladium(II) acetate in acetic acid under reflux provides pyrayaquinone A 110 [42,132]. 

One of the carbazole-l,4-quinones, 3-methoxy-2-methylcarbazole-l,4-quinone (941), required for the total synthesis of carbazomycin G (269), was already used as a key intermediate for the total synthesis of carbazoquinocin C, and was obtained by the addition of aniline (839) to 2-methoxy-3-methyl-l,4-benzoquinone (939), followed by oxidative cyclization with catalytic amounts of palladium(II) acetate (545,645) (see Schemes 5.124 and 5.125). Similarly, in a two-pot operation, 4-meth-oxyaniline (984) was transformed to 3,6-dimethoxy-2-methylcarbazole-l,4-quinone... 

Addition of the appropriate arylamines to 2-methyl-l,4-benzoquinone provides the desired 2-arylamino-5-methyl-l,4-benzoquinones as major products (ratios 2.3-2.9 1). Oxidative cydization of these intermediates leads directly to murraya-quinone A (51 % overall yield), koeniginequinone A (46 % overall yield) and koeniginequinone B (47 % overall yield). Using copper(II) acetate under the optimized reaction conditions described above (Table 15.2), these transformations have also been carried out vith catalytic amounts of palladium(II). 

Diacetoxylation of 1,3-dienes.1 Palladium-catalyzed oxidation of 1,3-cyclo-hexadiene with benzoquinone (used in catalytic amounts with Mn02 as the external oxidant) in acetic acid gives a 1 1 mixture of cis- and trans-, 4-diacetoxy-2-cyclohexene. Addition of LiCl or LiOAc has a profound effect on the stereochemistry. Oxidation in the presence of lithium acetate results in selective fraws-diacetoxylation, whereas addition of lithium chloride results in selective cw-diacetoxylation (equation I).2... 

The reaction conditions are similar to those employed in the diacetoxylation reaction, with the difference that the halide concentration (usually CI ) has been increased. Thus, palladium-catalyzed oxidation of 1,3-dienes with / -benzoquinone in the presence of lithium chloride and lithium acetate gives l-acetoxy-4-chloroalk-2-enes [78]. For example cyclohexa-1,3-diene and cyclohepta-1,3-diene afforded the corresponding chloroacetates 58a and 58b in good yield and >98% cis selectivity [Eq.(41)]. Cycloocta-1,3-diene gave a 61% yield of acetoxychlorination product (>98% cis), but in this case a 3 1 mixture of 1,4-and 1,2-addition products was formed. A number of substituted cyclic conjugated dienes work well, and, in all cases tried, the reaction proceeds with >97-98% cis selectively [52,78-81]. 

Palladium-catalyzed reaction of dienol 80 in acetone in the presence of acetic acid and benzoquinone resulted in an intramolecular 1,4-oxyacetoxylation (Scheme 8-28) [107], The stereochemistry of the reaction can be controlled via a slight variation of the ligand environment. Thus, under chloride-ion-free conditions, a rrawj-oxyacetoxylation occurs. Usually this reaction is highly stereoselective (>98% tram addition), except m = n = 2 in Scheme 8-28, where the tramlcis ratio is 75 25. When the reaction is run in the presence of a catalytic amount of chloride, the stereochemistry is reversed and now a 1,4-cts-oxyacetoxylation takes place. The effect of the chloride is the same as discussed above, i.e., it blocks the coordination of acetate so that cis migration by acetate cannot occur. 

A variety of arenes and heteroarenes react with alkenes in the presence of palladium(II) derivatives to produce alkenyl substitution products. Three methods are commonly employed for the in situ preparation of palladium derivatives (i) direct metallation of an arene or heteroarene with a Pd(II) salt (ii) exchange of the organic group from a main-group organometallic to a Pd(II) compound (iii) oxidative addition of an organic halide, an acetate, or triflate salt to Pd(0) or a Pd(0) complex. For catalytic reactions Cu(II) chloride or p-benzoquinone is usually used to reoxidize Pd(0) to Pd(II). 

Prior to the discovery of the aryl-Heck reaction (Chapter 72), the direct Pd-promoted oxidative cyclization of diaryl amines to carbazoles was well known. In 1975 Akennark reported this reaction (Scheme 1, eqnation 1) [1], In addition, A -phenylanthranUic acid gave carbazole-l-carboxylic acid (60%). Miller and Moock used Pd(OAc)j to cyclize 6-anilino-5,8-dimethylisoquinoIine to eUipticine in low yield [2]. The second advance in this chemistry was reported independently by Bittner [3] and Furukawa [4], who described the Pd-mediated (stoichiometric) oxidative conversion of 2-anilino-l,4-benzoquinones and 2-anilino-l,4-naphthoquinones to the corresponding carbazole-l,4-diones and benzo[ ]carbazole-l,6-diones (equations 2, 3). Furukawa s studies included syntheses of several carbazolequinone alkaloids. In 1995 Akermark and colleagues developed catalytic versions (i.e., using tert-butyl hydrogen peroxide [TBHP] or oxygen) of this cyclization (equation 3) [5,6], which elevated the importance of this palladium oxidative cyclization, mainly because of the expense of Pd(OAc)2. Somewhat earlier, Knbiker used cupric acetate as a reoxidant in a synthesis of carbazole-l,4-quinones [7]. 

Backvall has devised a catalytic method for the conversion of 1,3-dienes into their 1,4-diacetoxy-derivatives. Less than 3% 1,2-addition occurs. The reaction is carried out in acetic acid using manganese(IV) oxide, together with a small quantity of benzoquinone, as oxidizing agent. The catalyst is palladium(II) acetate in the presence of lithium acetate. Under these conditions, 1,3-cyclohexadiene affords irflns-l,4-diacetoxycyclohexene (path (b)). If a little lithium chloride is also added, coordination of the acetate ion to palladium is blocked by chloride, the better of the two ligands. This suppresses the cis-migration pathway (b) so that cis-1,4-diacetoxycyclohexene (path (a)) now becomes essentially the only product. If the concentration of lithium chloride is increased still further, chloride replaces acetate as the second nucleophile. 

Non-conjugated dienes ate the source of many palladium enyl complexes. Nucleophilic attack at one of the double bonds of the coordinated diene has been used most, and many examples can be found in COMC (1982) and COMC (1995). The external attack of the nucleophile leads to an overall /rtf r-addition of Pd and the incoming species to the double bond. Oxidation followed by nucleophilic attack on COD affords <7,7 -enyl derivatives from Pd(l,5-COD)(benzoquinone). In the presence of acid, benzoquinone oxidizes Pd(0) to a Pd(n) diene complex with the concomitant formation of hydroquinone. If a suitable nucleophile is present, such as OAc when acetic acid is used, attack on the diene takes place, and a palladium complex is formed (Scheme 80). A weaker nucleophile like CH3S03 is not capable of adding to the double bond, and the reaction stops at the COD Pd(n) complex. The behavior of other quinones and acids was also studied. ... 

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