Palladium mediated oxidation

The same group reported a palladium-mediated oxidation of methane to a methanol derivative employing a CuCl2 and Pd/C-based catalyst system and dioxygen in a trifluoroacetic acid/water mixture.18 A system was also described, which mediated the oxidation of ethane (Equation (10)). 

Several examples have been reported of the use of palladium-mediated oxidation reactions of alcohols and alkyl halides. Palladium(II) acetate in the presence of iodobenzene converts primary and secondary alcohols into carbonyl compounds under solid-liquid two-phase conditions [20], However, other than there being no further oxidation to carboxylic acids, the procedure has little to commend it over other methods. It is relatively slow with reaction times in the order of 2 days needed to achieve yields of 55-100%. 

Hill et al. reported an efficient short synthesis of staurosporinone (293) using a palladium-mediated oxidative cyclization of the bisindolylmaleimide arcyriarubin A (349) as the key step (766). The key intermediate, arcyriarubin A (349), was prepared... 

Ohkubo et al. reported the synthesis of the arcyriaflavins B (346), C (347), and D (348) involving a base-induced indolylation of dibromo-Af-methylmaleimide 1420 and a palladium-mediated oxidative cyclization of the bisindolylmaleimides 1428, 1429, and 1430 as key steps (337). The reaction of 6-benzyloxyindole (1419) and... 

Scheme 1. Palladium-mediated oxidative coupling reactions of olefins and water.

In a palladium-mediated oxidative coupling reaction, alkenes such as methyl acrylate, acrylonitrile, or styrenes cyclize with 6- [(diinethylainino)methylene]amino -l,3-dimethyluracil to give the corresponding 6-substituted pyrido[2,3-[Pg.128]

Palladium-mediated oxidative arylation of thiophene has also been reported <8SJ0CS272>. Thus, treatment of 2-formylthiophene with palladium acetate in a mixture of acetic add and benzene gave 2-formyl-4-phenylthiophene (30%), 2-formyl-5-phenylthiophene (5%) and 5,5 -diformyl-2,2 -bithienyl (16%). It has been suggested that preliminary palladation of benzene would lead to 4-phenylation of the thiophene, while palladation of the thiophene would produce the 5-phenylated product. 

In 1980 Fujiwara and colleagues described for the first time a palladium-mediated oxidative carbonylation of arenes to benzoic acids [9—11]. The direct carboxylations of benzene, toluene, anisole, chlorobenzene, furan, and thiophene were carried out under CO and in the presence of Pd(OAc)2- 2-43 % of the corresponding benzoic acids were formed as the terminal products. Later on, the reaction was performed with a catalytic amount of palladium salts using tert-... 

Scheme 8.15 Palladium-mediated oxidative carbonylation of alkynes...

Scheme 8.30 Palladium-mediated oxidative carbonylation towards lactones...

The first metal-mediated synthetic approach to coumestans was described by Kappe and Schmidt in the early 1970s, when they were able to prepare the disubstituted coumestans 71 through a palladium-mediated oxidative cyclization of the 4-hydroxy-2-phenyl-coumarins 70 (Scheme 30) [123]. The process involves the initial oxidative addition of the OH imit of 70 to Pd(0), followed by orf/zo-metalation of the neighboring phenyl ring, and final reductive elimination. 

The intramolecular Heck reaction presented in Scheme 8 is also interesting and worthy of comment. Rawal s potentially general strategy for the stereocontrolled synthesis of the Strychnos alkaloids is predicated on the palladium-mediated intramolecular Heck reaction. In a concise synthesis of ( )-dehydrotubifoline [( )-40],22 Rawal et al. accomplished the conversion of compound 36 to the natural product under the conditions of Jeffery.23 In this ring-forming reaction, the a-alkenylpalladium(n) complex formed in the initial oxidative addition step engages the proximate cyclohexene double bond in a Heck cyclization, affording enamine 39 after syn /2-hydride elimination. The latter substance is a participant in a tautomeric equilibrium with imine ( )-40, which happens to be shifted substantially in favor of ( )-40. 

Another compound 9 with three heterocyclic rings linearly fused (5 5 5) with two heteroatoms has been prepared from 1,1 -carbonyl diindole 297 <2001T5199>. Palladium-mediated coupling of the 2- and 2 -positions of 297 afforded the 1,1 -carbonyl-2,2 -biindolyl 9. 1,1 -Carbonyl diindole 297 was in turn obtained in 41% yield from 1,1 -carbonyldiimidazole 296 by reaction with indole in DMSO at 125 °C. The palladium-catalyzed coupling step afforded the desired product 9 in low yield and required a stoichiometric amount of palladium acetate. Therefore, it was felt prohibitively expensive. Addition of various co-oxidants (Ac20, Mn02, and Cu(OAc)2, etc) to make the reaction catalytic in palladium did not result in any improvement of the yield of 18 (Scheme 53). 

In a stoichiometric reaction the 6jr-allyl)palladium complex 66 was isolated and characterized5815. In a subsequent reaction the jr-allyl complex was reacted with benzoquinone in acetic acid to give an allylic acetate, which was hydrolyzed and oxidized to theaspirone. Interestingly, a quite high diastereoselectivity for the turns methyl isomer was obtained in the palladium-mediated spirocyclization (equation 28). 

Hydroboration and oxidation of 160 yields an alcohol that is subsequently oxidized with PDC to give ketone compound 161. Enolization and triflation converts this compound to enol triflate 162, which can be further converted to x,/i-unsaturated ester 163 upon palladium-mediated carbonylation methox-ylation. The desired alcohol 164 can then be readily prepared from 163 via DIBAL reduction. Scheme 7 50 shows these conversions. 

A molybdenum-mediated oxidative coupling of aniline 1 with cyclohexene 2a provides carbazole 3. Alternatively, the same overall transformation of aniline 1 to carbazole 3 is achieved by iron-mediated oxidative coupling with cyclo-hexa-1,3-diene 2b or by palladium-catalyzed oxidative coupling with arenes 2c. The use of appropriately substituted anilines and unsaturated six-membered hydrocarbons opens up the way to highly convergent organometallic syntheses of carbazole alkaloids. 

The formation of carbon-carbon bonds by palladium-promoted reactions has been widely used in organic synthesis [114-116]. A major advantage is that most of these coupling reactions can be performed with catalytic amounts of palladium. Palladium(II)-catalyzed reactions, e.g., the Wacker process, are distinguished from palladium(O)-catalyzed reactions, e.g., the Heck reaction, since they require oxidative regeneration of the catalytically active palladium(II) species in a separate step [117]. Several groups have applied palladium-mediated and -catalyzed coupling reactions to the construction of the carbazole framework. 

The oxidative cyclization of Ar,Ar-diarylamines to carbazoles has been achieved by thermal or photolytic induction [7, 75]. However, the yields for this transformation are mostly moderate. Better results are obtained by the palladium(II)-mediated oxidative cyclization of Ar,Ar-diarylamines (Scheme 27). Oxidative cyclization by heating of the Ar,Ar-diarylamines 76 in the presence of a stoichiometric amount of palladium(II) acetate in acetic acid under reflux provides the corresponding 3-substituted carbazoles 77 in 70-80% yield [118]. The cou-... 

Scheme 27 Palladium(II)-mediated oxidative cyclization ofiSr,iST-diarylamines...

The palladium(II)-mediated oxidative cyclization of Ar,AT-diarylamines is useful for convergent total syntheses of a range of structurally different carbazole alkaloids. Goldberg coupling of 2,3-dimethoxyacetanilide 80 and 2-bromo-5-methylanisole 81 and subsequent alkaline hydrolysis affords the diarylamine 82... 

The Goldberg coupling between 5-acetylamino-2,2-dimethylchromene 84 and 5-bromo-2-methylanisole 85 followed by hydrolysis leads to the diarylamine 86, which on palladium(II)-mediated oxidative cyclization affords pyrayafoline A 87 [ 17] (Scheme 30). Starting from 7-acetylamino-2,2-dimethylchromene, the method has been applied to the synthesis of 0-methylpyrayafoline B [54]. 

The palladium(II)-mediated oxidative cyclization is also applied to the synthesis of carbazole-l,4-quinone alkaloids. The required arylamino-l,4-benzo-quinones are readily prepared by arylamine addition to the 1,4-benzoquinone and in situ reoxidation of the resulting hydroquinone [131]. 

An even more direct approach to carbazole-3,4-quinone alkaloids is provided by the palladium(II)-mediated oxidative coupling of ort/zo-quinones with ary-lamines, which gives access to this class of natural products in a three-step route [137]. 

Ether cleavage of 4-heptyl-3-methylveratrole 121 using boron tribromide affords 4-heptyl-3-methylcatechol 122 (Scheme 38). Oxidation of the catechol 122 with o-chloranil to 4-heptyl-3-methyl-l,2-benzoquinone 123 and subsequent immediate addition of aniline leads to 5-anilino-4-heptyl-3-methyl-l,2-benzo-quinone 124. Unlike the very labile disubstituted ort/zo-quinone 123, compound 124 is stable and can be isolated. Palladium(II)-mediated oxidative cyclization of the anilino-l,2-benzoquinone 124 provides carbazoquinocin C 51. 

Menendez et al. reported the synthesis of murrayafoline A (7) by palladium(II)-mediated oxidative double C-H activation of a diarylamine assisted by microwave irradiation (585). The aniline derivative 598 was obtained by O-methylation of 5-methyl-2-nitrophenol (625) followed by catalytic hydrogenation. The required diarylamine 654 was obtained by N-arylation of the aniline derivative 598 with phenyllead triacetate (653) in the presence of copper(II) acetate. Under microwave-assisted conditions, in the presence of more than the stoichiometric amount of palladium(II) acetate and a trace of dimethylformamide, the diarylamine 654 was cyclodehydrogenated to murrayafoline A (7) (585) (Scheme 5.47). 

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