Coupling palladium-catalyzed

Palladium-catalyzed coupling reactions of organic halides with olefins or dienes (R. F. Heck, 1979) are broad in scope and simple to carry out. Anhydrous conditions or any special technique are not required and most functional groups are tolerated. 

The Boekelheide reaction has been applied to the synthesis of non-natural products with the preparation of quaterpyridines serving as an example. The sequence began with the 2,4-linked bipyridyl-N-oxide 25. Execution under the typical reaction conditions produced the expected bis-pyridone 26. Treatment with POCI3 afforded the corresponding dichloride that was submitted to a palladium-catalyzed coupling with 2-stannyl pyridine to produce the desired quaterpyridine 27. 

The parent system 4 has also been jnepared employing a double reductive ring closure of a dinitrodiphenylbenzene derivative (Scheme 25). The required starting material, 195, was prepared using a palladium-catalyzed coupling of 1,4-dibromo-2,5-dinittobenzene with phenylboronic acid and after reaction with tri-ethylphosphite in hot tert-butylbenzene, 4 could be isolated in a moderate yield (92JHC1237). 

The above procedure was used for the preparation of all compounds except 104p, which was obtained from 104r by palladium-catalyzed coupling with tributylvinyl-stannane followed by palladium-catalyzed cyclopropanation of the resulting vinyl intermediate with diazomethane (Scheme 32) (99BMC3187). 

Due to their successful synthesis of 2-(4 -chlorophenyl)-4-iodoquinoline from the corresponding precursor acetylene, Arcadi et al. (99T13233) developed a one-step synthesis of 2,4-disubstituted quinolines via palladium-catalyzed coupling reactions. An example is the Heck reaction of 4-iodoquinoline (131) with a-acetamidoacrylate (132). This one-pot synthesis yielded adduct 133 in 50% overall yield after purification via flash chromatography. 

AN IMPROVED SYNTHESIS OF BIARYL DERIVATIVES VIA THE PALLADIUM CATALYZED COUPLING OF ARYL BROMIDES... 

The synthesis of 1-alkenylboronic acids from l-alkenylmagnesiums or -lithiums suffers from difficulty in retaining the stereochemistry of 1-aikenyl halides, but the palladium-catalyzed coupling reaction of diboron 82 with 1-aikenyl halides or tri-flates directly provides 1-alkenylboronic esters (Scheme 1-43) [157, 158]. Although the reaction conditions applied to the aryl coupling resulted in the formation of an... 

The Heck coupling reaction appeared to be a route of choice to achieve the synthesis of the modified-DIOP ligands. We previously studied the palladium-catalyzed coupling of acrolein and acrolein acetals with several polyaromatic and heteroaromatic bromides either in the presence of homogeneous or heterogeneous catalytic systems (6, 7). After optimization of the reaction conditions, high conversions and selectivities were achieved except with anthracenyl derivatives (8). Based on these results, we developed the synthesis of the desired ligands. The... 

Table 21.1 Palladium-catalyzed coupling of aryl bromides with dioxolane...

Organozinc compounds are also useful in palladium-catalyzed coupling with aryl and alkenyl halides. Procedures for arylzinc,156 alkenylzinc,157 and alkylzinc158 reagents have been developed. The ferrocenyldiphosphine dppf has been found to be an especially good Pd ligand for these reactions.159... 

Scheme 8.12. Palladium-Catalyzed Coupling of Stannanes with Halides and Sulfonates... 

Alkyl substituents on boron in 9-BBN derivatives can be coupled with either vinyl or aryl halides through Pd catalysts.22413 This is an especially interesting reaction because of its ability to effect coupling of saturated alkyl groups. Palladium-catalyzed couplings of alkyl groups by most other methods often fail because of the tendency for (3-elimination... 

At the same time, Schmidtchen et al. compared cationic phosphine ligands containing the hydrophilic guanidinium (4.3, 4.4) and the anionic phosphine ligand TPPTS for this palladium-catalyzed coupling reaction. They found that the cationic ligands were effective for the coupling reaction but less efficient than TPPTS 43... 

Diazonium salts react with various nucleophiles in water (Eq. 11.62).106 In acidic aqueous solution, p-pheny I e ncbis di azo ni um ion reacts with alcohols more rapidly than it does with water.107 In the presence of nucelophiles such as halides, the substitution products are obtained. Furthermore, diazonium salts of aromatic compounds are excellent substrates for palladium-catalyzed coupling reactions such as the Heck-type reactions in water. 

Scheme 9 shows SvatoS s synthesis of (8Z, 10 )-tetradeca-8,10-dienal (3), the female pheromone of the horse-chestnut leafminer (Caneraria ohridella) [20]. Palladium-catalyzed coupling of A with 1-pentyne was the key-step. 

Palladium-catalyzed coupling of the borane derived from A with 1-bromo-1-pentyne to give B as well as the coupling of iodoalkene C with alkyne D were the two key-steps. 

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). 

Indoles, pyrroles, and carbazoles themselves are suitable substrates for palladium-catalyzed coupling with aryl halides. Initially, these reactions occurred readily with electron-poor aryl halides in the presence of palladium and DPPF, but reactions of unactivated aryl bromides were long, even at 120 °C. Complexes of sterically hindered alkylmonophosphines have been shown to be more active catalysts (Equation (25)). 8 102 103 In the presence of these more active catalysts, reactions of electron-poor or electron-rich aryl bromides and electron-poor or electron-neutral aryl chlorides occurred at 60-120 °C. Reactions catalyzed by complexes of most of the /-butylphosphines generated a mixture of 1- and 3-substituted indoles. In addition, 2- and 7-substituted indoles reacted with unhindered aryl halides at both the N1 and C3 positions. The 2-naphthyl di-t-butylphosphinobenzene ligand in Equation (25), however, generated a catalyst that formed predominantly the product from A-arylation in these cases. 

The palladium-catalyzed formation of sulfides can generate polyphenylene sulfide from a dithiol and a dibromoarene, or from 4-bromobenzenethiol (Equation (38)).17 In 1984 Asahi Glass obtained patents for the formation of this polymer in the presence of palladium and nickel catalysts.125,126 In addition, Gingras reported palladium-catalyzed couplings of aryl halides and thiols to form discrete phenylene sulfide oligomers.127,128 A number of polyphenylene sulfide wires, ranging from dimeric to pentameric structures, were prepared by the palladium coupling, albeit in modest yields ... 

In 1979, the reaction of styrenyl and hexenyl halides with an alkali metal thiophenolate and ethanethiolate was reported (Equation (40))130 Reaction yields exceeded 90%, and the products retained the geometry of the starting olefin. In contrast to the stereospecificity of palladium-catalyzed couplings involving vinyl halides, nickel-catalyzed couplings of vinyl halides with thiolates gave mixtures of stereoisomeric products 131... 

The dithienyldienyne 46, which was prepared by sequential palladium catalyzed couplings, underwent intramolecular annulation to compound 47 in excellent yield. Similar cyclizations involving closely related substrates were also studied <06OLl 197>. 

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