Pyridines palladium® acetate

The TV-protected 3-amino-2-chloropyridine derivative in 7.45. for example was found to react with styrene in the presence of a palladium acetate-triphenylphosphine catalyst system at elevated temperatures to give a near quantitative yield of a single coupling product.64 In the process sodium acetate was used as base. The formation of a single regioisomer might be attributed to the steric bulk of pyridine s substituents in position 3. 

The Heck reactions depicted so far all involve the coupling of halopyridines and other olefins. The alternate approach, coupling of a vinylpyridine with an aryl halide is also feasible, although less commonly employed. 4-Vinylpyridine was coupled successfully with diethyl 4-bromobenzylphosphonate (7.50.) in the presence of a highly active catalyst system consisting of palladium acetate and tn-o-tolylphosphine to give the desired product in 89% yield, which was used for grafting the pyridine moiety onto metal oxides.70... 

Pd-catalysed chelate-directed acetoxylation of meta -substituted arenes has been studied.61 Many substituted groups are tolerated by this process and the reaction shows a high degree of regioselectivity for the less sterically hindered ortfto-position. For example, 2-(3-nitrophenyl)pyridine forms 2-(2-acetoxy-3-nitrophenyl)pyridine. Finally, density functional calculations62 on the palladium acetate-promoted cyclomet-allation of dimethylbenzylamine suggest that reaction occurs via an agostic C-H complex rather than a Wheland intermediate. An intramolecular H-transfer to a coordinated acetate via a six-membered transition state follows. 

A highly regioselective hydroselenation of terminal alkynes RC=CII with benzene-selenol (PhSeH) can be achieved in the presence of palladium acetate as catalyst in pyridine, giving rise to the corresponding terminal alkenes R(PhSe)CH=CH2 as the sole products. Here, the pyridine is believed to serve as a ligand for active palladium intermediates.67... 

An exception involves the passage of hot alcohol vapors over thorium oxide at 350-450°C, under which conditions Hofmann s mle is followed, and the mechanism is probably different. Cyclobutanol derivatives can be opened in the presence of a palladium catalyst. 2-Phenylbicyclo[3.2.0]octan-2-ol, for example, reacted with a catalytic amount of palladium acetate in the presence of pyridine and oxygen to give phenyl methylenecyclohexane ketone. ... 

The use of palladium and ruthenium as halogen-free carbonylation catalysts has been studied intensively by Shell. The catalysts were principally designed for the carbonylation of olefins in the presence of alcohols in order to yield carboxylic esters [26], but work also well for the synthesis of carboxylic acids or anhydrides. The latter are formed when the reaction is conducted in an acid as a solvent [27]. The palladium systems typically consist of palladium acetate, tertiary phosphines, and strong acids such as mineral acids or acids with weak or noncoordinating anions such as p-toluenesulfonic acid. Remarkable activities are achieved when aromatic phosphines that carry pyridines as substituents are... 

Cavallito (66) reports that neither it nor 3-benzoxypyridine was hydrogenated in the presence of Willstatter s palladium sponge catalyst (67). Under low pressure conditions in ether or dioxane Raney nickel and platinum oxide were ineffective. However, other examples show that reduction takes place readily under a variety of conditions. Biel used Raney nickel at 125° and 50 atm (68), excellent yield of 6-propyl-3-hydroxypiperidine resulted from reduction of the pyridine in acetic acid with platinum oxide (69). Ruthenium in the conversion of 3-hydroxypyridine in aqueous solution gave very high yield of the corre-... 

Regioselective functionalization of unreactive carbon-hydrogen bonds, in particular, arylation of pyridines by using aryl iodide, silver acetate, and catalytic palladium acetate 06SL3382. 

Carbamates and ureas are easily prepared and separated from the oxidative carbonylation of amines catalyzed by [PdCl2(phenanthroline)] dissolved in [G4GiIm]BF4. The carbonylation of terminal 3-alkyn-l-ols and l-alkyn-4-ols by palladium acetate/2-(diphenylphosphino)pyridine dissolved in [G4CiIm]PF6 or [C4CiIm]BF4 affords quantitatively and selectively v< -a-methylene (Scheme 21) and 7- and -lactones, respectively. ... 

The first reaction is catalyzed by palladium acetate. It takes place in the presence of pyridine, as a base, and copper acetate, as oxidant, thus resulting in indolyl-substituted imidazoles with the retention of the Al-oxide moiety (Scheme 70) [212],... 

Arylation of Quinoline N-Oxides and Pyridines N-Oxides. An efficient protocol to directly arylate quinoline A-oxides was developed using palladium acetate as the catalyst and potassium carbonate as the hase. A survey of different phosphines demonstrated that the sterically less encumbered di-tert-butyl(methyl)phosphonium tetrafluoroborate provides higher yields relative to tri-iert-hutylphosphine. Using this protocol, 15 quinohne A-oxides were arylated in good to excellent yields (eq 1). ... 

A modified protocol involving pivahc acid as an additive was developed in order to perform the arylation of pyridine A-oxides with aryl triflates as the electrophile. Similar to other Het-H functionalization reactions, palladium acetate is used as the catalyst in conjunction with di-/eri-hutyl(methyl)phosphonium tetrafluoroborate as the ligand, leading to the efficient arylation of a diverse set of pyridine (eq 4), pyridazine (eq 5), pyrimidine (eq 6), and pyrazine A-oxides (eq 7). This method also minimizes... 

Arylation with bromobenzene of the activated pyridine is then carried out in the presence of palladium acetate (5 mol %), tri-r-butylphosphine (15 mol%), and potassium carbonate under anhydrous conditions. The arylated. V-iminopyridinium ylide is afforded in 80% yield as a sole isomer and it can be reduced efficiently to the corresponding pyridine under known conditions. Interestingly, the competition experiment to compare the difference of reactivity between pyridine iV-oxide and the V-iminopyridinium ylide shows that pyridine iV-oxide is not arylated, while 56% of arylated V-iminopyridinium ylide is obtained. In addition, bis-arylation is observed in less than 10% yield. These... 

Palladium-catalyzed Arylation of Pyridine N-Oxides and N-Iminopyridinium Ylides. Tri-tert-butylphosphine has been used in the palladium-catalyzed C-arylation of pyridine 7/-oxides and derivatives. Using palladium acetate as the catalyst, tri-tert-butylphosphine as the ligand, and 3-bromopyridine as the electrophile, the C-H arylation of pyridine tV-oxide was accomplished, yielding the 2-arylated compound as the major product and the 2,6-diarylated pyridine as a minor product (eq 24). ... 

Palladium-catalyzed Direct Arylation of Pyridine N-Oxides, Pyrazine N-Oxides, Pyridazine N-Oxides, Pyrimidine N-Oxides, and Thiazole N-Oxides. Pyridine W-oxides can be efficiently ary-lated at the C2 position using aryl halides as the electrophile, palladium acetate as the catalyst, tri-tert-butylphosphonium tetraflu-oroborate as the ligand, and potassium carbonate as the base (eq 19). In this protocol, 3 equiv of pyridine Al-oxide are utilized to generate the corresponding 2-aryl derivatives. ... 

Condensation of l-bromo-2-methoxy-4-methyl benzene (64) with 5,6-dimethoxyaniline acetate (65) in pyridine in the presence of Cu and K2CO3 and subsequent hydrolysis with 20% KOH furnished the di-phenylamine derivative (66) which on treatment with palladium acetate in DMF afforded murrayastine (13). Condensation of l-bromo-3-methoxy-4-methylbenzene (67) with the dimethyl acetal of 6-formyl-5-methoxyaniline acetate (68) furnished the diphenylamine derivative (69) which on hydrolysis and on subsequent cyclisation furnished murray-aline (14). 

In 2011, the same group reported unprecedented C3-selective functionalization of pyridine derivatives. The oxidative coupling catalyzed by palladium acetate/l,10-phenanthroline/Ag2CO3 under air afforded the desired olefination product in up to good yields (Scheme 9.7). Moreover, a significant kinetic isotope effect was observed, which is consistent with metal-mediated C-H bond cleavage. 

The use of transition metal catalysts to effect alkylations, alkenylations, arylations, and acylations in pyridines has been reviewed, and there has been a computational study of the ortho-alkylation of pyridine by scandium-catalysed reactions with alkenes. DFT calculations indicate that the stability of the developing metal-aryl bonds may be important in determining regioselectivity in palladium-acetate-catalysed carbon-hydrogen substitution in heteroarenes. ... 

The palladium-catalysed reaction of the pyrazolo-pyrimidine derivative (141) with 3-bromotoluene may result in arylation at the 3-position in the pyrazole ring or at an sp hybridized site in the 7-methyl side-chain depending on the base and ligands used. After initial insertion of the palladium catalyst into the aryl halide bond, palladation of (141) occurs by a concerted metalation-deprotonation pathway and is followed by reductive elimination. Concerted metalation-deprotonation is also likely in the palladium-acetate-catalysed reaction of imidazo[l,2-a]pyridines with aryl bromides to give 3-substituted derivatives such as (142). A careful mechanistic study of the arylation of pyridine A-oxide by bromotoluene, catalysed by palladium acetate and t-butylphosphine, has shown that direct reactions of an aryl palladium complex with... 

Methylphenyl)benzothiazole (80IC762) and 2-benzylbenzothiazole (95ICA(239)125) can be cyclopalladated. In the latter case, cylopalladation occurs upon reaction with palladium(II) acetate and gives the product 80. With lithium chloride, sodium bromide, or sodium iodide, a series of three products of substitution of the acetate group 81 (X = C1, Br, I) results. Pyridine, 2- and 3-methylpyridine, 2,6- and 3,5-dimethylpyridine cause the transformation of the chelate complexes 81 (X = C1, Br, I) and formation of the mononuclear products 82 (R = z= R" = = R = H, X = Cl, Br, I ... 

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