High-yielding intramolecular direct arylation reactions with aryl chlorides

[reaction: see text] An N-heterocyclic carbene palladium catalyst system is used to promote direct arylation of a broad range of aryl chlorides to form six- and five-membered ring biaryls. An influence of the halide on the palladium precatalyst on catalyst activation has been revealed, as has a beneficial effect of NHC salts that allows the turnover numbers to be increased by simple addition of imidazolium salts to the reaction mixture.     

Copper-mediated direct arylation of benzoazoles with aryl iodides

The direct arylation of 1,3-benzoazole compounds with aryl iodides is effectively promoted by CuI with use of PPh₃ and Na₂CO₃ or K₃PO₄ as ligand and base, respectively, in DMF or DMSO to produce the corresponding 2-arylated products with good yields.     

Palladium-catalyzed cross-coupling of pyrrole anions with aryl chlorides, bromides, and iodides

[reaction: see text] A general method for the conversion of pyrrole anions to 2-arylpyrroles has been developed. Using a palladium precatalyst and sterically demanding 2-(dialkylphosphino)biphenyl ligands, (pyrrolyl)zinc chloride may be cross-coupled with a wide range of aryl halides, including aryl chlorides and aryl bromides, at low catalyst loadings and under mild conditions. A high degree of steric hindrance is tolerated. Certain ring-substituted pyrrole anions have also been arylated with aryl bromide substrates.     

Palladium-catalyzed direct arylation of thiazoles with aryl bromides

Thiazole, 2-phenyl or -alkyl substituted one and benzothiazole are efficiently arylated with aryl bromides at the 2- and/or 5-position(s) in the presence of Pd(OAc)₂ and a bulky phosphine ligand using Cs₂CO₃ as base. 2-Phenyl-5-thiazolecarboxanilide undergoes successive diarylation at the 4- and 5-positions accompanied by decarbamoylation.     

Application of a new bicyclic triaminophosphine ligand in Pd-catalyzed Buchwald-Hartwig amination reactions of aryl chlorides, bromides, and iodides

The new bicyclic triaminophosphine ligand P(i-BuNCH2)3CMe (3) has been synthesized in three steps from commercially available materials and its efficacy in palladium-catalyzed reactions of aryl halides with an array of amines has been demonstrated. Electron-poor, electron-neutral, and electron-rich aryl bromides, chlorides, and iodides participated in the process. The reactions encompassed aromatic amines (primary or secondary) and secondary amines (cyclic or acyclic). It has also been shown that the weak base Cs2CO3 can be employed with ligand 3, allowing a variety of functionalized substrates (e.g., those containing esters and nitro groups) to be utilized in our amination protocols. This ligand provides a remarkably general, efficient, and mild palladium catalyst for aryl iodide amination. Although 3 is slightly air and moisture sensitive, easy procedures can be adopted that avoid the need of a glovebox. Comparisons of the efficacy of 3 in these reactions with that of the proazaphosphatrane P(i-BuNCH2CH2)3N (2) reveal that in addition to the opportunity for transannulation in 2 (but not in 3), other significant stereoelectronic contrasts exist between these two ligands which help account for differences in the activities of the Pd/2 and Pd/3 catalytic systems.     

Cobalt-Xantphos-catalyzed, LiCl-mediated preparation of arylzinc reagents from aryl iodides, bromides, and chlorides

A cobalt-Xantphos-catalyzed, LiCl-mediated system has been developed for the direct and expedient preparation of arylzinc reagents in THF from the corresponding aryl iodides, bromides, and chlorides. Owing to the use of THF as a versatile solvent, the thus-formed arylzinc reagents displayed a high degree of compatibility with a variety of conventional as well as newly emerging metal-catalyzed cross-coupling reactions.     

Rhodium-HMPT-catalyzed direct ortho arylation of phenols with aryl bromides

Direct ortho arylation of phenols with aryl bromides catalyzed by a rhodium complex and hexamethylphosphorous triamide (HMPT) have been developed. A plausible reaction mechanism involving in situ generation of arylphosphites from phenols and HMPT, phosphorus-directed ortho metalation, and transesterification of the arylated arylphosphites with the substrate phenols is proposed.     

Ultramicro detection of chlorides,bromides and iodides

Summary An ultramicro method for the detection of iodide, chloride and bromide, either alone or in each others presence is described. The method can also be applied to the detection of these halogens in organic compounds. As little as 0.01% of one halide can be detected in the presence of 2–3% of the others.

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Zusammenfassung Eine Ultramikromethode zum Nachweis von Jodid, Chlorid und Bromid, allein oder bei gleichzeitiger Anwesenheit, wurde beschrieben. Das Verfahren eignet sich auch zum Nachweis dieser Halogene in organischen Verbindungen. 0,01% eines der Halogene ist bei Gegenwart von 2 bis 3% der anderen nachweisbar.

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Résumé On décrit une méthode ultramicro pour la détection des iodures, chlorures et bromures, soit seuls soit en présence les uns des autres. La méthode peut aussi s'appliquer pour déceler ces halogènes dans les composés organiques. On peut mettre en évidence jusqu'à 0,01% d'un halogénure en présence de 2–3% des autres.

     

Palladium-catalyzed cross-coupling reactions of heterocyclic silanolates with substituted aryl iodides and bromides

[reaction: see text] Sodium silanolates derived from a number of heterocyclic silanols undergo cross-coupling with a variety of aromatic iodides and bromides under mild conditions. In situ deprotonation of the silanols with an equivalent amount of sodium hydride in toluene generates the sodium salt that couples with iodides under the action of Pd(2)(dba)(3).CHCl(3) in good yield at room temperature to 50 degrees C. The aromatic bromides also couple with these salts under the action of the Pd(I) catalyst 12.     

Highly efficient synthesis of phenols by copper-catalyzed hydroxylation of aryl iodides, bromides, and chlorides

8-Hydroxyquinolin-N-oxide was found to be a very efficient ligand for the copper-catalyzed hydroxylation of aryl iodides, aryl bromides, or aryl chlorides under mild reaction conditions. This methodology provides a direct transformation of aryl halides to phenols and to alkyl aryl ethers. The inexpensive catalytic system showed great functional group tolerance and excellent selectivity.     

High stereoselectivity in chelation-controlled intermolecular Heck reactions with aryl chlorides, vinyl chlorides and vinyl triflates

Highly stereoselective chelation-controlled Pd(0)-catalyzed beta-arylations and beta-vinylations of a five-membered chiral, pyrrolidine-based vinyl ether were achieved using aryl- and vinyl chlorides as substrates, yielding quaternary 2-aryl/vinyl-2-methyl cyclopentanones in 89-96% ee under neutral reaction conditions.     

Mild and efficient palladium-catalyzed intramolecular direct arylation reactions

The influence of ligand, stoichiometric base, and additive has been evaluated in the context of intramolecular direct arylation reactions. Under the optimal conditions, arylation of simple arenes can be performed under very mild conditions, with heating to 50 °C. The role of the pivalic acid additive is rationalized by invoking a concerted palladation-deprotonation pathway where the pivalate is behaving as either an intramolecular base from the palladium metal or through an intermolecular deprotonation in a similar manner as that previously described by Echavarren and Maseras.     

Palladium-catalyzed N-arylation of sulfoximines with aryl bromides and aryl iodides

Various N-arylated sulfoximines have been synthesized in high yield by a direct approach which is based on a palladium-catalyzed cross-coupling strategy. Aryl bromides of variable substitution pattern were found to be the most effective coupling partners, whereas aryl iodides showed a nonpredictable behavior requiring lithium or silver salts as additives to ensure product formation in acceptable yields. Coupling of (S)-2-(2'-bromophenyl)-4-tert-butyloxazoline with enantiomerically pure (-)-(RS)-S-methyl-S-phenylsulfoximine afforded the corresponding product in good yield as a single diastereomer, showing that the palladium-catalyzed arylation proceeds in a stereospecific manner. The reaction with dibromobenzenes yielded the monosulfonimidoyl arenes in all cases, suggesting that the introduction of the sulfonimidoyl moiety deactivates the arene, thus preventing a second coupling step.     

Palladium-catalyzed negishi cross-coupling reactions of unactivated alkyl iodides, bromides, chlorides, and tosylates

A single method (2% Pd(2)(dba)(3)/8% PCyp(3)/NMI in THF/NMP at 80 degrees C; Cyp = cyclopentyl) achieves the cross-coupling of a range of beta-hydrogen-containing primary alkyl iodides, bromides, chlorides, and tosylates with an array of alkyl-, alkenyl-, and arylzinc halides. The process is compatible with a variety of functional groups, including esters, amides, imides, nitriles, and heterocycles.     

Zinc-mediated intramolecular acyl and imino transfer reactions of aryl iodides

A method for the coupling of acyl and imino substituents to the sterically encumbered 5-position of a 4-aminoquinazoline was developed. Starting with a 4-amino-5-iodoquinazoline, the method employs a facile intramolecular zinc-mediated transfer from the 4-amino group to the iodo-bearing carbon. The method was found to be effective for a variety of substituents, in particular a pyridyl group required for the synthesis of Pfizer’s prostate selective α₁ antagonist candidate for the treatment of benign prostatic hyperplasia, UK-338,003.     

Efficient copper-catalyzed N-arylation of sulfoximines with aryl iodides and aryl bromides

Two simple and inexpensive systems for copper-catalyzed N-arylations of sulfoximines with aryl bromides and aryl iodides have been developed. Using 10 mol % of a copper(I) salt in combination with 20 mol % of a 1,2-diamine and Cs2CO3 provides N-arylated sulfoximines in high yields. Various functional groups and heteroatoms are tolerated. The method is complementary to the known protocols for N-arylations of sulfoximines, which require stoichiometric quantities of copper salts or cost-intensive palladium/BINAP catalysts.