Convenient synthesis of pi-acceptor chiral stationary phases for high-performance liquid chromatography from halogen-substituted 3,5-dinitrobenzoylamides

A convenient method for the "in column" synthesis of chiral stationary phases for high-performance liquid chromatography was elaborated. It involves preparation of chiral amides of 2-bromo- or 4-chloro-substituted 3,5-dinitrobenzoic acids followed by nucleophilic substitution of the halogen in the aromatic moiety with 3-aminopropyl groups of silanized silica gel at ambient temperature. A series of pi-donor compounds, such as amides and alkyl aryl carbinols, were chromatographed on the prepared chiral stationary phases. The results were compared with data reported for chiral separations of the same substrates on similar (R)-N-(3,5-dinitrobenzoyl)-alpha-phenylglycine-derived CSP. An example of indirect enantioseparation of racemic alpha-phenylethylamine was also described using (R)-2-(2-bromo-3,5-dinitrobenzoylamino)-2-phenylethanol as a chiral derivatizing reagent.     

Palladium-catalyzed amidation of aryl halides using 2-dialkylphosphino-2'-alkoxyl-1,1'-binaphthyl as ligands

Palladium-catalyzed intermolecular C-N bond-forming reactions between aryl halides and amides are described using 2-dialkylphosphino-2'-alkoxyl-1,1'-binaphthyl, which is both bulky and electron-rich, as the ligand. A variety of amides, including aliphatic and aromatic primary amides, lactams, and carbamates, were viable substrates for the amidation, which exhibited good functional group compatibility. By tuning the substituents at the 2,2'-position of 1,1'-binaphthyl of the ligand, the palladium-catalyzed amidation of bulky aryl halides was realized and this coupling reaction was used to synthesize 2-amino-2'-methoxy-1,1'-binaphthyl in high yield.     

不对称芳基取代的方酰胺和异方酰胺的合成

Ｎ－芳基氮氧方酸的活性羟基能够被芳伯胺取代。利用这一特性，可在方酸四碳环上引入另一不同的芳胺基，即可获得不对称芳基取代的方酰胺或异方酰胺。以乙醇等为介质，芳伯胺与７种Ｎ－芳基氮方酸反应，制得２５个不对称的方酰胺和２４个不对称的异方酰胺。该合成方法优点突出，反应简便有效，通用性强。     

Preparation of tertiary amides via aryl, heteroaryl, and benzyl organozinc reagents; scope and limitations

A facile synthetic protocol for the preparation of tertiary amides has been developed. The title compounds have been successfully obtained by the Pd-catalyzed cross-coupling reactions of readily available aryl and benzyl organozinc reagents with the appropriate carbamoyl chlorides.     

Catalytic SNAr Hexafluoroisopropoxylation of Aryl Chlorides and Bromides

Fluoroalkyl aryl ethers are valuable structural motifs in pharmaceuticals because compounds with these motifs are more metabolically stable and more lipophilic than their nonfluorinated analogues. However, hexafluoroisopropyl aryl ethers have not been extensively studied, presumably because of the lack of efficient synthetic methods. Herein, we describe a rhodium-catalyzed nucleophilic aromatic substitution of aryl chlorides or bromides, which act as the limiting reagents, with weakly nucleophilic hexafluoro-2-propanol under mild reaction conditions. This method provides diverse hexafluoroisopropyl aryl ethers. We demonstrated the generality of this method by carrying out reactions of a large array of unactivated aryl halides, and we found that the success of the reactions relied on arene activation by means of η⁶-coordination.     

Electrochemical coupling of mono and dihalopyridines catalyzed by nickel complex in undivided cell

One step nickel-catalyzed electroreductive homocoupling among 2-bromopicolines and 2-bromopyridine has been investigated by our group in an undivided cell and using zinc or iron as sacrificial anode. In this work, it was developed mono and dihalopyridines coupling to obtain possible products from heterocoupling. A series of reactions were carried out in order to develop a synthetic method for the preparation of unsymmetrical 2,2′-bipyridines and 2,2′:6′,2″-terpyridines. Statistical yields (50%) were observed for 2-bromopyridines/2-bromo-6-methylpyridine heterocoupling. In a preliminary study devoted to terpyridines preparation, good results were obtained for 2,6-dihalopyridines homocoupling, affording 2,6-dichloro-2,2′-bipyridine (46%) and 2,6-dibromo-2,2′-bipyridine (56%), at controlled reaction time. At major reaction time, it was observed that the direct electroreduction of the 2,6′-dihalo-2,2′-bipyridines intermediates and 2,6″-dihalo-2,2′:6′,2″-terpyridines products on the cathode surface. A reasonable isolated product yield of 6,6″-dimethyl-2,2′:6′,2″-terpyridine (10%) was only observed in the reaction between 2,6-dichloropyridine and 2-bromo-6-methylpyridine (1:2).     

The Broad Aryl Acid Specificity of the Amide Bond Synthetase McbA Suggests Potential for the Biocatalytic Synthesis of Amides

Amide bond formation is one of the most important reactions in pharmaceutical synthetic chemistry. The development of sustainable methods for amide bond formation, including those that are catalyzed by enzymes, is therefore of significant interest. The ATP‐dependent amide bond synthetase (ABS) enzyme McbA, from Marinactinospora thermotolerans, catalyzes the formation of amides as part of the biosynthetic pathway towards the marinacarboline secondary metabolites. The reaction proceeds via an adenylate intermediate, with both adenylation and amidation steps catalyzed within one active site. In this study, McbA was applied to the synthesis of pharmaceutical‐type amides from a range of aryl carboxylic acids with partner amines provided at 1–5 molar equivalents. The structure of McbA revealed the structural determinants of aryl acid substrate tolerance and differences in conformation associated with the two half reactions catalyzed. The catalytic performance of McbA, coupled with the structure, suggest that this and other ABS enzymes may be engineered for applications in the sustainable synthesis of pharmaceutically relevant (chiral) amides.     

Aryl aminoalkyl sulfones

Two methods are proposed for the preparation of aryl aminoalkyl sulfones substituted in the aromatic ring: a method based on the oxidation of aryl aminoalkyl sulfides by hydrogen peroxide or of their bases in the presence of HClO₄ and a method based on the oxidation of aryl -chloroalkyl sulfides to chlorosulfones by hydrogen peroxide followed by their condensation with amines.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2580–2585, November, 1989.     

Palladium-Catalyzed Aminocarbonylation of Aryl Halides with N,N-Dialkylformamide Acetals

We developed a protocol for the palladium-catalyzed aminocarbonylation of aryl halides using less-toxic formamide acetals as bench-stable aminocarbonyl sources under neutral conditions. Various aryl (including heteroaryl) halides reacted with N,N-dialkylformamide acetals in the presence of a catalytic amount of tris(dibenzylideneacetone)dipalladium(0)-chloroform adduct and xantphos to give the corresponding aromatic carboxamides at 90–140 °C without any activating agents or bases in up to quantitative chemical yield. This protocol was applied to aryl bromides, aryl iodides, and trifluoromethanesulfonic acid, as well as to relatively less-reactive aryl chlorides. A wide range of functionalities on the aromatic ring of the substrates were tolerated under the aminocarbonylation conditions. The catalytic aminocarbonylation was used to prepare the insect repellent N,N-diethyl-3-methylbenzamide as well as a synthetic intermediate of the dihydrofolate reductase inhibitor triazinate.     

芳基单取代炔合成方法

综述了各种芳基单取代炔的制备方法;分析了各种方法的反应机制和特点,认为钯催化偶联-消去反应合成芳基单取代炔是比较好的方法。芳基取代聚炔及其衍生物呈现出光、电、磁等许多新颖的性能。芳基单取代炔的合成对芳基取代聚炔的制备起到关键作用。参考文献69篇。     

An efficient system for the Pd-catalyzed cross-coupling of amides and aryl chlorides

A catalyst based on a new biarylphosphine ligand (3) for the Pd-catalyzed cross-coupling reactions of amides and aryl chlorides is described. This system shows the highest turnover frequencies reported to date for these reactions, especially for aryl chloride substrates bearing an ortho substituent. An array of amides and aryl chlorides were successfully reacted in good to excellent yields.     

Poly(aryl ether amide)s

A general method for the preparation of poly(aryl ether amide)s has been developed where the generation of an aryl ether linkage is the polymer-forming reaction. The amide linkage was found to be sufficiently electron-withdrawing to activate halo-substituents towards nucleophilic aromatic substitution analogous to conventional activating groups (i.e., sulfone, ketone, etc.). Model reactions demonstrated that the amide-activated displacement occurred with high selectivity in near quantitative yield and was judged suitable as a polymer-forming reaction. Appropriately fluoro-substituted amides were prepared and subjected to displacement polymerization with bisphenoxides in a N-methyl-2-pyrrolidone (NMP)/N-cyclohexyl-2-pyrrolidone (CHP) solvent mixture. High molecular weight polymers with glass transition temperatures in the 200–225°C range were obtained. © 1993 John Wiley & Sons, Inc.     

Wet cyanuric chloride promoted efficient synthesis of amidoalkyl naphthols under solvent-free conditions

An efficient and direct procedure has been developed for the preparation of amidoalkyl naphthols by a one-pot condensation of aryl aldehydes.2-naphthol and area or amides,in the presence of wet-cyanuric chloride(wet-TCT)as a catalyst.The reactions were carried out under solvent.flee media.The present methodology offers several advantages such as excellent yields,simple procedure and eco-friendly reaction condition.     

Synthesis of primary aromatic amides by aminocarbonylation of aryl halides using formamide as an ammonia synthon

Primary aromatic amides were prepared by a palladium-catalyzed aminocarbonylation reaction of aryl halides in high yields (70-90%) using formamide as the amine source. The reactions require a palladium catalyst in combination with a nucleophilic Lewis base such as imidazole or 4-(dimethylamino)pyridine (DMAP). Aryl, heteroaryl, and vinyl bromides and chlorides were converted to the primary amides under mild conditions (5 bar, 120 degrees C) using 1 mol % of a palladium-phosphine complex. Best results were obtained in dioxane using triphenylphosphine as the ligand and DMAP as the base. For activated aryl bromides, a phosphine-to-palladium ratio of 2:1 was sufficient, but less reactive aryl bromides or aryl chlorides required ligand-to-palladium ratios up to 8:1 in order to stabilize the catalyst and achieve full conversion. The influence of catalyst, base, solvent, pressure, and temperature was studied in detail. The mechanism of the reaction could be clarified by isolating and identifying the reaction intermediates. In addition, methylamides and dimethylamides were prepared by the same method using N-methylformamide and N,N-dimethylformamide as the amine source.     

Palladacycle-Catalyzed Carbonylation of Aryl Iodides or Bromides with Aryl Formates

An efficient palladacycle-catalyzed aromatic carbonylation reaction of aryl formates with aryl iodides or bromides has been developed. Commercially available and easily prepared aryl formates were employed as carbonyl sources without the use of external carbon monoxide. The present catalytic system shows broad functional group tolerance and affords aryl benzoate derivatives in good to excellent yields.     

Reduction of Aryl Thiocyanates with SmI(2) and Pd-Catalyzed Coupling with Aryl Halides as a Route to Mixed Aryl Sulfides

A series of aryl iodides, with a range of substituents, has been successfully coupled using 10 mol % Pd catalyst with samarium thiolates, derived from the corresponding aryl thiocyanates upon reductive cleavage with SmI(2). Reactions proceed in THF at 65 degrees C in yields ranging from good to excellent and are compatible with both electron-donating and electron-withdrawing substituents, except NO(2). The reactions may also be conducted with aryl bromides although with somewhat lower yields.     

Preparation of 5-brominated and 5,5'-dibrominated 2,2'-bipyridines and 2,2'-bipyrimidines.

Efficient syntheses of 5-brominated and 5,5'-dibrominated 2,2'-bipyridines and 2,2'-bipyrimidines, useful for the preparation of metal-complexing molecular rods, have been developed. 5-Bromo-2,2'-bipyridine, 5-bromo-5'-n-butyl-2,2'-bipyridine, and 5-bromo-5'-n-hexyl-2,2'-bipyridine were obtained by Stille coupling of 2,5-dibromopyridine with 2-trimethylstannylpyridine or the requisite 5-alkyl-2-trimethylstannylpyridine, obtained via regioselective zincation of a 3-alkylpyridine.BF(3) complex in the less hindered of the two reactive positions with lithium di-tert-butyl-(2,2,6,6-tetramethylpiperidino)zincate. 5,5'-Dibromo-2,2'-bipyridine was obtained by the reductive symmetric coupling of 2,5-dibromopyridine with hexa-n-butyldistannane. The yields of these coupling reactions ranged from 70 to 90%. 5-Bromo- and 5,5'-dibromo-2,2'-bipyrimidines were obtained in yields of 30 and 15%, respectively, by bromination of 2,2'-bipyrimidine, prepared from 2-chloropyrimidine in 80% yield by an improved reductive symmetric coupling procedure.     

Easy-to-execute carbonylations: microwave synthesis of acyl sulfonamides using Mo(CO)(6) as a solid carbon monoxide source

The development of a robust palladium-catalyzed amidocarbonylation protocol for the preparation of aromatic acyl sulfonamides utilizing high-density microwave heating is described. This synthetic approach employs Mo(CO)(6) as a convenient CO-releasing reagent and allows for the direct preparation of acyl sulfonamides from both aryl iodides and aryl bromides. The reactions can be performed under air, employing only 15 min of microwave irradiation, to produce acyl sulfonamide derivatives in good to excellent yields. To illustrate the usefulness of this method, we reported the synthesis of a novel hepatitis C virus NS3 protease inhibitor.     

Rhodium-Catalyzed Addition of Aryl Boronic Acids to 2,2-Disubstituted Malononitriles

β-Ketonitriles bearing a quaternary carbon at the 2-position were prepared through Rh-catalyzed addition of aryl boronic acids to 2,2-disubstituted malononitriles. In contrast to the previously described transnitrilative cyanation of aryl boronic acids with dialkylmalononitriles, the present reaction avoids retro-Thorpe collapse of the intermediate addition product through the use of a milder base. The reaction was amenable to a variety of aryl boronic acids and disubstituted malononitriles, providing a diverse array of β-ketonitriles. The products could be further derivatized to valuable chiral α,α-disubstituted-β-aminonitriles through addition reactions to the corresponding N-tert-butanesulfinyl imines.     

Silica supported perchloric acid （HClO4-SiO2）： A mild,reusable and highly efficient heterogeneous catalyst for the synthesis of amidoalkyl naphthols

An efficient and direct procedure has been developed for the preparation of amidoalkyl naphthols by a one-pot condensation of aryl aldehydes, 2-naphthol and urea or amides, in the presence of HClO4-SiO2 as a heterogeneous catalyst. The reactions were carried out under reflux and solvent-free conditions. The present methodology offers several advantages such as excellent yields, simple procedure, easy work-up and ecofriendly reaction condition. The catalyst is easily prepared, stable, reusable and efficient under the reaction conditions.