Palladium-catalyzed Coupling Reaction Research Articles

Synthetic Approaches to Tetracyclic Indolines as Versatile Building Blocks of Diverse Indole Alkaloids.

Indole alkaloids bearing the tetracyclic indoline scaffolds of 1H-pyrrolo[2,3-d]carbazole have shown fascinating chemical diversity and significant biological activities. The development of efficient synthetic methodologies for such a tetracyclic scaffold remains highly desirable in both synthetic chemistry and medicinal chemistry. This review outlines key strategies for the construction of the tetracyclic indoline scaffolds in total syntheses of many indole alkaloids. The key strategies include nucleophilic additions, Diels-Alder reactions, radical cyclizations, and palladium-catalyzed coupling reactions. The representative examples and their applications in the total syntheses are described here and discussed in depth.

A low band gap diketopyrrolopyrrole-based polymer: Synthesis, thermal and optical properties

ABSTRACTIn this work, P-DPP, which was a low band gap polymer based on diketopyrrolopyrrole (DPP) and cyclopentadithiophene (CPDT), was synthesized through palladium-catalyzed Stille coupling reaction. Due to the strong electron-donating property of CPDT and strong withdrawing property of DPP, P-DPP exhibited narrow band gap of 1.29 eV. The thermal and optical properties of P-DPP had been carefully investigated.

Correction to "Catalyst Selection Facilitates the Use of Heterocyclic Sulfinates as General Nucleophilic Coupling Partners in Palladium-Catalyzed Coupling Reactions".

Correction to "Catalyst Selection Facilitates the Use of Heterocyclic Sulfinates as General Nucleophilic Coupling Partners in Palladium-Catalyzed Coupling Reactions".

Design and synthesis of 2,6-disubstituted-8-amino imidazo[1,2a]pyridines, a promising privileged structure

Imidazo[1,2a]pyridines have gained much interest in the field of medicinal chemistry research. In the aim of accessing new privileged structure, we decided to design and synthesize 8-aminated-imidazo[1,2a]pyridines substituted on positions 2 and 6. This scaffold, rarely found in the literature, was obtained via palladium-catalyzed coupling reactions (Suzuki reaction or N-hydroxysuccinimidyl activated ester method) and tested on adenosine receptor A2A. We demonstrated how incorporation of an exocyclic amine enhanced affinity towards this receptor while maintaining low cytotoxicity.

Β-Arylamino Functionalized Porphyrins: Regioselective Synthesis, Structural, Photophysical and Electrochemical Properties

Among the different approaches for β-functionlization of poprhyrins, a limited number of β-arylamino functionalized poprhyirns were reported.1 Porhyrins and metallopoprhyrins that consist arylamino group have exhibited unique physiochemical and electrochemical redox properties and utilized for various applications such as dye-sensitized solar cells (DSSCs), catalysis, and nonlinear optics.2 In this regard, we report the regioselective synthesis of 2-arylamino-12,13-dibromo-5,10,15,20-tetraphenylporphyrins and their metal (Cu(II) and Zn(II)) complexes (Fig. 1a). The palladium catalyzed coupling reaction of tetrabromoporphyrin with substituted anilines yielded various mono-β-arylamino substituted poprhyrins. All β-arylamino porphyrins were characterized by UV-Vis, fluorescence, 1H NMR spectroscopic techniques and cyclic voltammetry studies. β-arylamino porphyrins exhibited broadened absorption spectra which consist one Soret and two Q bands as shown in Fig. 1b. Notably, β-arylamino porphyrins exhibited multiple oxidations and reductions due to 'push-pull' β-substituents which alters the energy levels of frontier molecular orbitals. DFT studies revealed that these porphyrins are having quasiplanar confirmation. In this presentation, we will discuss about the regioselective synthesis, spectral, electrochemical redox properties of β-arylamino functionalized porphyrins in detail. Figure 1

Palladium-Catalyzed Esterification of Carboxylic Acids with Aryl Iodides.

The first palladium-catalyzed esterification of carboxylic acids with aryl iodides is described. A palladium-based catalytic system consisting of IBnF (1,3-bis((pentafluorophenyl)methyl)imidazole-2-ylidene) ligand was found to significantly accelerate the aryl-O bond-forming esterification reaction. A series of aryl iodides and carboxylic acids undergoes a palladium-catalyzed coupling reaction to provide the corresponding aryl esters in moderate to good yields. In addition, sterically hindered aryl iodides and carboxylic acids were well-tolerated yielding the corresponding aryl esters.

Palladium-Catalyzed Decarboxylative Heck-Type Coupling of Activated Aliphatic Carboxylic Acids Enabled by Visible Light.

The palladium-catalyzed coupling reaction of N-hydroxyphthalimide esters and styrenes to deliver exclusively (E)-substituted olefins under irradiation with visible light is reported. This method tolerates N-hydroxyphthalimide esters derived from primary, secondary, tertiary as well as benzylic carboxylic acids. Notably, Pd(PPh3 )4 is employed as an inexpensive palladium source and no addition of base or classical photocatalyst is required. Mechanistic studies suggest a light-mediated single-electron reduction of the activated acid by a photoexcited palladium(0) species to access alkyl radicals through decarboxylation.

Synthesis of cis-5,5a,6,10b-Tetrahydroindeno[2,1-b]indoles through Palladium-Catalyzed Decarboxylative Coupling of Vinyl Benzoxazinanones with Arynes.

A novel palladium-catalyzed decarboxylative coupling reaction of vinyl benzoxazinanones with arynes which may feature an intramolecular nucleophilic attack of an amino group at the central carbon of π-allylpalladium intermediate has been developed. The cis-5,5a,6,10b-tetrahydroindeno[2,1-b]indoles were generated in moderate to good yields. One key to the success of the present reaction was to achieve comparable rates for the palladium-catalyzed decarboxylation and aryne formation steps.

Synthesis and Evaluation of Pyridyloxypyridyl Indole Carboxamides as Potential PET Imaging Agents for 5-HT2C Receptors

Nine pyridyloxypyridyl indole carboxamides were synthesized and displayed high affinities for 5-HT2C receptors and high selectivity over 5-HT2A and 5-HT2B. Among them, 6-methyl-N-[6-[(2-methyl-3-pyridinyl)oxy]-3-pyridinyl]1H-indole-3-carboxamide (8) exhibits the highest 5-HT2C binding affinity (Ki = 1.3 nM) and high selectivity over 5-HT2A (∼1000 times) and 5-HT2B (∼140 times). [11C]8 was synthesized by palladium-catalyzed coupling reaction between pinacolboranate 16 and [11C]CH3I with an average radiochemical yield of 27 ± 4% (n = 8, decay-corrected from end of [11C]CH3I synthesis). MicroPET imaging studies in rhesus monkeys showed regional uptake of [11C]8 in the choroid plexus, whereas the bindings in all other brain regions were low. The specific binding in the choroid plexus was confirmed by administration of a blocking dose of 0.1 mg/kg of the 5-HT2C antagonist SB-242084.

Synthesis of 4-Aryl Isoquinolinedione Derivatives by a Palladium-Catalyzed Coupling Reaction of Aryl Halides with Isoquinoline-1,3(2 H,4 H)-diones.

The palladium-catalyzed cross-coupling reaction of aryl halides with isoquinoline-1,3(2 H,4 H)-diones for the synthesis of 4-aryl isoquinoline-1,3(2 H,4 H)-diones was developed. The reaction conditions exhibit remarkable compatibility with various aryl halides and isoquinoline-1,3(2 H,4 H)-diones, and the product could be conveniently transformed to 4-aryl tetrahydroisoquinolines. (±) Dichlorofensine was synthesized using this protocol in two steps with an overall yield of 71%.

P450-Catalyzed Regio- and Stereoselective Oxidative Hydroxylation of 6-Iodotetralone: Preparative-Scale Synthesis of a Key Intermediate for Pd-Catalyzed Transformations.

Chiral alcohols are important building blocks for the production of pharmaceuticals, catalytic access being possible by the use of enzymes, transition metal catalysts, or organocatalysts. Herein we report the use of cytochrome P450-BM3 mutants for the oxidative hydroxylation of 6-iodotetralone regio- and enantioselectively at C4 with formation of the ( R)-alcohol. This CH activation is not possible using modern synthetic catalysts. The synthetic utility of this valuable synthon was explored in palladium-catalyzed coupling reactions that occur in the absence of undesired racemization.

Synthesis of multi-substituted dihydrofurans via palladium-catalysed coupling between 2,3-alkadienols and pronucleophiles.

Multi-substituted dihydrofurans were obtained from a palladium-catalysed coupling reaction between 2,3-alkadienols and ketones bearing an electron-withdrawing group at the α-position. Methanol as a solvent was essential for the initial dehydrative substitution to suppress the competitive hydroalkylation of the diene moiety. The substitution would be followed by intramolecular hydroalkoxylation under the same catalysis.

One-pot synthesis of new $N$-(1-methylpyridin-4(1$H)$-ylidene)amine ligands for palladium-catalyzed Heck coupling reaction

A series of new derivatives of N-(1-methylpyridin-4(1H)-ylidene)amines, [L1]-[L5], were synthesized and characterized by FTIR, NMR, MS, and XRD analysis. These targeted compounds were synthesized by the melt reaction between N-methylated-4-chloropyridinium triflate and corresponding amines (1-naphthyl amine, o-ansidine, 2-nitroaniline, p-ansidine, and cyclohexyl amine) followed by the addition of sodium hydride in dichloromethane in the same pot. These highly electron-donating N-(1-methylpyridin-4(1H)-ylidene)amine ligands considerably improve the catalytic activity of palladium acetate towards Heck-Mizoroki carbon-carbon cross-coupling reactions.

Synthesis of imidazopyridine-fused indoles via one-pot sequential Knoevenagel condensation and cross dehydrogenative coupling.

A simple and efficient strategy for the synthesis of imidazopyridine-fused indoles has been developed that involves one-pot sequential Knoevenagel condensation of readily available active methylene azoles with N-substituted-1H-indole-3-carboxaldehydes or N-substituted-1H-indole-2-carboxaldehydes followed by palladium-catalyzed intramolecular cross dehydrogenative coupling reaction. A series of 36 derivatives was prepared by using this strategy. The products were obtained in moderate to excellent (32-94%) yields and showed broad substrate scope with tolerance of various functional groups and was amiable for gram scale preparation without problems.

Bromination of the benzothioxanthene Bloc: toward new π-conjugated systems for organic electronic applications

The synthesis for monobrominated benzothioxanthene is reported, which is then employed in common palladium catalyzed coupling reactions for novel organic semiconductors.

Palladium catalyzed chloroethoxylation of aromatic and heteroaromatic chlorides: an orthogonal functionalization of a chloroethoxy linker.

A novel disconnection based on cross-coupling chemistry was designed to access pharmaceutically relevant aryl-aminoethyl ethers. The developed palladium-catalyzed functionalization of aryl- and heteroaryl chlorides with a sodium tetrakis-(2-chloroethoxy) borate salt is orthogonal to the simple nucleophilic replacement of the chloro function of the ethylene linker. The transformation enables efficient 2-chloroethoxylation in the absence of an additional external base. Subsequent amine substitution of the alkyl halide affords 2-aminoethoxy arenes. The applicability of this method was demonstrated through the synthesis of various aryl- and heteroaryl-alkyl ethers, including the intermediates of marketed drug molecules.

Enhancement of thermal stability and photoluminescent performance of blue light emitting material by incorporating adamantane moieties into carbazole system

ABSTRACTA facile route to improve photoluminescent performance and service lifetime of a promising blue light emitting material is reported and demonstrated here using a copolymer system of N-(2-ethylhexyl)-2,7-carbazole (Cz) and 1,3,5,7-tetrakis- (4-bromophenyl) adamantane (TBA). The copolymers were successfully synthesized by palladium-catalyzed Suzuki coupling reactions. Structure and molecular weight of the materials were characterized by FT-IR and 1H-NMR spectroscopies, elemental analysis and gel permeation chromatography. The influence of adamantane content on the thermal stability and photoluminescent performance of the synthesized copolymers was investigated in detail. DSC results showed that glass transition temperature increased dramatically, from 68°C for neat carbazole, to 88°C, 120°C and 152°C, after the addition of 10%, 20%, and 30% TBA, respectively. The same trend was found when thermal decomposition temperature at 5% weight loss was evaluated from TGA data. Importantly, this increased stability can be extended to thermo-optical performance, with the Cz-TBA system showing higher color purity and stronger emission intensity within blue light wavelength than carbazole alone. Nevertheless, measurements of emitting spectral stability at a broader temperature range (100–200°C) and photoluminescence quantum yield suggested that there is a delicate trade-off between the performance and adamantane content.

Synthesis of Allahabadolactone A

A synthesis of allahabadolactone A is described employing diastereoselective Diels-Alder and selenocyclization reactions, starting from (R)-citronellal and propylene oxide. The Diels-Alder substrate is built up in an efficient manner by rhodium-catalyzed alkyne hydroboration and palladium-catalyzed coupling reactions of E-1,2-dichloroethene. It is observed that the Diels-Alder reaction only displays high diastereoselectivity when the diene bears an additional alkene substituent but not an alkyne substituent.

Catalyst Selection Facilitates the Use of Heterocyclic Sulfinates as General Nucleophilic Coupling Partners in Palladium-Catalyzed Coupling Reactions.

A range of 5- and 6-membered heterocycle-derived sulfinates are shown to be effective nucleophilic coupling partners with aryl chlorides and bromides using Pd(0) catalysis. The use of optimal reaction conditions, specifically incorporating a P(t-Bu)2Me-derived Pd catalyst, allowed reactions to be performed at moderate temperatures and enabled the inclusion of a variety of sensitive functional groups. Challenging heterocyclic sulfinates, including pyrazine, pyridazine, pyrimidine, pyrazole, and imidazole, were all shown to perform well.

Palladium-Catalyzed Decarboxylative Coupling of Alkynyl Carboxylic Acids and Alkenyl Tosylates for the Synthesis of Enynones.

A palladium-catalyzed decarboxylative coupling reaction was developed for the synthesis of 3-(1-alkynyl)-2-cyclohexen-1-ones. A variety of alkynyl carboxylic acids were coupled with 3-oxocyclohexenyl tosylates to afford the corresponding enynones in good to excellent yields. The developed catalytic system is phosphine free and showed good tolerance toward various functionalities such as chloride, cyano, nitro, ester, aldehyde, and alcohol groups. In addition, phenylpropiolic acid exhibited higher reactivity in the reaction with alkenyl toslyate than phenyl acetylene.