Pd-catalyzed Coupling Research Articles

Mechanism of copper-free Sonogashira reaction operates through palladium-palladium transmetallation

The seminal contributions by Sonogashira, Cassar and Heck in mid 1970s on Pd/Cu- and Pd-catalysed (copper-free) coupling of acetylenes with aryl or vinyl halides have evolved in myriad applications. Despite the enormous success both in academia and in industry, however, critical mechanistic questions of this cross-coupling process remain unresolved. In this study, experimental evidence and computational support is provided for the mechanism of copper-free Sonogashira cross-coupling reaction. In contrast to the consensus monometallic mechanism, the revealed pathway proceeds through a tandem Pd/Pd cycle linked via a multistep transmetallation process. This cycle is virtually identical to the Pd/Cu tandem mechanism of copper co-catalysed Sonogashira cross-couplings, but the role of CuI is played by a set of PdII species. Phosphine dissociation from the square-planar reactants to form transient three-coordinate Pd species initiates transmetallation and represents the rate-determining step of the process.

A Synthetic Methodology Toward Pyrrolo[2,3- b]pyridones for GC Base Pair Recognition.

Flexible synthetic access to a novel biarylic GC binding motif is presented, consisting of a pyridone connected to a fused pyrrolo[2,3- b]pyridone. Extensive molecular modeling led to an optimized design with perfect complementarity to the Hoogsteen site inside DNA's major groove. A wide range of functional elements can be introduced by minor modifications of the synthetic strategy. Our approach relies on mild Pd-catalyzed coupling reactions, featuring a triple heterohalogenated orthogonally addressable pyridine as a key intermediate.

Total Synthesis of (−)‐Cylindrocyclophane F: A Yardstick for Probing New Catalytic C−C Bond‐Forming Methodologies

A short and efficient total synthesis of the C2 -symmetric (-)-cylindrocyclophane F is presented, using a cross olefin metathesis dimerization strategy for construction of the [7,7]-paracyclophane macrocycle. The synthesis of the dimerization building block includes a Pd-catalyzed sp3 -sp2 Negishi cross coupling of a sterically hindered Zn-reagent with an aromatic triflate, an enantiospecific Zn-catalyzed sp3 -sp3 cross coupling of an α-hydroxy ester triflate with a Grignard reagent and the application of an enantioselective Rh-catalyzed C-allylation of an electron rich arene.

Effect and position of spiro-bipropylenedioxythiophene π-spacer in donor-π-spacer-acceptor dyes for dye-sensitized solar cell

Improper orientation and self-assembly of dyes on TiO2 surface are the main disadvantages at the dye-TiO2 interface that governs both charge injection and dye regeneration processes. In this report, a series of homo spiro-dimeric donor-π-spacer-acceptor (D-π-A) dyes based on bithiophene and terthiophene spacers with two-anchoring group containing dyes, TT1, T1T, TT1T were designed and synthesized by Pd-catalyzed successive Suzuki coupling followed by direct arylation reactions. The position of branching centre in TT1 and T1T was systematically varied, where the spiro unit was placed near and away from the anchoring carboxylic acid unit, respectively. The dimeric spiro-dye T1T showed device performance, which is 1.6 fold higher than its structural isomeric analogue TT1, of 3.9% with a Voc and Jsc of 0.593 V and 9.09 mA/cm2, respectively, whereas for the isomeric analogue TT1 a device performance of 2.45% (Voc of 0.568 V and Jsc of 6.25 mA/cm2) under simulated 1 Sun (100 mW/cm2) condition. The improved Voc for the dye T1T compared to TT1 dye was ascribed to the dipole moment exerted by the dyes on TiO2 surface. Further the PCE of 4.16% (Voc 0.589 V, Jsc 9.79 mA/cm2 respectively) maximum was observed, when an extra thiophene unit was inserted in between the donor and π-spacer in dye TT1T. The shifting the position of branching spiroBiProDOT π-spacer makes an impact on the device performance by synergistically enhancing both Voc and Jsc.

Carborane-BODIPY Dyads: New Photoluminescent Materials through an Efficient Heck Coupling.

A small library of carborane-BODIPY/aza-BODIPY dyads were efficiently synthesized by means of a novel convergent synthetic approach, the key step of which is a Pd-catalyzed Heck coupling reaction. The structural characterization and photoluminescence properties of the newly synthesized dyads were evaluated. The presence of the carborane did not significantly alter the photophysical patterns of the BODIPY or aza-BODIPY in the final fluorophores, but it produced a decrease of the emission fluorescent quantum yields that was in the range from 1.4 % for aza-BODIPY to 48 % for BODIPY-dyads. The carborane-BODIPY dyads were successfully incorporated into cells, especially compounds 2, 4 and 13, demonstrating their cytoplasmic localization. The fluorescent and biocompatibility properties make these compounds good candidates for in vitro cell tracking.

New Directions in Transition Metal Catalyzed Carbonylation Chemistry.

Carbon monoxide (CO) represents an important C1-building block for the construction of some of the most fundamental chemical functionalities carrying a carbon-oxygen double bond. Transition metal catalysis plays a key role in promoting such transformations. We have earlier shown that the combination of palladium catalysis with CO releasing molecules and the two-chamber reactor, COware, provides a convenient and safe means for performing traditional Pd-catalyzed carbonylative couplings, as well as being a platform for the discovery of new carbonylation reactions. Furthermore, the method can be adapted to 13C- and 14C-isotope labeling, as well as providing for a suitable setting for developing efficient carbonylation reactions with 11CO. Herein, we provide a short overview of our latest findings in this area with emphasis on carbonylative couplings with fluorinated building blocks, but also discuss our efforts to develop viable Ni-catalyzed carbonylations with aliphatic substrates, which can be performed efficiently under low CO partial pressures.

Selective arylation of phenol proteted propygyl bromide via pd-catalysed Suzuki coupling reaction: synthesis, mechanistic studies by DFT calculations and Their Pharmacological Aspects"

Biaryls are the potential source of synthetic drugs. The present study describes the synthesis of a series of functionalized biphenyl derivatives (3a-3g) using Pd-catalyzed Suzuki coupling reaction. The experimental results revealed the facile synthesis of biphenyl derivatives (3a-3g) with notably high yield (80-88%). Density functional theory (DFT) studies were performed by Gaussian 09 software in order to rationalize the selectivity of coupling at C-Br bond instead of C-Cl bond. In addition of synthesis, the biological activities (biofilm inhibition, hemolytic and anti-thrombolytic) of these novel compounds were investigated. These results exhibited good biofilm inhibition (5.86-65.8%), hemolytic (1.32-30.1%) and anti-thrombolytic activities (9.64-42.5%), indicating the potential use of these compounds for pharmaceutical applications

Palladium-catalyzed synthesis of 3-trifluoromethylated 1,3-dienes from acrylate derivatives and BTP

Here we reported a Pd-catalyzed coupling reaction between acrylate derivatives and BTP (2-bromo-3,3,3-trifluoropropene) to access 3-trifluoromethylated 1,3-dienes. The reaction allows the formation of the corresponding products in good to excellent yields and moderate Z/E diastereoisomeric ratios. This method broadens the current toolbox to access 3-trifluoromethylated 1,3-dienes.

Highly Efficient Coupling of Unstable Bicyclic Pyrimidines and Pyrazoles under Basic Conditions, and its Application to the Synthesis of Pharmaceutical Compounds

The efficient Pd-catalyzed coupling of unstable bicyclic pyrimidines and pyrazoles under basic conditions was established for the first time. The reactions proceeded with excellent yields without hydrolysis using Pd2(dba)3, t BuXPhos, and K3PO4.

Regio- and Stereoselective Allylindation of Alkynes Using InBr₃ and Allylic Silanes: Synthesis, Characterization, and Application of 1,4-Dienylindiums toward Skipped Dienes.

Regioselective anti-allylindation of alkynes was achieved using InBr3 and allylic silanes. Various types of alkynes and allylic silanes were applicable to the present allylindation. This sequential process used the generated 1,4-dienylindiums to establish novel synthetic methods for skipped dienes. The 1,4-dienylindiums were characterized by spectral analysis and treated with I2 to stereoselectively give 1-iodo-1,4-dienes. The Pd-catalyzed cross coupling of 1,4-dienylindium with iodobenzene successfully proceeded in a one-pot manner to afford the corresponding 1-aryl-1,4-diene.

Synthesis and Pd-catalyzed coupling of1-C-stannylated glycals

1-Tributylstannyl glycals were applied as versatile tools in the Pd(0)-mediated synthesis of glycal phthalonitrile conjugates. Likewise, selective homo-coupling of 1-tributylstannyl glycals furnishing C1-C1’ linked glycal dimers was investigated by using Pd(II)-species. For both Stille type couplings the rate-accelerating effect of copper(I) thiophene-2-carboxylate (CuTC) was exploited. The synthesis of stannylated glycal precursors was significantly improved by establishing a one-pot two-step procedure via glycosyl sulfoxides.

Sequential Pd(0)/Fe(III) Catalyzed Azide-Isocyanide Coupling/Cyclization Reaction: One-Pot Synthesis of Aminotetrazoles.

A rapid and efficient synthesis of aminotetrazole from aryl azides, isocyanides, and TMSN3 is developed. The reaction is promoted by sequential Pd(0)/Fe(III) catalysis. The reaction sequence utilizes the Pd-catalyzed azide-isocyanide denitrogenative coupling reaction to generate unsymmetric carbodiimide in situ, which reacts with TMSN3 in the presence of FeCl3 in a single pot. The methodology has distinct advantages over traditional synthetic approaches where toxic Hg and Pb salts are employed at stoichiometric scale.

Syntheses of Dithienoarsole-containing Polymers via Suzuki-Miyaura and Sonogashira-Hagihara Coupling Reactions

Main chain type dithienoarsole (DTA) polymers were synthesized by two kinds of optimized Pd-catalyzed coupling reactions. X-ray fluorescence spectroscopy revealed that there was no residual metal in the obtained polymers, meaning that lone pairs of the DTA polymers were free from coordination. The emission color was widely tuned by the π-conjugated comonomers. Furthermore, the modification of the DTA polymer was carried out via complexation with gold(I) chloride.

Synthesis and Optoelectronic Properties of Block and Random Copolymers Containing Pendant Carbazole and (Di)phenylanthracene.

Synthesis of novel block and random copolymers, containing a carbazole unit and (di)phenylanthracene moiety in the side chains, has been described in this paper. Block and random copolymers composed of 4-bromophenyl vinyl sulfide (BPVS) and N-vinylcarbazole (NVC) were initially prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization. Then, anthracene-based groups were introduced on the bromophenyl unit in the carbazole-containing copolymers by Pd-catalyzed coupling to yield functional copolymers with additional (di)phenylanthracene units. The resulting copolymers, having two distinct electronic functionalities, exhibited characteristic fluorescence resonance energy transfer, as confirmed by UV-vis and fluorescence spectra.

Modular ipso/ ortho Difunctionalization of Aryl Bromides via Palladium/Norbornene Cooperative Catalysis.

Palladium/norbornene (Pd/NBE) cooperative catalysis has emerged as a useful tool for preparing poly substituted arenes; however, its substrate scope has been largely restricted to aryl iodides. While aryl bromides are considered as standard substrates for Pd-catalyzed cross coupling reactions, their use in Pd/NBE catalysis remains elusive. Here we describe the development of general approaches for aryl bromide-mediated Pd/NBE cooperative catalysis. Through careful tuning the phosphine ligands and quenching nucleophiles, ortho amination, acylation and alkylation of aryl bromides have been realized in good efficiency. Importantly, various heteroarene substrates also work well and a wide range of functional groups are tolerated. In addition, the utility of these methods has been demonstrated in sequential cross coupling/ ortho functionalization reactions, consecutive Pd/NBE-catalyzed difunctionalization to construct penta-substituted aromatics and two-step meta functionalization reactions. Moreover, the origin of the ligand effect in ortho amination reactions has been explored through DFT studies. It is expected that this effort would significantly expand the reaction scope and enhance the synthetic potential for Pd/NBE catalysis in preparing complex aromatic compounds.

Synthesis of Thiophene-Based π-Conjugated Oligomers via Ligand-Enabled Pd-Catalyzed Suzuki-Miyaura Coupling of Haloterthienyls.

A ligand-enabled Pd-catalyzed Suzuki-Miyaura coupling of haloterthienyls for the synthesis of various thiophene-based π-conjugated oligomers including quinquethiophenes is demonstrated. An indolyl phosphine ligand plays an important role in this transformation. Thiopheneboronic acids were well applied, which might open up a window for the application of thiopheneboronic acids in the synthesis of thiophene-based π-conjugated oligomers in materials chemistry.

Pd-Catalyzed Alkene Diamination Reactions of Nitrogen Electrophiles: Synthesis of Cyclic Guanidines and Ureas Bearing Dialkylaminomethyl Groups.

The Pd-catalyzed coupling of N-allylguanidines or N-allylureas with O-benzoylhydroxylamine derivatives affords cyclic guanidines or cyclic ureas bearing dialkylaminomethyl groups. The desired products are obtained in good yield, and substrates bearing substituents at the allylic position are transformed with moderate diastereoselectivity. The mechanism of these reactions appears to involve anti-aminopalladation of the alkene, followed by a rare sp3C-sp3N bond-forming reductive elimination from an alkylpalladium complex that contains β-hydrogen atoms.

Red thermally activated delayed fluorescence polymers containing 9H-thioxanthen-9-one-10,10-dioxide acceptor group as pendant or incorporated in backbone

Abstract A set of conjugated polymers PCzDPTx with carbazole/diphenylamine as backbone and 9H-thioxanthen-9-one-10,10-dioxide as the pendant, where DPT is 2-(4-(diphenylamino)-phenyl)-9H-thioxanthen-9-one-10,10-dioxide, and x = 1, 5, 10, 25 and 50, respectively, and two alternating copolymers PTCz and PTD with the backbone consisting of the acceptor unit 9H-thioxanthen-9-one-10,10-dioxide and the donor unit carbazole and diphenylamine groups have been respectively synthesized by Pd-catalyzed Suzuki coupling polycondensation. These polymers in films show long wavelength emissions of 573–629 nm with thermally activated delayed fluorescence (TADF) characteristics, confirmed by theory calculations and their transient PL decay spectra. Various organic light-emitting diodes (OLEDs) using the TADF polymers as emitters were fabricated by solution processing. The doped OLEDs based on the polymers PTD and PCzDPT50 with the 50% molar content of the DPT unit as the emitters produce the saturated red electroluminescence with Commission Internationale de l'Eclairage (CIE) coordinates (0.64, 0.36) and (0.63, 0.37), respectively. For the first time, a TADF polymer based sensitizer was utilized to further improve the electroluminescent performances of the TADF polymers with low quantum yields, e.g., at the maximum, 3.8-fold increase in the brightness and 1.8-fold increase in the external quantum efficiency were simultaneously demonstrated.

Direct Synthesis of Chalcones from Anilides with Phenyl Vinyl Ketones by Oxidative Coupling Through C-H Bond Activation.

A novel approach for synthesizing chalcones by Pd-catalyzed oxidative coupling is described. This is the first report of the efficient coupling reaction of acetanilides with phenyl vinyl ketones under mild conditions. Selective C–H activation occurred next to the acetamide group to afford 2-aminochalcone derivatives. The reaction proceeded under an O2 atmosphere without any chemical co-oxidants.

Polymer Constructed Through the Formation of Carbon-Carbon Triple Bonds: Reductive Coupling Polymerization of Bis(benzylic gem-tribromide)s.

Ethynylene-bridged polymers are currently synthesized by alkyne metathesis polymerization or Pd-catalyzed coupling between diethynylarene and dihaloarene. We report the formation of C≡C linkages in reductive coupling polymerization of bis(benzylic gem-tribromide)s promoted by Cu/polyamine under mild conditions. The polymer backbone was constructed through cascade formation of (Br)C═C(Br) bonds and C≡C bonds. This protocol provides a new method for synthesis of ethynylene-bridged polymers using monomers without alkynyl groups.