Stille Coupling Research Articles

A palladium(0)-threonine complex immobilized on the surface of magnetic mesocellular foam: an efficient, stable, and magnetically separable nanocatalyst for Suzuki, Stille, and Heck cross-coupling reactions.

In this study, a new palladium nanocatalyst was supported on l-threonine functionalized magnetic mesocellular silica foams (MMCF@Thr-Pd) and was characterized by FT-IR, XRD, BET, SEM, EDS, VSM, TGA, ICP-OES and elemental mapping techniques. The obtained MMCF@Thr-Pd performance can show excellent catalytic activity for Stille, Suzuki, and Heck coupling reactions, and the corresponding products were obtained with high yields. More importantly, the efficient and stable MMCF@Thr-Pd nanocatalyst was recovered by applying an external magnetic field and reused for at least five consecutive runs without a change in the catalytic activity.

Asymmetric total synthesis of (+)-propolisbenzofuran B.

The first asymmetric total synthesis of (+)-propolisbenzofuran B is accomplished in 11 steps with an overall yield of 11.9%. The key steps are tandem deacetylative Sonogashira coupling-annulation reaction to synthesize the 2-substituted benzofuran core, stereoselective syn-aldol reaction and Friedel-Crafts cyclization to install the desired stereocenters & third-ring, and Stille coupling for C-acetylation.

Bulky, electron-rich, renewable: analogues of Beller's phosphine for cross-couplings.

In recent years, considerable progress has been made in the conversion of biomass into renewable chemicals, yet the range of value-added products that can be formed from biomass remains relatively small. Herein, we demonstrate that molecules available from biomass serve as viable starting materials for the synthesis of phosphine ligands, which can be used in homogeneous catalysis. Specifically, we prepared renewable analogues of Beller's ligand (di(1-adamantyl)-n-butylphosphine, cataCXium® A), which is widely used in homogeneous catalysis. Our new renewable phosphine ligands facilitate Pd-catalysed Suzuki-Miyaura, Stille, and Buchwald-Hartwig coupling reactions with high yields, and our catalytic results can be rationalized based on the stereoelectronic properties of the ligands. The new phosphine ligands generate catalytic systems that can be applied for the late-stage functionalization of commercial drugs.

3D printing of a palladium-alumina cermet monolithic catalyst: catalytic evaluation in microwave-assisted cross-coupling reactions

A straightforward manufacture strategy is proposed to obtain an efficient and robust palladium-alumina (Pd0/Al2O3) cermet monolithic catalyst, specifically designed to perform safe microwave assisted organic synthesis (MAOS). In this approach, a cermet catalyst with high surface area, controlled composition and adapted shape and dimensions to a microwave reactor vessel is generated via 3D printing technology and sintering. The resulting catalyst has been explored in heterogeneous Suzuki, Sonogashira, Stille and Heck cross-coupling reactions, in MAOS. The Pd0 catalyst is permanently active, stable, without leaching and can be recycled and reused at least 200 reaction cycles. The generation of hot spots, sparking or hazardous discharges is controlled by the effective immobilization of the palladium in the monolithic structure during the reaction. The palladium content is forming part of both the internal and external structure, providing greater mechanical resistance and catalytic activity with respect to the basic ceramic material (alumina).

A fruitful century for the scalable synthesis and reactions of biphenyl derivatives: applications and biological aspects.

This review provides recent developments in the current status and latest synthetic methodologies of biphenyl derivatives. Furthermore, this review investigates detailed discussions of several metalated chemical reactions related to biphenyl scaffolds such as Wurtz-Fittig, Ullmann, Bennett-Turner, Negishi, Kumada, Stille, Suzuki-Miyaura, Friedel-Crafts, cyanation, amination, and various electrophilic substitution reactions supported by their mechanistic pathways. Furthermore, the preconditions required for the existence of axial chirality in biaryl compounds are discussed. Furthermore, atropisomerism as a type of axial chirality in biphenyl molecules is discussed. Additionally, this review covers a wide range of biological and medicinal applications of the synthesized compounds involving patented approaches in the last decade corresponding to investigating the crucial role of the biphenyl structures in APIs.

A Mini Review on the Development of Conjugated Polymers: Steps towards the Commercialization of Organic Solar Cells

This review article covers the synthesis and design of conjugated polymers for carefully adjusting energy levels and energy band gap (EBG) to achieve the desired photovoltaic performance. The formation of bonds and the delocalization of electrons over conjugated chains are both explained by the molecular orbital theory (MOT). The intrinsic characteristics that classify conjugated polymers as semiconducting materials come from the EBG of organic molecules. A quinoid mesomeric structure (D-A ↔ D+ = A-) forms across the major backbones of the polymer as a result of alternating donor-acceptor segments contributing to the pull-push driving force between neighboring units, resulting in a smaller optical EBG. Furthermore, one of the most crucial factors in achieving excellent performance of the polymer is improving the morphology of the active layer. In order to improve exciton diffusion, dissociation, and charge transport, the nanoscale morphology ensures nanometer phase separation between donor and acceptor components in the active layer. It was demonstrated that because of the exciton's short lifetime, only small diffusion distances (10-20 nm) are needed for all photo-generated excitons to reach the interfacial region where they can separate into free charge carriers. There is a comprehensive explanation of the architecture of organic solar cells using single layer, bilayer, and bulk heterojunction (BHJ) devices. The short circuit current density (Jsc), open circuit voltage (Voc), and fill factor (FF) all have a significant impact on the performance of organic solar cells (OSCs). Since the BHJ concept was first proposed, significant advancement and quick configuration development of these devices have been accomplished. Due to their ability to combine great optical and electronic properties with strong thermal and chemical stability, conjugated polymers are unique semiconducting materials that are used in a wide range of applications. According to the fundamental operating theories of OSCs, unlike inorganic semiconductors such as silicon solar cells, organic photovoltaic devices are unable to produce free carrier charges (holes and electrons). To overcome the Coulombic attraction and separate the excitons into free charges in the interfacial region, organic semiconductors require an additional thermodynamic driving force. From the molecular engineering of conjugated polymers, it was discovered that the most crucial obstacles to achieving the most desirable properties are the design and synthesis of conjugated polymers toward optimal p-type materials. Along with plastic solar cells (PSCs), these materials have extended to a number of different applications such as light-emitting diodes (LEDs) and field-effect transistors (FETs). Additionally, the topics of fluorene and carbazole as donor units in conjugated polymers are covered. The Stille, Suzuki, and Sonogashira coupling reactions widely used to synthesize alternating D-A copolymers are also presented. Moreover, conjugated polymers based on anthracene that can be used in solar cells are covered.

Enantioselective Total Synthesis of (+)-Alterbrassicicene C.

Herein, the first total synthesis of (+)-alterbrassicicene C (2) is described. Key features of the synthesis include an oxiranium mediated ether ring expansion, an oxa-Michael/retro-oxa-Michael cascade, and installation of a vinyl methoxy ether moiety via Stille coupling.

Synthese und Biologische Untersuchungen von C(13)/C(13′)‐Bis(desmethyl)disorazol Z**

AbstractWir beschreiben hier die Totalsynthese des Makrodiolids C(13)/C(13′)‐Bis(desmethyl)disorazol Z über die Bildung des Makrozyklus durch eine doppelte inter‐/intramolekulare Stille‐Kreuzkupplung eines monomeren Vinylstannan/Vinyliodid Vorläufers. Der Schlüsselschritt in der Synthese dieses Vorläufers ist die stereoselektive Aldolreaktion eines formalen Evans Acetat‐Aldolprodukts mit Crotonaldehyd. Wie mitttels Röntgenkristallographie gezeigt werden konnte, ist der Bindungsmodus des C(13)/C(13′)‐Bis(desmethyl)disorazol Z an Tubulin praktisch identisch mit demjenigen des Naturstoffs Disorazol Z. Desgleichen unterdrückt das C(13)/C(13′)‐Bis(desmethyl)disorazol Z die Tubulinpolymerisation zumindest gleich stark wie das Disorazol Z und es hemmt das Zellwachstum offenbar sogar mit höherer Potenz.

Synthesis and Biological Evaluation of C(13)/C(13')-Bis(desmethyl)disorazole Z.

We describe the total synthesis of the macrodiolide C(13)/C(13')-bis(desmethyl)disorazole Z through double inter-/intramolecular Stille cross-coupling of a monomeric vinyl stannane/vinyl iodide precursor to form the macrocycle. The key step in the synthesis of this precursor was a stereoselective aldol reaction of a formal Evans acetate aldol product with crotonaldehyde. As demonstrated by X-ray crystallography, the binding mode of C(13)/C(13')-bis(desmethyl)disorazole Z to tubulin is virtually identical with that of the natural product disorazole Z. Likewise, C(13)/C(13')-bis(desmethyl)disorazole Z inhibits tubulin assembly with at least the same potency as disorazole Z and it appears to be a more potent cell growth inhibitor.

Synthesis of thieno[3,4-c] pyrrole-4,6-dione-based small molecules for application in organic thin-film transistors

The synthesis of two alternating donor-acceptor (D-A) small molecules revolving around thieno[3,4-c]pyrrole-4,6-dione (TPD) as the main acceptor building block is reported herein. The materials are synthesized using a robust Stille coupling to attach the TPD core with thiophene donors on either of its side, and completed with an aldol condensation under mild conditions for the addition of terminal secondary acceptor building blocks, representing a sought out A2-D-A1-D-A2 structure. The two newly synthesized materials are set to be used as organic semiconductors in organic thin-film transistor (OTFT) devices. Comparative optical, computational, and electrochemical studies were carried out on these new materials to investigate their ability to act as potential n-type organic semiconductors. The materials were then incorporated into bottom-gate bottom-contact OTFT devices, and subsequent thin-film engineering studies were done to probe the effects that solvent and post-deposition annealing conditions had on device performance. From these conditions, the rhodanine-derived D-A material exhibited the greatest electron field-effect mobility (0.011 cm2 V−1 s−1), and a threshold voltage of 20.1 V under vacuum.

Radiochemical Synthesis and Evaluation of 3-[11C]Methyl-4-aminopyridine in Rodents and Nonhuman Primates for Imaging Potassium Channels in the CNS.

Demyelination, the loss of the insulating sheath of neurons, causes failed or slowed neuronal conduction and contributes to the neurological symptoms in multiple sclerosis, traumatic brain and spinal cord injuries, stroke, and dementia. In demyelinated neurons, the axonal potassium channels Kv1.1 and Kv1.2, generally under the myelin sheath, become exposed and upregulated. Therefore, imaging these channels using positron emission tomography can provide valuable information for disease diagnosis and monitoring. Here, we describe a novel tracer for Kv1 channels, [11C]3-methyl-4-aminopyridine ([11C]3Me4AP). [11C]3Me4AP was efficiently synthesized via Pd(0)-Cu(I) comediated Stille cross-coupling of a stannyl precursor containing a free amino group. Evaluation of its imaging properties in rats and nonhuman primates showed that [11C]3Me4AP has a moderate brain permeability and slow kinetics. Additional evaluation in monkeys showed that the tracer is metabolically stable and that a one-tissue compartment model can accurately model the regional brain time-activity curves. Compared to the related tracers [18F]3-fluoro-4-aminopyridine ([18F]3F4AP) and [11C]3-methoxy-4-aminopyridine ([11C]3MeO4AP), [11C]3Me4AP shows lower initial brain uptake, which indicates reduced permeability to the blood-brain barrier and slower kinetics, suggesting higher binding affinity consistent with in vitro studies. While the slow kinetics and strong binding affinity resulted in a tracer with less favorable properties for imaging the brain than its predecessors, these properties may make 3Me4AP useful as a therapeutic.

Pd-Catalyzed Arylation of Secondary α-Alkoxytricyclohexylstannanes.

We have developed a general process for the formation of α-arylethers via the Pd-catalyzed arylation of secondary α-alkoxytricyclohexylstannanes. Incorporation of cyclohexyl spectator ligands into the alkylstannane and the use of the electron-deficient ligand JackiePhos (1) are critical for achieving selective alkyl transfer in this process. This system circumvents the need for a coordinating/directing oxygen-protecting group to promote selective alkyl transfer and enables α-tetrahydropyran, α-tetrahydrofuran, and open-chain secondary α-alkoxy groups to be employed efficiently in Pd-catalyzed Stille reactions with a broad range of aryl electrophiles. These findings suggest that selective transmetalation of a single marginally activated secondary alkyl unit from Sn to Pd should be broadly achievable provided that unactivated secondary alkyl ligands comprise the other three groups of the tetraalkylstannane.

Conjugated Polymers Containing EDOT Units as Novel Materials for Electrochromic and Resistance Memory Devices.

Four new multifunctional polymers (P1, P2, P3, and P4) containing EDOT units were synthesized by the Stille coupling reaction. A PL spectrum test found that the introduction of large conjugated groups led to strong fluorescence emission in all polymers. Among the electrochromic and switch properties, these polymer films exhibited reversible color changes, as well as good coloring efficiency. Electrochemical experiments found that the initial oxidation potentials of the polymers were 1.27 V, 1.67 V, 1.78 V, and 1.58 V, respectively. Among them, P3 showed a higher coloring efficiency (283.3 cm2·C-1), and P2 showed a shorter response time (tc = 2.2 s, tb = 2.8 s). These polymers all exhibited electrochromic and resistive switching storage characteristics. They have good solubility in many organic solvents. In the resistance switch memory characteristics, all polymers had obvious memristive properties, and P4 exhibited a larger switch current ratio (2527.42) and a smaller threshold voltage (0.9 V).

Efficient Synthesis of 4,8-Dibromo Derivative of Strong Electron-Deficient Benzo[1,2-d:4,5-d']bis([1,2,3]thiadiazole) and Its SNAr and Cross-Coupling Reactions.

An efficient synthesis of hydrolytically and thermally stable 4,8-dibromobenzo[1,2-d:4,5-d']bis([1,2,3]thiadiazole) by the bromination of its parent heterocycle is reported. The structure of 4,8-dibromobenzo[1,2-d:4,5-d']bis([1,2,3]thiadiazole) was confirmed by X-ray analysis. The conditions for the selective aromatic nucleophilic substitution of one bromine atom in this heterocyclic system by nitrogen nucleophiles are found, whereas thiols formed the bis-derivatives only. Suzuki-Miyaura cross-coupling reactions were found to be an effective method for the selective formation of various mono- and di(het)arylated derivatives of strong electron-deficient benzo[1,2-d:4,5-d']bis([1,2,3]thiadiazole), and Stille coupling can be employed for the preparation of bis-arylated heterocycles, which can be considered as useful building blocks for the synthesis of DSSCs and OLEDs components.

Total Synthesis of Loroxanthin

The first total synthesis of loroxanthin (1) was accomplished by Horner-Wadsworth-Emmons reaction of C25-apocarotenal 8 having a silyl-protected 19-hydroxy moiety with C15-phosphonate 25 bearing a silyl-protected 3-hydroxy-ε-end group. Preparation of apocarotenal 8 was achieved via Stille coupling reaction of alkenyl iodide 10 with alkenyl stananne 9, whereas phosphonate 25 was prepared through treatment of ally alcohol 23 with triethyl phosphite and ZnI2. The ally alcohol 23 was derived from the known (3R,6R)-3-hydroxy C15-aldehyde 20, which was obtained by direct optical resolution of racemate 20 using a semi-preparative chiral HPLC column.

Impact of fluorination of central thiophene linking core in thermostable perylene-diimide-based dimeric acceptors on molecular configuration and photovoltaic performance

Fluorination was an easy and effective strategy to adjust the absorption, electronic energy level, molecular configuration and aggregation as well as charge mobility, miscibility, morphology and photovoltaic property. Herein, two perylene-diimide-based non-fullerene dimeric acceptors, called T-(PDI-HD)2 and 2FT-(PDI-HD)2, were obtained via Stille coupling reaction between bistin compounds (TSn and 2FTSn) and monobromide PDI-HDBr. The dramatically reduced twisted angle from 81.80o to 19.78o and strengthened molecular stacking both in chlorobenzene solution and solid film states were found after fluorination, resulting in an elevated thermostability and slightly enhanced electron mobility. Furthermore, fluorination led to the down-shifted ELUMO, worse miscibility and undesired microstructural morphology with oversized aggregation which impeded the exciton dissociation and restricted the photocurrent. As a consequence, the slightly declined VOC, 18.52% down-shifted JSC but 12.38% increased FF were found, leading to a 9.69% decline in PCE from 2.58% to 2.33% after bisfluorinating the central thiophene linking core, which was imputed to the deepened ELUMO, worse light-harvesting capability and undesired morphology as a result of fluorination regardless of the slightly elevated electron mobility. Our results have demonstrated that it was cautious that incorporating fluorine substituents into central linking core by virtue of tuning the twisting degree boosted the photovoltaic property in PDI-based dimeric acceptors.

Synthesis of Novel Key Chromophoric Intermediates via C-C Coupling Reactions

The fundamentals of Pd-catalyzed Csp2−Csp2 Miyaura borylation, Suzuki cross-coupling, and Stille cross-coupling reactions for a variety of borylated precursors based on phenothiazine (PTZ), phenoxazine (POZ), carbazole (Cz), and quinoxaline (QX) units have been explored. Three palladium-based catalysts were chosen for this study: Pd(PPh3)4, Pd(PPh3)2Cl2, and Pd(dppf)Cl2, applying different reaction conditions. Around 16 desired chromophores were successfully designed and synthesized using C-C cross-coupling reactions in moderate to excellent yields, including PTZ, POZ, and Cz units coupled with QX, indolinium iodide, thienyl, phenyl, or triphenylamine moieties. Additionally, PTZ, POZ, and Cz have been employed in synthesizing various pinacol boronate ester derivatives in good to moderate yields. Interestingly, Pd(dppf)Cl2 was found to be the best catalyst for borylation, and C-C cross-coupling reactions occurred in as little as 30 min, with an excellent yield exceeding 98%. Pd(PPh3)4 and Pd(PPh3)2Cl2 catalyzed the reaction to obtain the desired products in moderate to good yields after a long time (20–24 h). On the other hand, the Suzuki-Miyaura cross-coupling between N-(2-methyl)hexyl carbazole pinacol boronate ester derivative 10c and three halogenated quinoxaline derivatives—4-(3-(5-bromothiophen-2-yl)quinoxalin-2-yl)benzaldehyde (27), 4-(5-(3-(5-bromothiophen-2-yl)quinoxalin-2-yl)thiophen-2-yl)benzaldehyde (30), and 4-(3-chloroquinoxalin-2-yl)benzaldehyde (25) catalyzed by Pd(PPh3)4—afforded three carbazole-quinoxaline chromophores (28, 30, and 31, respectively) in 2–3 h, with good to excellent yields reaching 86%. The electron-deficient QX couplers proved to be coupled efficiently using the Stille coupling reaction, which involves the coupling between electron-rich orgaostannane and electron-deficient halide. The synthesized precursors and desired chromophores were characterized by FTIR, 1H-NMR, 13C-NMR, and HRMS.

Stretchable diketopyrrolopyrrole-based conjugated polymers with asymmetric sidechain designs for field-effect transistor applications

BackgroundThe asymmetric sidechain design has been recently proposed as a potential strategy to improve the mobility-stretchability property of conjugated polymers. In this study, the influences of the asymmetric sidechain designs on the mobility-stretchability properties of DPP-based conjugated polymers are investigated. Three asymmetric sidechain combinations based on a linear alkyl chain (C12), a carbosilane chain (Si), and a siloxane-terminated chain (SiO) are designed to synthesize three polymers, P(SiO-C12), P(Si-C12), and P(SiO-Si). MethodsAll polymers are synthesized via Stille coupling in a microwave reactor. Their basic properties including size exclusion chromatography (SEC), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC) are analyzed. Their optical and electrochemical properties are characterized using UV-vis absorption and cyclic voltammetry (CV). The morphology of the polymer films is analyzed through optical microscopy (OM), atomic force microscopy (AFM), and grazing-incidence X-ray diffraction (GIXD). Lastly, the transistor characteristics are measured using a Keithley 4200-SCS semiconductor parameter analyzer (Keithley Instruments Inc.) inside a N2-filled glove box. Significant findingsThe asymmetric SiO/Si sidechain combination enables P(SiO-Si) possess the highest degree of bimodal packing orientation because their branched geometries impose a large steric hindrance to disrupt the chain packing. As benefitting from such bimodal packing orientation, P(SiO-Si) is shown to deliver the highest hole mobility value and the best mobility-stretchability property among these three polymers. It can persist 56.7% of the initial μh value after 800 cycles of 60% strain while P(SiO-C12) and P(Si-C12) can only maintain 2.4% and 4.1% of the initial value. Our results clearly highlight the advantage of the asymmetric SiO/Si sidechain combination on improving the mobility-stretchability property of the derived polymer.

Improving Photocatalytic Stille Coupling Reaction by CuPd Alloy-Doped Ordered Mesoporous TiO2

Rational surface engineering of noble metal-doped photocatalysts is essential for the efficient conversion of solar energy into chemical energy, but it is still challenging to perform. Herein, we reported an effective strategy for structuring alloyed CuPd (CP) nanoclusters on the ordered mesoporous TiO2 (CPT) by a pore confinement effect. The resultant CPT exhibited an extraordinary photocatalytic activity during Stille reaction under visible light. The X-ray photoelectron spectroscopy spectra, the field emission scanning electron microscope (FESEM) images, and the aberration-corrected high-angle annular dark scanning transmission electron microscopy (HAADF-STEM) images demonstrated that CP nanoclusters were anchored in the mesoporous pore wall of TiO2, and the atomic ratio as well as densities of CP could be precisely modulated via the coordination configuration. As the atomic ratio of CP to TiO2 increased to a certain extent, their photocatalytic activity during Stille reaction increased. A mechanistic investigation suggested that the CP alloy could absorb visible light and its conduction electrons gained energy, which were available at the surface Pd sites. This allowed the Pd sites to become electron-rich and to accelerate the rate-determining step of the Stille reaction. As a result, the efficiency of the photocatalytic Stille coupling reaction was extraordinary enhanced.

Synthetic Studies on Amphidinolide F: Exploration of Macrocycle Construction by Intramolecular Stille Coupling.

Exploration of an ambitious new strategy for the total synthesis of the cytotoxic marine natural product amphidinolide F is described, which features fabrication of the core structure from four readily accessible fragments and macrocycle construction through C9–C10 bond formation by intramolecular Stille coupling between an alkenyl iodide and alkenyl stannane. Efficient stereoselective synthesis of each of the four building-blocks and subsequent coupling of them to produce the requisite cyclization precursor has been accomplished, but suitable conditions for high-yielding palladium-mediated closure of the macrocycle to produce the fully protected amphidinolide F ring system have yet to be identified.