Pd-catalyzed Cross-coupling Reactions Research Articles

Scalable Negishi Coupling between Organozinc Compounds and (Hetero)Aryl Bromides under Aerobic Conditions when using Bulk Water or Deep Eutectic Solvents with no Additional Ligands.

Pd-catalyzed Negishi cross-coupling reactions between organozinc compounds and (hetero)aryl bromides have been reported when using bulk water as the reaction medium in the presence of NaCl or the biodegradable choline chloride/urea eutectic mixture. Both C(sp3 )-C(sp2 ) and C(sp2 )-C(sp2 ) couplings have been found to proceed smoothly, with high chemoselectivity, under mild conditions (room temperature or 60 °C) in air, and in competition with protonolysis. Additional benefits include very short reaction times (20 s), good to excellent yields (up to 98 %), wide substrate scope, and the tolerance of a variety of functional groups. The proposed novel protocol is scalable, and the practicability of the method is further highlighted by an easy recycling of both the catalyst and the eutectic mixture or water.

Macrocyclic Arenes-Based Conjugated Macrocycle Polymers for Highly Selective CO2 Capture and Iodine Adsorption.

Incorporating synthetic macrocycles with unique structures and distinct conformations into conjugated macrocycle polymers (CMPs) can endow the resulting materials with great potentials in gas uptake and pollutant adsorption. Here, four CMPs (CMP-n, n=1-4) capable of reversibly capturing iodine and efficiently separating carbon dioxide are constructed from per-triflate functionalized leaning tower[6]arene (LT6-OTf) and [2]biphenyl-extended pillar[6]arene (BpP6-OTf) via Pd-catalyzed Sonogashira-Hagihara cross-coupling reaction. Intriguingly, owing to the appropriate cavity size of LT6-OTf and the numerous aromatic rings in the framework, the newly designed CMP-4 possesses an outstanding I2 affinity with a large uptake capacity of 208 wt % in vapor and a great removal efficiency of 94 % in aqueous solutions. To our surprise, with no capacity to accommodate nitrogen, CMP-2 constructed from BpP6-OTf is able to specifically capture carbon dioxide at ambient conditions.

Base-Free Cross-Couplings of Aryl Diazonium Salts in Methanol: PdII -Alkoxy as Reactivity-Controlling Intermediate.

Pd-catalyzed cross-coupling reactions of aryl diazonium salts are generally assumed to proceed via cationic PdII intermediates which in turn would be highly reactive in the subsequent transmetalation step. Contrary to this belief, we herein report our observation and rationalization of opposing reactivities of ArN2+ in Suzuki (=effective) and Stille (=ineffective) cross-couplings in MeOH. Our systematic experimental and computational studies on the roles of transmetalating agent, solvent, base and the likely involvement of in situ formed diazoether derivatives challenge the currently accepted mechanism. Our data suggest that the observed solvent dichotomy is primarily due to PdII -methoxy intermediates being formed, which are unreactive with arylstannanes, but highly reactive with arylboronic acids, complementing the Suzuki "Pd-oxy" mechanism with the direct demonstration of transmetalation of a PdII -alkoxy complex. Lewis acids were found to circumvent this reactivity divergence, promoting efficient couplings regardless of the employed conditions or coupling partners.

Blueish-white-light-emitting Nanographenes Developed by Pd-catalyzed Suzuki-Miyaura Cross Coupling Reactions

Abstract Top-down methods produce nanographenes with many carboxy groups on their edges. These functional groups can be utilized for developing multichromophoric systems. As proof of concept, pyrene is installed on the edges by Pd-catalyzed cross-coupling reactions. The lack of monomer emissions from the functionalized nanographenes indicates that the neighboring chromophores are sufficiently distant to form the excimer. The pyrene-installed nanographene emits bluish-white-light. Its lipophilic nature allows fabricating a nanographene-dispersed polymethyl methacrylate film emitting visible light.

Germatranes and carbagermatranes: (hetero)aryl and alkyl coupling partners in Pd-catalyzed cross-coupling reactions.

In the past few decades, palladium-catalyzed cross-coupling reactions have taken root in the construction of a complex synthetic community. The development of organometallics has been an important objective in this field. Our group has focused on exploiting new germanium-based reagents and the corresponding catalytic processes. In the past three years, we have established new methods for the synthesis of structure-modified (hetero)aryl germatranes and alkyl carbagermatranes. Particularly for alkyl carbagermatranes, the stability to be compatible with various derivatization reactions and the high activity for transmetallation (e.g. base/additive-free for primary alkyl carbagermatranes) distinguish them from many reported nucleophiles. In this article, we would introduce (1) the development process of organogermanium reagents in palladium-catalyzed cross-couplings; (2) the history of germatrane-type systems and the breakthrough we have made in the field; (3) the outlook for (carba)germatranes and alkyl-GeMe3.

A modular approach to mechanically gated photoswitching with color-tunable molecular force probes.

Molecular force probes conveniently report on mechanical stress and/or strain in polymers through straightforward visual cues. Unlike conventional mechanochromic mechanophores, the mechanically gated photoswitching strategy decouples mechanochemical activation from the ultimate chromogenic response, enabling the mechanical history of a material to be recorded and read on-demand using light. Here we report a completely redesigned, highly modular mechanophore platform for mechanically gated photoswitching that offers a robust, accessible synthesis and late stage diversification through Pd-catalyzed cross-coupling reactions to precisely tune the photophysical properties of the masked diarylethene (DAE) photoswitch. Using solution-phase ultrasonication, the reactivity of a small library of functionally diverse mechanophores is demonstrated to be exceptionally selective, producing a chromogenic response under UV irradiation only after mechanochemical activation, revealing colored DAE isomers with absorption spectra that span the visible region of the electromagnetic spectrum. Notably, mechanically gated photoswitching is successfully translated to solid polymeric materials for the first time, demonstrating the potential of the masked diarylethene mechanophore for a variety of applications in force-responsive polymeric materials.

Synthesis of bicyclic vinyl triazenes by Ficini-type reactions.

Cyclic olefins with triazene functions can display interesting reactivity, but synthetic access to these compounds is limited thus far. Herein, we describe the synthesis of cyclobutenyl triazenes fused to cyclopentanone or cyclohexanone rings. The bicyclic compounds are obtained by Lewis acid-catalyzed [2 + 2] cycloaddition reactions of 1-alkynyl triazenes and enones. In the presence of Me2AlCl, bicyclic [4.2.0] triazenes rearrange into [3.2.1] ring systems. The triazene function in the latter can be used for further functionalizations. Notably, we show that vinyl triazenes can serve as substrates for Pd-catalyzed cross-coupling reactions with arylboronic acids.

Competition between the Hiyama and Suzuki–Miyaura Pd-catalyzed cross-coupling reaction mechanisms for the formation of some regioselective derivatives of quinoxaline and benzofuran; Which reaction mechanism is more favorable?

Pd-NHC type complexes are supposed to have a high degree of participation in ‘C–C’ cross-coupling reactions, so they are commonly used in industry as well as academia. As regards the competition between Hiyama and Suzuki-Miyaura, this research aims to establish a more suitable reaction pathway and cross-coupling mechanism for the formation of certain derivatives of quinoxaline and benzofuran at the Cam-B3LYP-D3 theoretical level. First of all, the 2-phenyl-toluene formation cycle was determined using two specified cross-coupling reactions due to the presence of experimental 2-phenyl-toluene formation data in both Suzuki-Miyaura and Hiyama cross-coupling reactions. The mechanisms for the development of regioselective compounds 2-(2-methoxyphenyl)-6-p-tolylquinoxaline and 2,3-bis (4-chlorophenyle) benzofuran by Suzuki-Miyaura and Hiyama cross-coupling reactions are computationally compared to more suitable reaction pathways and cross-coupling reactions. In particular, our findings are consistent with the Pd-NHC type complex approach to this problem, which is more desirable for the development of regioselective compounds in competition between the various types of cross-coupling reaction mechanisms.

Substituent-Controlled Tailoring of Chalcogen-Bonded Supramolecular Nanoribbons in the Solid State.

In this work, we design and synthesize supramolecular 2,5-substituted chalcogenazolo[5,4-β]pyridine (CGP) synthons arranging in supramolecular ribbons at the solid state. A careful choice of the combination of substituents at the 2- and 5-positions on the CGP scaffold is outlined to accomplish supramolecular materials by means of multiple hybrid interactions, comprising both chalcogen and hydrogen bonds. Depending on the steric and electronic properties of the substituents, different solid-state arrangements have been achieved. Among the different moieties on the 5-position, an oxazole unit has been incorporated on the Se- and Te-congeners by Pd-catalyzed cross-coupling reaction and a supramolecular ribbon-like organization was consistently obtained at the solid state.

Highlights: Multilingual Safety Resources, Pd-Catalyzed Cross-Coupling Reactions, Ethylene Glycol Purification, and More

Highlights: Multilingual Safety Resources, Pd-Catalyzed Cross-Coupling Reactions, Ethylene Glycol Purification, and More

Pd-catalyzed oxidative Heck-type arylation of vinyl ketones, alkenes, and acrylates with Sb-aryl-tetrahydrodibenz[c,f][1,5]azastibocines

The Pd-catalyzed cross-coupling reactions of Sb-aryl-1,5-azastibocines with alkenes are described. The reactions of azastibocines with alkenes such as vinyl ketones, alkenes, and acrylates in the presence of 10 mol% PdCl2 at 80 °C in DMA under aerobic conditions produced Heck adducts in moderate-to-excellent yields. Single-crystal X-ray and NMR analysis revealed that the aryl donors in this reaction, the Sb-aryl-1,5-azastibocines, are hypervalent compounds that display N–Sb intramolecular non-bonding interaction. These are the first examples of Pd-catalyzed Heck-type arylations using heterocyclic hypervalent organoantimony compounds. Although the reactions proceeded efficiently with the azastibocines, they hardly progressed with trivalent and pentavalent triarylantimony reagents.

Stereoselectivity in Pd-catalysed cross-coupling reactions of enantioenriched nucleophiles.

Advances in Pd-catalysed cross-coupling reactions have facilitated the development of stereospecific variants enabling the use of configurationally stable, enantioenriched, main-group organometallic nucleophiles to form C(sp 3)-C(sp 2) bonds. Such stereospecific cross-coupling reactions constitute a powerful synthetic approach to attaining precise 3D control of molecular structure, allowing new stereogenic centres to be readily introduced into molecular architectures. Examples of stereospecific, Pd-catalysed cross-coupling reactions have been reported for isolable enantioenriched alkylboron, alkyltin, alkylgermanium and alkylsilicon nucleophiles. In these reactions, a single, dominant stereospecific pathway of transmetallation to palladium is required to effect efficient chirality transfer to the cross-coupled product. However, the potential for competing stereoretentive and stereoinvertive pathways of transmetallation complicates the stereochemical transfer in these processes and impedes the rational development of new stereospecific cross-coupling variants. In this Review, we describe the use of enantioenriched organometallic nucleophiles in stereospecific, Pd-catalysed cross-coupling reactions. We focus on systems involving well-defined, isolable, enantioenriched nucleophiles in which a clear stereochemical course of transmetallation is followed. Specific modes of electronic activation that influence the reactivity of alkylmetal nucleophiles are described and presented in the context of their impact on the stereochemical course of cross-coupling reactions. We expect that this Review will serve as a valuable resource to assist in deconvoluting the many considerations that potentially impact the stereochemical outcome of Pd-catalysed cross-coupling reactions.

Green synthesis of substituted olefins (Heck Cross-Coupling Reaction) with palladium(II) catalysts bearing heterodonor P/N ligands

To develop new hemilabile ligand systems for the green synthesis of substituted olefins via Heck cross-coupling reactions in supercritical CO2, we designed and synthesized three palladium(II) complexes bearing heterodonor phosphine-imine ligands which were effectively used in organic solvents in terms of various Pd-catalyzed cross-coupling reactions. These newly prepared palladium(II) complexes and previously reported analogs by us were modified with perfluorooctyl (-C8F17) groups to provide their solubilization in supercritical CO2 to be applied as homogenous catalyst. Both catalytic efficiency and selectivity were benchmarked in the Heck cross-coupling reactions, this representing the first example of the use of hemilabile phosphine-imines as ligands in supercritical CO2 solvent. This ligand system leads to lower reaction times, good conversions and selectivities than the previously reported well-known mono- or bisphosphine palladium precatalysts. Moreover, the phosphine-imine based palladium(II) precatalysts show tolerance of a wide variety of substrates on both olefin and aryl halides.

Diversely Functionalised Cytochalasins through Mutasynthesis and Semi-Synthesis.

Mutasynthesis of pyrichalasin H from Magnaporthe grisea NI980 yielded a series of unprecedented 4′‐substituted cytochalasin analogues in titres as high as the wild‐type system (≈60 mg L−1). Halogenated, O‐alkyl, O‐allyl and O‐propargyl examples were formed, as well as a 4′‐azido analogue. 4′‐O‐Propargyl and 4′‐azido analogues reacted smoothly in Huisgen cycloaddition reactions, whereas p‐Br and p‐I compounds reacted in Pd‐catalysed cross‐coupling reactions. A series of examples of biotin‐linked, dye‐linked and dimeric cytochalasins was rapidly created. In vitro and in vivo bioassays of these compounds showed that the 4′‐halogenated and azido derivatives retained their cytotoxicity and antifungal activities; but a unique 4′‐amino analogue was inactive. Attachment of larger substituents attenuated the bioactivities. In vivo actin‐binding studies with adherent mammalian cells showed that actin remains the likely intracellular target. Dye‐linked compounds revealed visualisation of intracellular actin structures even in the absence of phalloidin, thus constituting a potential new class of actin‐visualisation tools with filament‐barbed end‐binding specificity.

Synthesis of Symmetrical and Nonsymmetrical Polyenes by Iterative and Bidirectional Palladium-Catalyzed Cross-Coupling Reactions.

Bifunctional unsaturated reagents designed to undergo palladium-catalyzed cross-coupling reactions with complementary polyenyl connective fragments are highly useful for the undoubtedly challenging synthesis of polyenes. The current toolkit of building blocks for the bidirectional formation of Csp2 -Csp2 single bonds of polyenes includes homo-bisfunctionalized reagents with equal or unequal reactivity (due to steric and/or electronic factors), and hetero-bisfunctionalized counterparts containing either two different nucleophiles, two electrophiles or one of these functionalities and a latent nucleophile that can be unmasked when desired. The combination of these bifunctional linchpin reagents using tactics that modulate the reactivity of each terminus in order to achieve the required connection have streamlined the synthesis of polyenes of great complexity using (iterative) cross-coupling methods for Csp2 -Csp2 bond formation. Reaction conditions for the Pd-catalyzed cross-coupling reactions are mild and functional-group-tolerant, and therefore these protocols allow to construct the polyene structures using shorter unsaturated reactants with the desired geometries, since in general the products preserve the stereochemical information of the connected cross-coupling partners.

An efficient Pd-catalyzed intramolecular cyclization reaction followed by formation of benzimidazole derivatives: Synthesis of novel quinolin-fused benzo[d] azeto[1,2-a]benzimidazole analogues

Novel quinolin-fused benzo[d]azeto[1,2-a]benzimidazole analogues have been synthesized from o-phenylene diamine and various substituted 2-chloro-5-(2-methylquinoline-4-yl) benzaldehyde through Pd-mediated simultaneous CH–NH and CH–CX bond activation via intramolecular cyclization reaction followed by formation of benzimidazole derivatives. Developed two step, one pot route for quinoline fused four membered azeto[1,2-a] benzimidazole derivatives through Pd-catalyzed cross coupling reaction. The synthesis was carried out by using Pd2(dba)3 as a catalyst, Xphos as a ligand, Cs2CO3 as a base and toluene as a solvent and developed its mechanistic pathway.

Pd-Catalyzed Functionalization of Aryl Amines on a Soluble Polymer Support

AbstractHerein we report the use of a soluble polymer support PEG-2000 on Pd-catalyzed reactions to improve the functionalization of aromatic amines and the synthesis of N-heterocycles. Compatibility of metal-catalyzed reactions for assembling privileged structures such as functionalized anilines were studied. PEG-supported anilines were found to be suitable substrates for Pd-catalyzed N-arylation, Sonogashira and Heck reactions. PEGylated substrates were prepared in yields up to 94%. This work consists on a proof of concept on the use of PEGylated anilines on Pd-catalyzed cross-coupling reactions. Indole core was attained in 82% and 62% yields, via two different routes.

Selective Arylation of 2-Bromo-4-chlorophenyl-2-bromobutanoate via a Pd-Catalyzed Suzuki Cross-Coupling Reaction and Its Electronic and Non-Linear Optical (NLO) Properties via DFT Studies.

In the present study, 2-bromo-4-chlorophenyl-2-bromobutanoate (3) was synthesized via the reaction of 2-bromo-4-chlorophenol with 2-bromobutanoyl bromide in the presence of pyridine. A variety of 2-bromo-4-chlorophenyl-2-bromobutanoate derivatives (5a–f) were synthesized with moderate to good yields via a Pd-catalyzed Suzuki cross-coupling reaction. To find out the reactivity and electronic properties of the compounds, Frontier molecular orbital analysis, non-linear optical properties, and molecular electrostatic potential studies were performed.

Synthesis of glucoside-based imidazolium salts for Pd-catalyzed cross-coupling reaction in water

Sugar-based imidazolium salts (IMSs) represent an outstanding type of material making them eye-catching for a wide variety of applications. Herein, a series of glucoside-based IMSs (Glu-IMSs) combining glucoside and imidazolium head groups with different substituents were synthesized. The catalytic activities of these Glu-IMSs were evaluated by Pd-catalyzed Heck–Mizoroki and Suzuki–Miyaura reactions in water. Among them, the Glu-IMSs contain both –OH and NHCs coordination sites was found to be the most efficient ancillary ligand in comparison with other Glu-IMSs with just single NHCs coordination site. The HR-TEM analysis showed that the palladium nanoparticles stabilized by the Glu-IMSs with an average size of ~4.0 nm was formed in the reaction system, which may be act as an efficient real catalytic species. Under the optimized reaction conditions, a series of novel fluorine-cored organic small molecule functional materials were synthesized with favorable yields.

Pd(NHC)(μ-Cl)Cl]2: Versatile and Highly Reactive Complexes for Cross-Coupling Reactions that Avoid Formation of Inactive Pd(I) Off-Cycle Products.

SummaryThe development of more reactive, general, easily accessible, and readily available Pd(II)–NHC precatalysts remains a key challenge in homogeneous catalysis. In this study, we establish air-stable NHC–Pd(II) chloro-dimers, [Pd(NHC)(μ-Cl)Cl]2, as the most reactive Pd(II)–NHC catalysts developed to date. Most crucially, compared with [Pd(NHC)(allyl)Cl] complexes, replacement of the allyl throw-away ligand with chloride allows for a more facile activation step, while effectively preventing the formation of off-cycle [Pd2(μ-allyl)(μ-Cl)(NHC)2] products. The utility is demonstrated via broad compatibility with amide cross-coupling, Suzuki cross-coupling, and the direct, late-stage functionalization of pharmaceuticals. Computational studies provide key insight into the NHC–Pd(II) chloro-dimer activation pathway. A facile synthesis of NHC–Pd(II) chloro-dimers in one-pot from NHC salts is reported. Considering the tremendous utility of Pd-catalyzed cross-coupling reactions and the overwhelming success of [Pd(NHC)(allyl)Cl] precatalysts, we believe that NHC–Pd(II) chloro-dimers, [Pd(NHC)(μ-Cl)Cl]2, should be considered as go-to precatalysts of choice in cross-coupling processes.