Pd Catalysis Research Articles

Enantioselective Three‐Component α‐Allylic Alkylation of α‐Amino Esters by Synergistic Photoinduced Pd/Carbonyl Catalysis

Photoinduced excited‐state Pd catalysis has emerged as an intriguing strategy for unlocking new reactivity potential of simple substrates. However, the related transformations are still limited and the enantiocontrol remains challenging. Organocatalysis displays unique capability in substrate activation and stereocontrol. Combination of organocatalysis and photoinduced excited‐state Pd catalysis may provide opportunities to develop new enantioselective reactions from simple substrates. By applying cooperative triple catalysis including excited‐state Pd catalysis, ground‐state Pd catalysis, and carbonyl catalysis, we have successfully realized enantioselective α‐allylic alkylation of α‐amino esters with simple styrene and alkyl halide starting materials. The reaction allows rapid modular assembly of the three reaction partners into a variety of chiral quaternary α‐amino esters in good yields with 90‐99% ee, without protecting group manipulations at the active NH2 group. The cooperation of the chiral pyridoxal catalyst and the chiral phosphine ligand accounts for the excellent chirality induction.

Enantioselective Three‐Component α‐Allylic Alkylation of α‐Amino Esters by Synergistic Photoinduced Pd/Carbonyl Catalysis

Photoinduced excited‐state Pd catalysis has emerged as an intriguing strategy for unlocking new reactivity potential of simple substrates. However, the related transformations are still limited and the enantiocontrol remains challenging. Organocatalysis displays unique capability in substrate activation and stereocontrol. Combination of organocatalysis and photoinduced excited‐state Pd catalysis may provide opportunities to develop new enantioselective reactions from simple substrates. By applying cooperative triple catalysis including excited‐state Pd catalysis, ground‐state Pd catalysis, and carbonyl catalysis, we have successfully realized enantioselective α‐allylic alkylation of α‐amino esters with simple styrene and alkyl halide starting materials. The reaction allows rapid modular assembly of the three reaction partners into a variety of chiral quaternary α‐amino esters in good yields with 90‐99% ee, without protecting group manipulations at the active NH2 group. The cooperation of the chiral pyridoxal catalyst and the chiral phosphine ligand accounts for the excellent chirality induction.

The Cross-selectivity in Pd-catalyzed coupling of simple aryl C-H bonds

Abstract Pd-catalyzed cross-couplings of C-H bonds have been pursued by researchers to produce unsymmetrical C-C bonds directly for over fifty years, which are currently prepared by Suzuki, Kumada, Stille, Neigishi, Heck, or Sonogashira coupling of C-halogen with C-M or C-H bonds. A big challenge is to obtain the high cross-selectivity of cross-coupling products, especially when the substrates have similar chemical C-H bonds, such as simple arenes. Lu and co-workers have studied Pd catalysis in the cross-couplings of aryl C-H bonds since 2003. This account introduces their strategy, understanding and research in cross-selectivity control, C-H activation mode, cross-coupling establishment and application in synthesis. 1 Introduction 2 Cross-selectivity Control 3 Conclusion

Multisite modifications of arenes using ketones as removable handles enabled by Pd and norbornene cooperative catalysis

Multisite modifications of arenes using ketones as removable handles enabled by Pd and norbornene cooperative catalysis

Insights into the Synergistic Interplay of Ligand and Base Effects in Palladium-Catalyzed Enantioselectivity Hydrofunctionalization of Dienes.

Transition-metal-catalyzed enantioselective C-O bond constructions via hydrofunctionalization involving the use of O-based nucleophiles are an important topic in synthetic chemistry. Herein, density functional theory calculations were conducted to unveil the mechanism and enantioselectivity of Pd-catalyzed asymmetric hydrofunctionalization of conjugated dienes. We found that the base-assisted 4,3-activation model of the ligand-to-ligand hydrogen transfer (LLHT) mechanism is the most preferred one among all the cases, which could be ascribed to the favorable C-H···O interactions and the electrostatic interactions. For the enantioselective C-O bond formation process, the orientation of the substrate in the chiral pocket plays a significant role in controlling the enantioselectivity by contributing different noncovalent interactions. On the basis of the distortion/interaction model and energy decomposition analysis, the distortion energy is identified as the dominant factor controlling the product chemoselectivity. BnOH acts as the substrate, proton shuttle, and stabilizer to facilitate the H-transfer process in both LLHT and the C-O bond formation process. This study provides molecular-level insights into the collaborative effect of the base and P,N-ligand to perform the catalytic activity in the asymmetric hydrofunctionalization of conjugated dienes, which might open a new avenue for designing more efficient base-assisted enantioselective hydrofunctionalization by Pd catalysis.

Deuteration and Tritiation of Pharmaceuticals by Non-Directed Palladium-Catalyzed C-H Activation in Heavy and Super-Heavy Water.

Deuterated and tritiated analogs of drugs are valuable compounds for pharmaceutical and medicinal chemistry. In this work, we present a novel hydrogen isotope exchange reaction of drugs using non-directed homogeneous Pd-catalysis. Aromatic C-H activation is achieved by a commercially available pyridine ligand. Using the most convenient and cheapest deuterium source, D2O, as the only solvent 39 pharmaceuticals were labelled with clean reaction profiles and high deuterium uptakes. Additionally, we describe the first application of non-directed homogeneous Pd-catalysis for H/T exchange on three different pharmaceuticals by using T2O as isotopic source, demonstrating the applicability to the synthesis of radiotracers.

CsPbX3 Nanocrystal Incorporating Transition Metal Cocatalyst for Photocatalytic Organic Transformation by Single Electron Transfer

ABSTRACTThe construction of composite photocatalysts is a promising strategy for improving the overall catalytic efficiency in organic photochemical transformation. In this study, we synthesize a series of inorganic metal perovskite CsPbX3 (X = Cl, Br, I) nanocrystals (NCs) with excellent chemical stability and wide‐range visible‐light absorption. The Pd cocatalyst is then induced to the surfaces of CsPbX3 fabricating Pd/CsPbX3 composites via visible‐light reduction method. Photoelectrochemical measurements show the introduction of Pd cocatalyst promotes efficiently the charge separation and transfer of CsPbX3. The prepared Pd/CsPbX3 composites exhibit remarkable photocatalytic efficiency in visible‐light‐induced C–C cross‐coupling reaction. The reaction is characterized by mild reaction conditions, good recyclability, and high yield from a broad variety of substrates. Mechanism investigations show the reaction relies on the synergy of CsPbX3 photocatalysis and Pd catalysis. The valence band of CsPbX3 oxidizes the phenylboronic acid into active radical species via single electron transfer. On another hand, Pd(0) as active sites occurs oxidative addition with aryl halides for achieving the C–C cross‐coupling reaction. This study displays a feasible approach for the introduction of Pd catalyst in CsPbX3 to achieve the photocatalytic organic transformation via photoinduced electron transfer.

Aziridines as Versatile C(sp3) Precursors in Transition-Metal Catalyzed Cross-Coupling Strategies

Aziridines, which serve as valuable scaffolds in numerous pharmaceuticals and bioactive molecules, have emerged as highly efficient C(sp3) precursors in the realm of organic chemistry. Particularly, employing aziridines as versatile electrophiles in transition metal-catalyzed cross-coupling has enabled precise control over the regiochemistry in the formation of new C(sp3)-C, Si, B bonds. This review explores recent innovative aziridine cross-coupling approaches using Ni or Pd catalysis, highlighting initial findings of new mechanistic approaches and delineating distinct catalytic pathways.

Enantioselective 1,2-Carboamination of 1,3-Dienes with N-Hydroxyphthalimide (NHP) Esters Enabled by a Photoinduced Pd Catalysis.

Herein, a photoinduced, Pd-catalyzed direct 1,2-carboamination of conjugated 1,3-dienes has been successfully achieved. Sequential regioselective C-C bond and enantioselective C-N bond formation allows rapid assembly of a wide range of value-added chiral allylic amines from readily available N-hydroxyphthalimide (NHP) esters and 1,3-dienes under mild conditions. This developed protocol further demonstrates the versatility and potency of the photoexcited Pd catalytic system with a bifunctional reagent in the streamlined difunctionalization of C═C bonds.

Alcohols as Alkyl Electrophiles for Deoxygenative Heck Reaction Enabled by Excited State Pd Catalysis.

Here, we present a general method for the photoinduced Pd-catalyzed deoxygenative Heck reaction of vinyl arenes with ortho-iodophenyl-thionocarbonate derived from alcohols. Mechanistic studies reveal that the deoxygenation involves a 5-endo-trig cyclization and fragmentation process, with radical addition identified as the rate-determining step in this transformation. This one-pot procedure demonstrates excellent selectivity for less hindered hydroxyl groups in diols, facilitating late-stage functionalization of complex molecules and scalability to gram-scale synthesis. The protocol highlights significant synthetic potential and can be extended to the cascade 1,1-difunctionalization of isocyanides and the intermolecular radical cascade cyclization of N-arylacrylamides.

Pd-Catalyzed Borylation in Water and Its Application to the Synthesis of Active Pharmaceutical Ingredient (API) Intermediates.

An efficient catalytic borylation reaction of aryl bromides in water based on Pd catalysis under micellar conditions is presented. The peculiar combination of the proper Pd precursor with a Sphos ligand and a hindered lipophilic base ensures good yields in the synthesis of a wide range of boronic esters, even for heteroaryl derivatives with a good purity profile. The method is specifically developed for the in situ preparation of boronic esters that are directly converted into examples of relevant active pharmaceutical ingredient intermediates through cross-coupling reactions or via oxidation to phenols.

Synthesis of Angular Polycyclic Aromatic Molecules Via Pd‐Catalyzed Decarboxylative Cycloaddition of 2‐Alkylidenetrimethylene Carbonates with Quinazoline‐Derived Azomethine Imines

AbstractA formal [4+3] cycloaddition of 2‐alkylidenetrimethylene carbonates with quinazoline‐derived azomethine imines is described. Under Pd catalysis, the reaction works efficiently under room temperature to afford angular quinazoline‐fused seven‐membered N,N,O‐heterocycles. A variety of cyclic carbonates and azomethine imines were well tolerated under mild reaction conditions. This work demonstrates the synthetic utility of decarboxylative cycloadditions of 2‐alkylidenetrimethylene carbonates for the synthesis of angular polycyclic aromatic molecules.

Enantioselective Arylation of Sulfenamides to Access Sulfilimines Enabled by Palladium Catalysis.

Sulfur-containing functional groups have garnered considerable attention due to their common occurrence in ligands, pharmaceuticals, and insecticides. Nevertheless, enantioselective synthesis of sulfilimines, particularly diaryl sulfilimines remains a challenging and persistent goal. Herein we report a highly enantio- and chemoselective cross-coupling of sulfenamides with aryl diazonium salt to construct diverse S(IV) stereocenters by Pd catalysis. Bisphosphine ligands bearing sulfinamide groups play a crucial role in achieving high reactivity and selectivity. This approach provides a general, modular and divergent framework for quickly synthesizing chiral sulfilimines and sulfoximines that are otherwise challenging to access. In addition, the origins of the high chemoselectivity and enantioselectivity were extensively investigated using density functional theory calculations.

Enantioselective Arylation of Sulfenamides to Access Sulfilimines Enabled by Palladium Catalysis

AbstractSulfur‐containing functional groups have garnered considerable attention due to their common occurrence in ligands, pharmaceuticals, and insecticides. Nevertheless, enantioselective synthesis of sulfilimines, particularly diaryl sulfilimines remains a challenging and persistent goal. Herein we report a highly enantio‐ and chemoselective cross–coupling of sulfenamides with aryl diazonium salt to construct diverse S(IV) stereocenters by Pd catalysis. Bisphosphine ligands bearing sulfinamide groups play a crucial role in achieving high reactivity and selectivity. This approach provides a general, modular and divergent framework for quickly synthesizing chiral sulfilimines and sulfoximines that are otherwise challenging to access. In addition, the origins of the high chemoselectivity and enantioselectivity were extensively investigated using density functional theory calculations.

Visible light excitation on CuPd/TiN with enhanced chemisorption for catalyzing heck reaction

In this work, we developed plasmonic photocatalyst composed of CuPd alloy nanoparticles supported on TiN, the optimized Cu3Pd2/TiN catalyst shows excellent conversion (>96 %) and selectivity (>99 %) for Heck reaction at 50 °C under visible light irradiation. By in-situ spectroscopic investigations, we find that visible light excitation could achieve stable metallic Cu species on the surface of CuPd alloy nanoparticles, thereby eliminating the inevitable surface oxides of Cu based catalyst. The in-situ formed metallic Cu species under irradiation take advantage of the strong interactions of Cu with visible light, and manifest in the localized surface plasmon resonances (LSPR) photoexcitation. Visible light excitation could further promote the charge transfer between catalytic Pd component and the support TiN, resulting in electron-rich Pd sites on CuPd/TiN. Moreover, light excitation on CuPd/TiN generates strong chemisorption of iodobenzene and styrene, favoring the activation of reactants for Heck reaction. DFT calculations suggest that electron-rich CuPd sites ideally lower the activation energy barrier for the coupling reaction. This work provides valuable insights for mechanistic understanding of plasmonic photocatalysis.

Metal immobilized in a USY zeolite-supported (4-CB)TPPB: A new strategy of enhanced stability for acetylene hydrochlorination

Palladium (Pd)-based catalysts supported by silicaluminate materials are potential as the efficient non-mercury catalyst for acetylene hydrochlorination, which is a necessary industrial reaction for producing vinyl chloride monomer. A new strategy was employed to improve Pd/USY zeolite catalysts taking advantage of 4-carboxybutyl triphenylphosphonium bromide ((4-CB)TPPB) for acetylene hydrochlorination. The most active catalyst (Pd@20(4-CB)TPPB/USY) with the 0.5 wt% Pd loadings and the 20 wt% (4-CB)TPPB additives could achieve a stable acetylene conversion of 99.9 % and the vinyl chloride selectivity of 99.7 % during more than 50 h, outperforming the Pd/USY catalyst. The additive of (4-CB)TPPB was preferential to stabilize the catalytic active Pd species, inhibit the Pd (II) reduction and change the surface acidic properties during the preparation process and reaction, hence restraining the carbon deposition. Density functional theory (DFT) calculations further indicate that (4-CB)TPPB additives could effectively enhance the adsorption energy of catalyst for reactants and the desorption energy of vinyl chloride monomer (VCM) products, thus inhibiting the carbon deposition for improving the catalytic performance of Pd/USY catalysts. These findings provide guidance for designing efficient Pd-based catalysts as well as their utilization for acetylene hydrochlorination.

Co-Removal of Perfluorooctanoic Acid and Nitrate from Water by Coupling Pd Catalysis with Enzymatic Biotransformation.

PFAS (poly- and per-fluorinated alkyl substances) represent a large family of recalcitrant organic compounds that are widely used and pose serious threats to human and ecosystem health. Here, palladium (Pd0)-catalyzed defluorination and microbiological mineralization were combined in a denitrifying H2-based membrane biofilm reactor to remove co-occurring perfluorooctanoic acid (PFOA) and nitrate. The combined process, i.e., Pd-biofilm, enabled continuous removal of ∼4 mmol/L nitrate and ∼1 mg/L PFOA, with 81% defluorination of PFOA. Metagenome analysis identified bacteria likely responsible for biodegradation of partially defluorinated PFOA: Dechloromonas sp. CZR5, Kaistella koreensis, Ochrobacterum anthropic, and Azospira sp. I13. High-performance liquid chromatography-quadrupole time-of-flight mass spectrometry and metagenome analyses revealed that the presence of nitrate promoted microbiological oxidation of partially defluorinated PFOA. Taken together, the results point to PFOA-oxidation pathways that began with PFOA adsorption to Pd0, which enabled catalytic generation of partially or fully defluorinated fatty acids and stepwise oxidation and defluorination by the bacteria. This study documents how combining catalysis and microbiological transformation enables the simultaneous removal of PFOA and nitrate.

Tandem One-Pot Synthesis of 2H- and 3H-Pyrroles Enabled by Dual Rh(II)/Pd(0) Catalysis

AbstractRegioselective approaches toward 2H- and 3H-pyrroles, which are biologically important but easily isomerizable compounds, have been successfully achieved via dual Rh(II)/Pd(0) relay catalysis and DBU-mediated processes in one-pot operation using N-tosyltriazoles and hydroxymethylallyl carbonates. In this transformation, readily accessible N-tosyltriazoles were enabled as stable nitrogen sources for the two scaffolds, and the regioselectivity was controlled by the substituent positions of the hydroxymethylallyl carbonates.

Extracellular Vesicles-Mediated Bio-Orthogonal Catalysis in Growing Tumors.

Several studies have reported the successful use of bio-orthogonal catalyst nanoparticles (NPs) for cancer therapy. However, the delivery of the catalysts to the target tissues in vivo remains an unsolved challenge. The combination of catalytic NPs with extracellular vesicles (EVs) has been proposed as a promising approach to improve the delivery of therapeutic nanomaterials to the desired organs. In this study, we have developed a nanoscale bio-hybrid vector using a CO-mediated reduction at low temperature to generate ultrathin catalytic Pd nanosheets (PdNSs) as catalysts directly inside cancer-derived EVs. We have also compared their biodistribution with that of PEGylated PdNSs delivered by the EPR effect. Our results indicate that the accumulation of PdNSs in the tumour tissue was significantly higher when they were administered within the EVs compared to the PEGylated PdNSs. Conversely, the amount of Pd found in non-target organs (i.e., liver) was lowered. Once the Pd-based catalytic EVs were accumulated in the tumours, they enabled the activation of a paclitaxel prodrug demonstrating their ability to carry out bio-orthogonal uncaging chemistries in vivo for cancer therapy.

Efficient catalysis of Pd (II) supported by thiourea covalent organic framework in Suzuki coupling reaction

Covalent organic frameworks (COFs) were ideal carriers for noble metal catalysts due to their rich pore structure, pre-designable monomers, and high stability. Herein, a series of novel thiourea-based COFs (Tx-COFs) enriched with heteroatoms were constructed to provide abundant and powerful anchoring sites for metal. The successful preparation of Pd@COFs with high metal dispersion and substantial active sites was confirmed by XPS and STEM-EDX element mapping. These catalysts exhibited excellent catalytic activity and stability for the Suzuki-Miyaura coupling reaction. Especially for Pd@TU-COF, the catalyst still catalyzed the reaction at room temperature to afford the product in a yield of 99 % after 10 reuses, while the palladium load only decreased from 5.78 % to 5.66 %. The structure-activity relationships between the metal loading mode, the structure of Tx-COF, and its catalytic performance were also investigated in this study, which provided a feasible strategy for the preparation of efficient and stable heterogeneous catalysts.