Carbonylative Suzuki Miyaura Coupling Research Articles

Triazine-wingtips accelerated NHC-Pd catalysed carbonylative Suzuki cross-coupling reaction

Triazine conjugated N-heterocyclic carbene palladium complexes were synthesized for reducing the Pd amount in the catalysts to the ppm levels. This work reports the carbonylative Suzuki-Miyaura coupling of aryl iodides catalyzed by N-heterocyclic carbenes palladium with triazine wingtips (T-NHC-Pd). More importantly, the palladacycles have been used to generate high turnover numbers (TON's) and turnover frequencies (TOF's).

Carbonylative Transformations Using a DMAP-Based Pd-Catalyst through Ex Situ CO Generation.

A phosphine-free, efficient protocol for aminocarbonylation and carbonylative Suzuki-Miyaura coupling has been developed using a novel palladium complex, [PdII(DMAP)2(OAc)2]. The complex was successfully synthesized using a stoichiometric reaction between PdII(OAc)2 and DMAP in acetone at room temperature and characterized using single-crystal X-ray analysis. Only 5 mol % catalyst loading was sufficient for effective carbonylative transformations. "Chloroform-COware" chemistry was utilized for safe and facile insertion of the carbonyl unit using chloroform as an inexpensive CO source in a two-chamber setup. Various value-added pharmaceutically relevant compounds such as CX-516, CX-546, and farampator were synthesized using the technique. Furthermore, the commercially designed COware was engineered to COware-RB setup for sequential one-pot synthesis of indenoisoquinolines (topoisomerase I inhibitors).

Mechanistic insights and computational design of Cu/M bimetallic synergistic catalysts for Suzuki-Miyaura coupling of arylboronic esters with alkyl halides

Carbonylative Suzuki-Miyura coupling reaction is one of the most efficient methods to synthetize ketones. In this work, the reaction mechanism of arylboronic esters with alkyl halides catalyzed by Cu/Mn synergistic catalysts has been studied by DFT calculation. The calculated results show that the whole reaction contains two cycles, one is the Cu-catalyzed transformation of Ar-Bneop to RO-Bneop, and the other is Mn-catalyzed Heck–Breslow cycle for alkyl halide carbonylation. At the last step, the final product aryl ketone is produced through the C-C cross-coupling between the two intermediates, which form from the above separate two cycles. For the title reaction, the [Mn(CO)5]− catalyzed the Heck–Breslow cycle belongs to SN2 mechanism, and Mn2(CO)10 catalyzed cycle is SET mechanism. In addition to [Mn(CO)5]−, the metal carbonyl anions with moderate even low nucleophilicity are suitable to co-catalyze the carbonylative Suzuki-Miyaura coupling with the Cu-carbene catalyst. Our calculation results are consistent with and provide explanations the experimental observations, as well as shed lights on further advancement of new bimetallic catalysts.

A Metal-Organic Framework (MOF)-Based Multifunctional Cargo Vehicle for Reactive-Gas Delivery and Catalysis.

The efficient delivery of reactive and toxic gaseous reagents to organic reactions was studied using metal-organic frameworks (MOFs). The simultaneous cargo vehicle and catalytic capabilities of several MOFs were probed for the first time using the examples of aromatization, aminocarbonylation, and carbonylative Suzuki-Miyaura coupling reactions. These reactions highlight that MOFs can serve a dual role as a gas cargo vehicle and a catalyst, leading to product formation with yields similar to reactions employing pure gases. Furthermore, the MOFs can be recycled without sacrificing product yield, while simultaneously maintaining crystallinity. The reported findings were supported crystallographically and spectroscopically (e.g., diffuse reflectance infrared Fourier transform spectroscopy), foreshadowing a pathway for the development of multifunctional MOF-based reagent-catalyst cargo vessels for reactive gas reagents as an attractive alternative to the use of toxic pure gases or gas generators.

A Metal‐Organic Framework (MOF)‐Based Multifunctional Cargo Vehicle for Reactive‐Gas Delivery and Catalysis

AbstractThe efficient delivery of reactive and toxic gaseous reagents to organic reactions was studied using metal‐organic frameworks (MOFs). The simultaneous cargo vehicle and catalytic capabilities of several MOFs were probed for the first time using the examples of aromatization, aminocarbonylation, and carbonylative Suzuki–Miyaura coupling reactions. These reactions highlight that MOFs can serve a dual role as a gas cargo vehicle and a catalyst, leading to product formation with yields similar to reactions employing pure gases. Furthermore, the MOFs can be recycled without sacrificing product yield, while simultaneously maintaining crystallinity. The reported findings were supported crystallographically and spectroscopically (e.g., diffuse reflectance infrared Fourier transform spectroscopy), foreshadowing a pathway for the development of multifunctional MOF‐based reagent‐catalyst cargo vessels for reactive gas reagents as an attractive alternative to the use of toxic pure gases or gas generators.

Copper-Catalyzed Carbonylative Coupling of Alkyl Halides.

Transition metal-catalyzed carbonylation reactions represent a direct and atom-economical approach to introduce oxygen functionality into organic compounds, with CO acting as an inexpensive and readily available C1 feedstock. Despite the long history of carbonylation catalysis, including many processes that have been industrialized at bulk scale, there remain several challenges to tackle. For example, noble metals such as Pd, Rh, and Ir are typically used as catalysts for carbonylation reactions, rather than earth-abundant alternatives. Additionally, while carbonylation of C(sp2)-hybridized substrates (e.g., aryl halides) is well-known, carbonylation of unactivated alkyl electrophiles, especially where β-hydride elimination can compete with desired CO migratory insertion at the catalyst site, remains challenging for many systems. Recently, base metal catalysis based on Mn, Co, and other metals has enabled advances in carbonylative coupling of alkyl electrophiles, though the nucleophiles are often limited to alcohols or amines to generate esters or amides as products. Thus, we have targeted base metal-catalyzed carbonylative C-C and C-E (E = N, H, Si, B) coupling reactions as a method for approaching diverse carbonyl compounds of synthetic importance.Initially, we designed a heterobimetallic catalyst platform for carbonylative C-C coupling of alkyl halides with arylboronic esters (i.e., carbonylative Suzuki-Miyaura coupling) to generate aryl alkyl ketones. Subsequently, we developed multicomponent carbonylation reactions of alkyl halides using NHC-Cu catalysts (NHC = N-heterocyclic carbene). These reactions operate by radical mechanisms, converting alkyl halides into either acyl radical or acyl halide intermediates that undergo subsequent C-C or C-E coupling at the Cu site. This mechanistic paradigm is relatively novel in the metal-catalyzed carbonylation area, allowing us to discover a previously unexplored chemical space in carbonylative coupling catalysis. We have successfully developed the following reactions: (a) hydrocarbonylative coupling of alkynes with alkyl halides; (b) borocarbonylative coupling of alkynes with alkyl halides; (c) reductive aminocarbonylation of alkyl halides with nitroarenes; (d) reductive carbonylation of alkyl halides; (e) carbonylative silylation of alkyl halides; (f) carbonylative borylation of alkyl halides. These reactions provide a broad range of valuable products including ketones, allylic alcohols, β-borylenones, amides, alcohols, acylsilanes, and acylborons in an efficient manner. Notably, the preparation of some of these products has previously required multistep syntheses, harsh conditions, or specialized reagents. By contrast, the multicomponent coupling platform that we have developed requires only readily available building blocks and rapidly increases molecular complexity in a single synthetic manipulation.

Carboxyboronate as a Versatile In Situ CO Surrogate in Palladium‐Catalyzed Carbonylative Transformations

AbstractThe application of carboxy‐MIDA‐boronate (MIDA=N‐methyliminodiacetic acid) as an in situ CO surrogate for various palladium‐catalyzed transformations is described. Carboxy‐MIDA‐boronate was previously shown to be a bench‐stable boron‐containing building block for the synthesis of borylated heterocycles. The present study demonstrates that, in addition to its utility as a precursor to heterocycle synthesis, carboxy‐MIDA‐boronate is an excellent in situ CO surrogate that is tolerant of reactive functionalities such as amines, alcohols, and carbon‐based nucleophiles. Its wide functional‐group compatibility is highlighted in the palladium‐catalyzed aminocarbonylation, alkoxycarbonylation, carbonylative Sonogashira coupling, and carbonylative Suzuki–Miyaura coupling of aryl halides. A variety of amides, esters, (hetero)aromatic ynones, and bis(hetero)aryl ketones were synthesized in good‐to‐excellent yields in a one‐pot fashion.

Carbon Nanotube Supported Ni/Pd-Nanoparticles on for Carbonylative Suzuki–Miyaura Coupling

Carbon Nanotube Supported Ni/Pd-Nanoparticles on for Carbonylative Suzuki–Miyaura Coupling

Carbonylative Suzuki–Miyaura Coupling Reactions of Aryl Iodides with Readily Available Polymer-Immobilized Palladium Nanoparticles

Polysilane/alumina-supported palladium nanoparticle catalyzed carbonylative Suzuki–Miyaura coupling reactions under ligand-free conditions have been developed to synthesize diaryl ketones. High yields and selectivities were achieved even with low catalyst loading under atmospheric pressure of CO gas. A variety of aryl iodides and arylboronic acids could be utilized to afford the diaryl ketones in excellent yields. Moreover, the ligand-free immobilized palladium nanoparticles could be recovered by simple filtration and the catalytic activity could be maintained for several runs.

Novel and efficient bridged bis(N‐heterocyclic carbene)palladium(II) catalysts for selective carbonylative Suzuki–Miyaura coupling reactions to biaryl ketones and biaryl diketones

Bridged N,N′‐substituted bisbenzimidazolium bromide salts (L1, L2, and L3) were synthesized and fully characterized. Reactions of palladium acetate with L1, L2, and L3 afforded corresponding new bridged bis(N‐heterocyclic carbene)palladium(II) complexes (C1, C2, and C3) in high yields. The X‐ray structure of complex C1 showed that the Pd(II) ion is bonded to the two carbon atoms of the bis(N‐heterocyclic carbene) and two bromido ligands are in the cis position, resulting in a distorted square planar geometry. The three Pd(NHC)2Br2 complexes C1, C2, and C3 were evaluated in carbonylative Suzuki–Miyaura coupling reactions of aryl boronic acids with aryl halides and displayed high catalytic activity with low catalyst loading. The coupling reactions of aryl bromides were selective towards the carbonylation product at higher carbon monoxide pressure.

Xantphos‐ligated palladium dithiolates: An unprecedented and convenient catalyst for the carbonylative Suzuki–Miyaura cross‐coupling reaction with high turnover number and turnover frequency

Xantphos‐ and dithiolate‐ligated macrocyclic palladium complexes as an efficient and stable catalyst for the carbonylative Suzuki–Miyaura cross‐coupling reaction have been synthesized. The catalysts were characterized by 1H‐nuclear magnetic resonance (NMR), CHNS (carbon, hydrogen, nitrogen, and sulfur) analysis, melting point analysis, and 31P‐NMR spectroscopy. Several sensitive functional groups (e.g., –NO2, –F, –Cl, –Br, –NH2, and –CN) on the aromatic ring were well tolerated in the carbonylative Suzuki–Miyaura coupling reaction. The present palladium complexes produce six times higher turnover number (TON) and five times higher turnover frequency (TOF) compared with conventional homogeneous palladium precursors. Maximum TONs in the range of 105 to 106 and TOF in the range of 104 to 105 could be generated by a very low amount of catalyst loading (10–5 mol%).

“CO” as a Carbon Bridge to Build Complex C2-Branched Glycosides Using a Palladium-Catalyzed Carbonylative Suzuki–Miyaura Reaction from 2-Iodoglycals

Development of a palladium-catalyzed carbonylative Suzuki-Miyaura coupling reaction between 2-iodoglycal partners and diverse aryl- and alkenyl-boronic acids is presented, leading to original 2-ketoglycals. The newly formed carbonyl link could be exploited to access 2-aryl/alkenyl-methylene-α-glucopyranoside scaffolds via a three-step sequence including an indium-mediated Ferrier-type reaction.

Amine-Functionalized Graphene Oxide-Stabilized Pd Nanoparticles (Pd@APGO): A Novel and Efficient Catalyst for the Suzuki and Carbonylative Suzuki–Miyaura Coupling Reactions

Palladium nanoparticles (NPs) are decorated on the surface of an amine-functionalized graphene oxide (Pd@APGO) and characterized by using various analytical techniques. In this methodology, the surface of graphene oxide is modified using the amine functional groups which help stabilization and distribution of Pd NPs very well and increases the surface electron density of NPs by electron donating from amine groups. This developed catalyst shows a high catalytic activity toward the Suzuki coupling and carbonylative Suzuki–Miyaura coupling reactions at mild reaction conditions. The amine on the graphene oxide plays a very crucial role to stabilize and increase the electron density of Pd NPs and prevents the leaching of Pd metals. The Pd@APGO catalyst showed excellent catalytic activity (>90%) with a large range of substrates for both of the reactions and provides five recycle runs without the loss of its activity.

Efficient N-heterocyclic carbene palladium(II) catalysts for carbonylative Suzuki-Miyaura coupling reactions leading to aryl ketones and diketones

New N, N′-substituted imidazolium salts (L1 and L2) and their corresponding diiodopyridinepalladium(II) complexes (C1 and C2) were successfully synthesized and characterized. Reactions of palladium iodide with the newly synthesized N, N′-substituted imidazolium iodides in pyridine afforded the corresponding new palladium-N-heterocyclic carbene pyridine complexes in high yields. The new palladium(II) complex C1 was characterized by single crystal X-ray diffraction analysis. The Pd(II) ion is bonded to the nitrogen atom of the pyridine, the carbon atom of the NHC carbene ligand and two trans iodides resulting in distorted square planar geometry. The two Pd-NHC-Py complexes C1 and C2 displayed higher catalytic activity in the carbonylative Suzuki-Miyaura coupling reactions with much lower catalyst loading as compared to the catalytic systems reported in the literature.

Cu/Mn bimetallic catalysis enables carbonylative Suzuki-Miyaura coupling with unactivated alkyl electrophiles.

A bimetallic system consisting of Cu-carbene and Mn-carbonyl co-catalysts was employed for carbonylative C-C coupling of arylboronic esters with alkyl halides, allowing for the convergent synthesis of ketones. The system operates under mild conditions and exhibits complementary reactivity to Pd catalysis. The method is compatible with a wide range of arylboronic ester nucleophiles and proceeds smoothly for both primary and secondary alkyl iodide electrophiles. Preliminary mechanistic experiments corroborate a hypothetical catalytic mechanism consisting of co-dependent cycles wherein the Cu-carbene co-catalyst engages in transmetallation to generate an organocopper nucleophile, while the Mn-carbonyl co-catalyst activates the alkyl halide electrophile by single-electron transfer and then undergoes reversible carbonylation to generate an acylmanganese electrophile. The two cycles then intersect with a heterobimetallic, product-releasing C-C coupling step.

Palladium and visible-light mediated carbonylative Suzuki-Miyaura coupling of unactivated alkyl halides and aryl boronic acids.

Herein, a simple and efficient method for the palladium-catalyzed carbonylation of aryl boronic acids with unactivated alkyl iodides and bromides under visible-light irradiation, ambient temperature and low CO-pressure is presented. Notably, the procedure uses readily available equipment and an inexpensive palladium catalyst to generate the key alkyl radical intermediate. These mild conditions enabled the synthesis of a range of functionalized aryl alkyl ketones including the antipsychotic drug, melperone.

Carbonylative Suzuki–Miyaura coupling catalyzed by palladium supported on aminopropyl polymethylsiloxane microspheres under atmospheric pressure of CO

Carbonylative Suzuki–Miyaura cross-coupling reactions of various aryl iodides with phenylboronic acids were catalyzed by palladium supported on amino-modified silica microspheres. Reactions performed with a very low concentration of Pd, under the atmospheric pressure of CO, led to high/moderate yields of multiple benzophenones.

Iron-catalyzed carbonylation of aryl halides with arylborons using stoichiometric chloroform as the carbon monoxide source

The highly effective iron-catalyzed carbonylative Suzuki–Miyaura coupling using stoichiometric chloroform as the CO precursor has been developed.

ChemInform Abstract: Palladacycle‐Catalyzed Carbonylative Suzuki—Miyaura Coupling with High Turnover Number and Turnover Frequency.

This work reports the carbonylative Suzuki-Miyaura coupling of aryl iodides catalyzed by palladacycles. More importantly, the palladacycles have been used to generate high turnover numbers (TON's) and turnover frequencies (TOF's). A range of aryl iodides can be coupled with arylboronic acids, generating TON's in the range of 10(6) to 10(7) and TOF's in the range of 10(5) to 10(6) h(-1). Comparison of the palladacycles with a conventional palladium source shows their superiority in generating high TON's and TOF's.

ChemInform Abstract: Synthesis of Aromatic β‐Keto Esters via a Carbonylative Suzuki—Miyaura Coupling Reaction of α‐Iodo Esters with Arylboronic Acids.

AbstractA radical mechanism is proposed.