CO Surrogate Research Articles

Three-Component Pd-Catalyzed N-Acylation of Amino Acid Esters Using Mo(CO)6 as a CO Surrogate

Three-Component Pd-Catalyzed N-Acylation of Amino Acid Esters Using Mo(CO)6 as a CO Surrogate

Pd‐catalyzed Three‐component Cross‐coupling of Arylhydrazides with Arylboronic Acids and TFBen: Facile Access to Diaryl Ketones via Denitrogenative Carbonylation

AbstractCarbonylation with CO surrogates is one of the most common methods for introduction of carbonyl groups in ketone synthesis. However, arylhydrazides have not been used as an aryl source in this denitrogenative method even though they are cheap and accessible. Here, we report development of palladium catalysis for the three‐component reactions of arylboronic acids, CO‐surrogates (benzene‐1,3,5‐triyl triformate), and arylhydrazides under oxygen conditions to produce diaryl ketones. (Hetero)arylhydrazides, as well as (hetero)arylboronic acids are suitable reaction partners, and good functional group compatibility was achieved. This method could be used for streamlined synthesis of diaryl ketones, ketoprofen and fenofibrate.

Carbon monoxide surrogates for palladium-catalyzed Suzuki-Miyaura and Sonogashira carbonylative cross-coupling reactions

Palladium-catalyzed Suzuki-Miyaura and Sonogashira reactions are probably the best methods to create new sp2-sp2 and sp2-sp chemical bonds starting from aryl halides and aryl boronic acids or terminal alkynes. These cross-couplings are generally promoted by a palladium-based catalyst and due to their potentialities, they have been deeply investigated. In particular, the carbonylative version of this reactions is widely used for the synthesis of conjugated diaryl and alkynyl ketones, biologically active compounds, and important building blocks for the synthesis of pharmaceuticals, and organic materials. The insertion of a carbon monoxide molecule is generally achieved by means of high pressure of CO but nowadays the severe toxicity of this gas has led to the development of CO surrogates which must be non-toxic and easy to handle. In this context, the aim of this review is to give a detailed comprehensive overview of the scientific literature regarding carbonylative Suzuki-Miyaura and Sonogashira reactions performed employing a CO source. The content of this review will be divided into two main chapters according to the different approach to CO generation, i.e., -in situ and ex situ technique. For each chapter, a systematic analysis of the nature of the CO surrogate will be reported.

Use of Formic Acid as a CO Surrogate for the Reduction of Nitroarenes in the Presence of Dienes: A Two‐Step Synthesis of N‐Arylpyrroles via 1,2‐Oxazines

AbstractFormic acid, activated by acetic anhydride and a base, was employed as a CO surrogate to deoxygenate nitroarenes to nitrosoarenes, a reaction catalyzed by a palladium/phenanthroline complex in the homogeneous phase. Nitrosoarenes were trapped by conjugated dienes to give 3,6‐dihydro‐2H‐[1,2]‐oxazines. The latter were then transformed into N‐arylpyrroles employing CuCl as the catalyst. The reaction was designed to give the best results for pyrroles lacking any substituent in the 2 and 5 positions, which are difficult to produce employing most pyrrole syntheses.

Palladium‐Catalyzed Carbonylation of Multifunctionalized Substituted Alkynes to Quinolinone Derivatives under Mild Conditions†

Comprehensive SummaryA highly selective palladium‐catalyzed carbonylation of 2‐alkynylanilines bearing an amide moiety to condensed six‐membered heterocyclic structures has been developed under mild conditions (room temperature and atmospheric pressure of CO). The carbonylative protocol is also compatible with CO surrogates, such as benzene‐1,3,5‐triyl triformate (TFBen) or the newly developed calix[6]arenes functionalized with six formate groups (CLX[6]CO), which are both capable to release CO in situ. A series of tricyclic fused heterocycles containing the important oxazino‐quinolinone scaffold have been selectively obtained (only the 6‐endo‐dig cyclization mode has been observed) in good to excellent yields (up to 99%).

Palladium-catalyzed carbonylative synthesis of carboxamide substituted 2-pynones from methyl enynoates and nitroarenes

A palladium-catalyzed carbonylative synthesis of carboxamide substituted 2-pynones from methyl enynoates and nitroarenes has been developed. With nitroarenes as the nitrogen sources, and Mo(CO)6 as both CO surrogate and reductant, a wide range of carboxamide substituted 2-pynones were obtained in moderate to high yields with quite high functional group compatibility. Moreover, the late-stage modifications of natural molecules was also achieved.

Ni/Al2O3: Catalyzed Carbonylative Homocoupling of Aryl Iodides for the Synthesis of Symmetrical Diaryl Ketone Using Co2(CO)8 as CO Surrogate

Ni/Al2O3: Catalyzed Carbonylative Homocoupling of Aryl Iodides for the Synthesis of Symmetrical Diaryl Ketone Using Co2(CO)8 as CO Surrogate

Carbonylative Self-Coupling of Aryl Boronic Acids Using a Confined Pd Catalyst within Melamine Dendron and Fibrous Nano-Silica: A CO Surrogate Approach.

Development of heterogeneous catalysts with tunable activity and selectivity has posed a persistent challenge. This study addresses this challenge by fabricating a hybrid environment through the combination of mesoporous silica and N-rich melamine dendron via covalent grafting, allowing for controllable growth and encapsulation of Pd NPs. This catalyst presented an excellent catalytic activity for the oxidative carbonylative self-coupling of aryl boronic acids to afford symmetric biaryl ketones using N-formyl saccharin as a sustainable solid CO source and Cu as a co-catalyst.

Effective Synthesis of 4-Quinolones by Reductive Cyclization of 2'-Nitrochalcones Using Formic Acid as a CO Surrogate.

4-Quinolones are the structural elements of many pharmaceutically active compounds. Although several approaches are known for their synthesis, the introduction of an aryl ring in position 2 is problematic with most of them. The reductive cyclization of o-nitrochalcones by pressurized CO, catalyzed by ruthenium or palladium complexes, has been previously reported to be a viable synthetic strategy for this aim, but the need for pressurized CO lines and autoclaves has prevented its widespread use. In this paper, we describe the use of the formic acid/acetic anhydride mixture as a CO surrogate, which allows us to perform the reaction in a cheap and commercially available thick-walled glass tube without adding any gaseous reagent. The obtained yields are often high and compare favorably with those previously reported by the use of pressurized CO. The procedure was applied to a three-step synthesis from commercially available and cheap reagents of the alkaloid Graveoline.

Nickel-Catalyzed Highly Selective Reductive Carbonylation Using Oxalyl Chloride as the Carbonyl Source

Nickel-catalyzed carbonylative cross-electrophile coupling which emerges as a powerful, efficient, and low-cost method for constructing challenging carbonyl derivatives has attracted increasing attention of organic chemists. To avoid the generation of a poisonous, volatile, and inert nickel carbonyl complex, it is critical to develop an efficient, cheap, and easily available CO surrogate. Oxalyl chloride, a cheap commercially available chemical, is one of the most versatile organic reagents used in chemical reactions. In this work, high chemoselectivity can be achieved with a 1:1:1 ratio of Ar–I to alkyl-I to oxalyl chloride. A wide range of alkyl aryl ketones which present an important class of molecules in synthetic and medicinal chemistry are accessed from alkyl halides, aryl iodides, under mild conditions. Primary and secondary alkyl iodides were suitable substrates. Various functional groups were well tolerated, affording up to 90% yields. This protocol was also used in the derivatization of natural products and drug molecules. Mechanistic investigation indicates that the reaction of Zn and oxalyl chloride under mild reaction conditions could release CO slowly. This knowledge should be useful for the further development of multicomponent carbonylative cross-coupling reactions.

Direct Access to α,β-Alkynylamides via Pd-Catalyzed Carbonylation of Terminal Alkynes with Amines Using Chloroform as the CO Surrogate.

We describe the first-time use of a palladium-di(1-adamantyl)-n-butylphosphine catalytic system for the synthesis of alk-2-ynamides from terminal alkynes via aminocarbonylation reaction. This method avoids the direct use of toxic CO gas by utilizing chloroform as an in situ CO source. The aminocarbonylation of both aromatic and aliphatic electron-rich alkyne nucleophiles is reported for the first time. The mild condition provides alk-2-ynamides within 50 min under microwave irradiation at 80 °C.

Selective Photocatalytic C–C Bond Cleavage of Lignin Models and Conversion to High-Value Chemical by Polyoxometalate Under a Mild Water-Based Environment

Selective bond cleavage using a photoredox reaction is a powerful technique in the chemical conversion of biomass such as lignin since it enables us to produce value-added aromatic compounds by controlling the activation of certain chemical bonds. Also, a water-based environment would be preferred for the sake of an eco-friendly reaction, additionally having the advantage of utilizing water-originated species such as •OH and H2O2. However, a direct cleavage of the C–C bond is still challenging due to the difficulties in tailoring redox potentials of catalysts relevant to covalent bond decoupling. Herein, we investigate a selective C–C bond cleavage of the β-O-4 lignin model compound using giant Keplerate polyoxometalates as photocatalysts. The redox potentials of photocatalysts are varied by changing metal compositions, and the correlation between redox potential and covalent bond decoupling is elucidated, probing each set of active radicals by HOMO and LUMOs. Especially, Mo132 shows a highly selective C–C bond cleavage with hydroxyl groups in the lignin model and produces phenyl formate─a effective CO surrogate for the synthesis of various organic compounds─as the main product (97.8% of product selectivity) in a water-based condition. Furthermore, Mo132 decomposes other aromatic polymer models, indicating the potential of photocatalytic C–C bond decoupling of polymers under a benign environment.

Shaping of Pd@UiO-66-biguanidine MOFs into composite beads with Cu-based CMC for synergistic catalysis towards CO-free carbonylative Sonogashira reaction

Integrating fine metal-organic framework (MOF) crystals within various materials to obtain configurable shapes with desired size and mechanical stability is an essential prerequisite for their potential applications on a large scale. In this work, a novel composite bead (Pd@UG/Cu@CMC), composed of Zr-based UiO-66-biguanidine-supported Pd MOFs (Pd@UG) embedded in the three-dimensional (3D) networks of Cu2+ crosslinked carboxymethylcellulose (Cu@CMC), has been successfully fabricated using a simple and straightforward metal ion crosslinking technology. The architecture of Pd@UG/Cu@CMC composite beads has been analyzed in detail using inductively coupled plasma atomic emission spectrometry (ICP-AES), Brunner−Emmet−Teller (BET) surface area analysis, Fourier transform infrared (FTIR) spectra, powder X-ray diffraction (PXRD), X-ray photoelectron spectroscopy (XPS), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy (EDX), elemental mapping, thermogravimetric analysis (TGA), derivative thermogravimetric analysis (DTG) tools. To validate the catalytic aptitude, the as-obtained Pd@UG/Cu@CMC beads were subsequently applied to carbonylative Sonogashira reactions using phenyl formate as a CO surrogate. The results showed that the catalyst had excellent catalytic performance over a broad scope of substrates under mild conditions and produced the desired products in moderate to excellent yields. The presence of Pd and Cu elements in the composite beads is essential, and the Cu played a dual role as both a crosslinker and co-catalyst in these reactions. The synergetic effect between Pd and Cu was conclusively evidenced by comparing them with Pd@UG, Cu@CMC, and their mixture, respectively. The composite beads retained their structure after seven consecutive runs with approximately 11% loss of catalytic efficiency. This work offers a promising route to shaping MOFs and provides suggestive insights for developing novel reusable bimetallic catalysts for high-performance synergistic catalysis.

Palladium-Catalyzed Carbonylation of Amines with Mo(CO)6 as the Carbonyl Source

Catalytic carbonylation of transition metals is widely used as an effective means to synthesize carbonyl-containing compounds. In this article, we introduce a method for the synthesis of N,N′-diphenyl urea and N-phenyl carbamate by transition-metal-catalyzed carbonylation. Here, we use Mo(CO)6 as a safe and stable carbonyl source to introduce the reaction to produce carbonylation products and achieve the selective formation of N,N′-diphenylurea and N-phenylcarbamate under mild conditions. Mechanistic investigations suggested that the reaction proceeded through sequential amine C–H bond activation, carbonyl insertion, nucleophilic attack, and oxidation of Pd(0) with Cu(OAc)2 to generate N-phenyl carbamate and N,N-diphenyl urea products. Moreover, the indenones obtained with Mo(CO)6 as a CO surrogate can be functionalized to form synthetic useful derivatives via an environmentally friendly way.

Phenyl Formate as a CO Surrogate for the Reductive Cyclization of Organic Nitro Compounds to Yield Different N-Heterocycles: No Need for Autoclaves and Pressurized Carbon Monoxide

The reductive cyclization of different organic nitro compounds by carbon monoxide, catalyzed by transition metal complexes, is a very efficient and clean strategy for the synthesis of many N-heterocycles. However, its use requires the use of autoclaves and pressurized CO lines. In this perspective, the authors will present the results obtained in their laboratories on the use of phenyl formate as a convenient CO surrogate, able to liberate carbon monoxide under the reaction conditions and allowing the use of a cheap glass pressure tube as a reaction vessel. In most cases, yields were better than those previously reported by the use of pressurized CO, proving that the use of CO surrogates can be a viable alternative to the gaseous reagent.

Intermolecular Pauson-Khand-Type Reaction of Vinyl Iodides with Alkynes and a CO Surrogate.

A strategy for the palladium-catalyzed intermolecular synthesis of polysubstituted cyclopentenones is reported. The three-component reaction utilizes vinyl iodides and internal alkynes to form the carbon framework of the cyclopentenone with Cr(CO)6 serving as an easy to handle, solid CO surrogate, and a hydrosilane as a hydride source. We demonstrate the scope of the reaction which includes a wide range of functional groups. The reaction is regioselective, with the use of linear or branched vinyl iodides resulting in the α- or β-substituted cyclopentenones, respectively. Further, we show that a two-step sequence from commercially available alkynes can be used to generate cyclopentenone products via formation of the vinyl iodide and subsequent Pauson-Khand-type reaction.

Direct formylation of phenols using difluorocarbene as a safe CO surrogate.

A convenient method to prepare aryl formates is reported herein that exploits difluorocarbene to serve as a CO surrogate. This reaction is proposed to occur through a sequential O-difluoromethylation of phenol, followed by α-C-F bond functionalization of the resulting aryl difluoromethyl ether intermediate by phenol or moisture through fluorosemiacetal or orthoformate intermediates. Late-stage modification of biologically and materially active compounds is demonstrated.

Palladium-catalyzed Heck-carbonylation of alkene-tethered carbamoyl chlorides with aryl formates.

We report a palladium-catalyzed Heck-carbonylation of alkene-tethered carbamoyl chlorides by utilizing aryl formates as convenient CO surrogates. One C-O and two C-C bonds are constructed to give diversiform esterified oxindoles/γ-lactams bearing an all-carbon quaternary stereocenter under gas-free conditions. This transformation features a wide substrate scope and good functional group tolerance and can be easily applied to late-stage functionalization.

A Pd-Sn heterobimetallic catalyst for carbonylative Suzuki, Sonogashira and aminocarbonylation reactions using chloroform as a CO surrogate.

Herein, we report a heterobimetallic Pd-Sn catalyst for the carbonylative Suzuki coupling, aminocarbonylation reaction, and carbonylative Sonogashira coupling of aryl halides with boronic acids, amines, and aromatic alkynes leading to a three-component coupling reaction using in situ generated carbon monoxide. Under the optimized reaction conditions, a variety of bisaryl ketones, amides, and aromatic ynones have been synthesized in moderate to good yields in a one-pot fashion. The reported catalyst has wide reaction scope with good functional group tolerance.

Catalytic Multicomponent Synthesis ofC‐Acyl Glycosides by Consecutive Cross‐Electrophile Couplings

AbstractC‐Acyl glycosides are versatile intermediates to natural products and medicinally relevant entities. Conventional cross‐coupling strategies to secure these molecules often relied on two‐component manifolds in which a glycosyl precursor is coupled with an acyl donor (pre‐synthesized or generated in situ) under transition metal or dual catalysis to forge a C−C bond. Here, we disclose a three‐component Ni‐catalyzed reductive regime that facilitates the chemoselective union of glycosyl halides, organoiodides and commercially available isobutyl chloroformate as a CO surrogate. The method tolerates multiple functionalities and the resulting products are obtained in high diastereoselectivities. Theoretical calculations provide a mechanistic rationale for the unexpectedly high chemoselectivity of sequential cross‐electrophile couplings. This approach enables the expeditious assembly of difficult‐to‐synthesizeC‐acyl glycosides, as well as late‐stage keto‐glycosylation of oligopeptides.