Catalytic Carboxylation Research Articles

Nickel-Catalyzed Atroposelective Carbo-Carboxylation of Alkynes with CO2: En Route to Axially Chiral Carboxylic Acids.

Precise synthesis of carboxylic acids via catalytic carboxylation with CO2 is highly appealing. Although considerable advancements have been achieved in difunctionalizing carboxylation of unsaturated hydrocarbons, the asymmetric variants are conspicuously underdeveloped, particularly in addressing axially chiral alkenes. Herein, we report the first catalytic atroposelective carboxylation of alkynes with CO2. A variety of valuable axially chiral carboxylic acids are obtained with good yields and high chemo-, regio-, E/Z and enantio-selectivities. Notably, an unexpected anti-selective carbo-carboxylation is observed in the sp2-hybrid carbo-electrophile-initiated reductive carboxylation of alkynes. Mechanistic studies including DFT calculation elucidate the origin of chiral induction and anti-selectivity in vinyl-carboxylation of alkynes.

Visible-Light Photoredox-Catalyzed Direct Carboxylation of Tertiary C(sp3)-H Bonds with CO2: Facile Synthesis of All-Carbon Quaternary Carboxylic Acids.

Direct carboxylation of C-H bonds with CO2 represents an attractive strategy to synthesize valuable carboxylic acids with high atom, step, and redox economy. Although great progress has been achieved in this field, catalytic carboxylation of tertiary C(sp3)-H bonds still remains challenging due to their inherent inertness and significant steric hindrance. Herein, we report a direct carboxylation of tertiary benzylic C(sp3)-H bonds with CO2 via visible-light photoredox catalysis. Various all-carbon quaternary carboxylic acids, which are of significant importance in medicinal chemistry, are successfully obtained with high yields. This direct carboxylation is characterized by good functional group tolerance, broad substrate scope, and mild operational conditions. Furthermore, our methodology enables the efficient and rapid synthesis of key drug or bioactive molecules, such as carbetapentane, caramiphen, and PRE-084 (σ1 receptor agonist), and facilitates various functionalizations of C(sp2)-H bonds using the directing ability of target carboxylic acids, thus highlighting its practical applications. Mechanistic studies indicate that a carbanion, which serves as the key intermediate to react with CO2, is catalytically generated via a single electron reduction of a benzylic radical through a consecutive photoinduced electron transfer process.

Efficient palladium-catalyzed electrocarboxylation enables late-stage carbon isotope labelling

Carbon isotope labelling of bioactive molecules is essential for accessing the pharmacokinetic and pharmacodynamic properties of new drug entities. Aryl carboxylic acids represent an important class of structural motifs ubiquitous in pharmaceutically active molecules and are ideal targets for the installation of a radioactive tag employing isotopically labelled CO2. However, direct isotope incorporation via the reported catalytic reductive carboxylation (CRC) of aryl electrophiles relies on excess CO2, which is incompatible with carbon-14 isotope incorporation. Furthermore, the application of some CRC reactions for late-stage carboxylation is limited because of the low tolerance of molecular complexity by the catalysts. Herein, we report the development of a practical and affordable Pd-catalysed electrocarboxylation setup. This approach enables the use of near-stoichiometric 14CO2 generated from the primary carbon-14 source Ba14CO3, facilitating late-stage and single-step carbon-14 labelling of pharmaceuticals and representative precursors. The proposed isotope-labelling protocol holds significant promise for immediate impact on drug development programmes.

Catalytic Regio- and Enantioselective Boracarboxylation of Arylalkenes with CO2 and Diboron.

Catalytic asymmetric carboxylation of readily available alkenes with CO2, an abundant and sustainable one-carbon building block, that gives access to value-added α-stereogenic carboxylic acids in an atom- and step-economic manner is highly attractive. However, it has remained a formidable challenge for the synthetic community. Here, the first example of Cu-catalyzed highly regio- and enantioselective boracarboxylation reaction on various arylalkenes with diboron under an atmospheric pressure of CO2 is described, which afforded a variety of chiral β-boron-functionalized α-aryl carboxylic acids with up to 87% yield and 97% ee under mild conditions. Importantly, α-substituted arylalkenes could also be subject to this protocol with excellent enantiopurities, thereby rendering an efficient approach for the generation of enantioenriched carboxylic acids with an α-chiral all-carbon quaternary center. Moreover, high functional group tolerance, scalable synthesis, and facile access to bioactive compounds, like (-)-scopolamine, (-)-anisodamine, and (-)-tropicamide, further demonstrated the synthetic utility of this strategy.

A copper-functionalized zirconium metal–organic framework for catalytic oxidative carboxylation of olefins and CO2

A Cu incorporation by post-metalation of a Zr-based metal–organic framework (MOF) produces a robustly bimetallic MOF that is suitable for selective CO2 adsorption and efficient conversion of CO2 and olefins into cyclic carbonates.

Nanosilver-decorated reduced graphene oxide for catalytic carboxylation of phenylacetylene with CO2

Nanosilver/reduced graphene oxide (AgNPs/rGO) nanocomposite by the green synthesis route was investigated using urea as a green reductor. The characterization of the AgNPs/rGO was confirmed by UV–Vis spectroscopy, FT-IR, XRD, Raman Spectroscopy, FE-SEM, Energy Dispersive X-ray (EDX), and TEM. The characterization result showed that the AgNPs/rGO was successfully synthesized by green reduction using urea, and the AgNPs were well-spread on the surface of the rGO. AgNPs/rGO nanocomposite was used as a catalyst towards the synthesize of phenylpropiolic acid from phenylacetylene carboxylation with CO2. The difference in the base used and reaction temperature influenced the carboxylation of phenylacetylene with CO2. The nanocomposite shows excellent selectivity towards phenylpropiolic acid. The highest conversion was obtained from the reaction using Na2CO3 at the temperature of 50 °C. Phenylpropiolic acid was formed as a major product with a high selectivity of 99.5%. The reusability of AgNPs/rGO nanocomposite as a carboxylation catalyst maintained an excellent selectivity above 99% even after third cycle.

Enhanced Lewis basicity of ZIF-8 from metal incorporation (Mg, Cu, or Ce) for glycerol carboxylation using CO2 as a feedstock

Herein, Mg, Ce, and Cu were incorporated into ZIF-8 to improve its Lewis basicity for glycerol carboxylation. Upon metal incorporation, the Ce- and Cu-incorporated ZIF-8 remained structurally intact with slightly increased Lewis basicity, whereas the Mg-incorporated ZIF-8 exhibited a more perturbed structure containing additional exposed N atoms and metal sites (Zn and Mg). The improved Lewis basicity facilitated the increased glycerol conversion of the Mg-incorporated ZIF-8 and its yield of glycerol carbonate in the presence of CH3CN as a homogeneous dehydrating agent. Using NaHCO3 as the heterogeneous dehydrating agent, a much higher selectivity (90%) was obtained over Mg-incorporated ZIF-8 compared to that of CH3CN (∼60% higher), attributed to a high water sorption capability of NaHCO3 that inhibits side reactions. The heterogeneity of NaHCO3 enables efficient recycling (>3 cycles) for repeated catalytic glycerol carboxylation. The results suggested that metal incorporation is an effective and facile approach to improve ZIF-8 Lewis basicity, combined with heterogeneous NaHCO3 as the dehydrating agent, which is beneficial for glycerol carboxylation using CO2 as a feedstock.

Immobilized Phosphoenolpyruvate Carboxylase Beads for Catalytic Carboxylation in Carbon Dioxide-Containing Gas–Liquid Flow

Phosphoenolpyruvate carboxylase (PEPC) catalyzes the Mg2+-dependent carboxylation reaction in aqueous phase with a carbon source. Performing enzymatic reactions in a bioreactor with gas–liquid contacting is challenging because proteins potentially undergo conformational change at the gas–liquid interface. In the present work, immobilized phosphoenolpyruvate carboxylase polystyrene beads (PEPC-PSBs) were prepared and applied to catalyze the carboxylation of phosphoenolpyruvate (PEP) producing oxaloacetate (OAA) in an external loop airlift bubble column (ELBC). For a typical reaction, ELBC was charged with 10 mL of a 0.2 M potassium phosphate buffer solution (pH = 7.5) initially containing 3.1 mM PEP and 9.7 mM MgSO4. When ELBC was operated at 25 °C with 20 PEPC-PSBs ([PEPC] = 2.0 μg/mL) by continuously introducing CO2 gas bubbles at the superficial gas velocity of 1.0 cm/s, the conversion of PEP of 77% was obtained at the reaction time of 300 min. After the reaction, PEPC-PSBs could be recovered from the reaction mixture followed by washing for reuse. PEPC-PSBs were storable at 4 °C and physically robust enough for handling. The catalytic activity of PEPC-PSBs was observed for the total reaction time of 900–1080 min in the gas–liquid flow. On the other hand, no detectable amount of OAA was produced with free PEPC in ELBC operated under the comparable condition to the PEPC-PSB-catalyzed reaction. Adsorption of free PEPC to CO2 gas bubbles was indicated to cause a rapid decrease in the concentration of biologically active PEPC in ELBC. The polystyrene beads with rough surface were suggested to offer an environment for the immobilized enzyme to stably catalyze the prolonged carboxylation of PEP with continuously supplied CO2-containing gas bubbles.

One-pot synthesis of cyclic carbonates from olefins and CO2 catalyzed by silica-supported imidazolium hydrogen carbonate ionic liquids

The direct synthesis of cyclic carbonates by catalytic oxidative carboxylation of olefins with CO2 has become an essential topic, but the development of highly active metal- and halogen-free heterogeneous single catalysts is still a huge challenge. Herein, a series of [Im][HCO3]@SBA-15 supported ionic liquids (SILs) catalysts are prepared by using anion exchange and solvent-free mehcanochemical grafting strategies for the direct synthesis of cyclic carbonates from olefins and CO2. As-prepared [Im][HCO3]@SBA-15 catalysts exhibit excellent catalytic activity and selectivity for the one-pot synthesis of cyclic carbonates from various olefins and CO2 under metal- and halogen-free conditions, providing moderate to excellent yields of cyclic carbonates. Furthermore, the catalysts can be easily regenerated at least five times without significant loss of catalytic activity, exhibiting excellent reusability and stability. This work presents an efficient and green method for the design and preparation of SILs catalysts for CO2 conversion.

Catalytic Carboxylation of Terminal Alkynes with Copper(I) Azothioformamide Complexes

Redox-active azothioformamide (ATF) ligands produce coordination complexes with Cu(I) salts. A series of monosubstituted ligands were used to synthesize Cu(I) complexes and investigated for the catalytic insertion of carbon dioxide into terminal alkynes. The optimal catalytic conditions were found using phenylacetylene with 4 mol % of a halogen-bridged (μ-I)-para-substituted [(p-MeOATF-Cu(I)I)]2 dimer with 3 equiv of Cs2CO3 as the base in dimethyl sulfoxide under 1 atm of CO2 at 40 °C for 24 h, followed by treatment with HCl. A variety of aryl and alkyl substrates were evaluated giving yields from 47 to 99%. The reaction was computationally deconstructed, and a series of likely intermediates and associated energies are provided along with a proposed mechanism. Additionally, it was found that the conditions were suitable for one-pot esterification.

The Al-Containing Silicates Modified with Organic Ligands and SnO2 Nanoparticles for Catalytic Baeyer-Villiger Oxidation and Aerobic Carboxylation of Carbonyl Compounds.

The Baeyer-Villiger Oxidation (BVO) of ketones and aldehydes produce lactones and formates, while aerobic carboxylation of aldehydes manufactures carboxylic acids, both having high added value. This work prepared a series of Al-containing silicates modified with organic ligands and SnO2 nanoparticles, which were then employed as catalyst in BVO and carboxylation. Characterizations revealed the morphology of the synthesized catalyst was changed from micron-sized thin sheets to smaller blocks, and then to uniform nanoparticles (size of 50 nm) having the doped SnO2 nanoparticles with a size of 29 nm. All catalysts showed high BET surface areas featuring silt-like mesopores. In determining the priority of BVO and carboxylation, an influence evaluation of the parameters showed the order to be substrate > oxidant > solvent > catalyst. Cyclic aliphatic ketones were suitable for BVO, but linear aliphatic and aromatic aldehydes for carboxylation. Coordination of (S)-binaphthol or doping of Sn into catalyst showed little influence on BVO under m-CPBA, but the Sn-doped catalyst largely increased BVO under (NH4)2S2O8 and H2O2. Calculations revealed that the catalyst containing both Al and Sn could give BVO intermediates lower energies than the Sn-beta zeolite model. The present system exhibited merits including wider substrate scope, innocuous catalytic metal, greener oxidant, as well as lower catalyst cost.

Recent progress in reductive carboxylation of C-O bonds with CO2.

Transformation of carbon dioxide (CO2) into value-added organic compounds has attracted increasing interest of scientific community in the last few decades, not only because CO2 is the primary greenhouse gas that drives global climate change and ocean acidification, but also because it has been regarded as a plentiful, nontoxic, nonflammable and renewable one-carbon (C1) feedstock. Among the various CO2-conversion processes, carboxylation reactions represent one of the most beautiful and attractive research topics in the field, since it offers the possibility for the construction of synthetically and biologically important carboxylic acids from various easily accessible (pseudo)halides, organosilicon, and organoboron compounds. The purpose of this review is to summarize the available literature on deoxygenative carboxylation of alcohols and their derivatives utilizing CO2 as a carboxylative reagent. Depending on the C-O compounds employed, the paper is divided into five major sections. The direct dehydroxylative carboxylation of free alcohols is discussed first. This is followed by reductive carboxylation of carboxylates, triflates, and tosylates. In the final section, the only reported example on catalytic carboxylation of fluorosulfates will be covered. Notably, special attention has been paid on the mechanistic aspects of the reactions that may provide new insights into catalyst improvement and development, which currently mainly relies on the use of transition metal catalysts.

Trichloromethyl Carbanion in Aqueous Micelles: Mechanistic Insights and Access to Carboxylic Acids from (Hetero)aryl Halides

While suppressing the decomposition of trichloromethyl carbanions (generated from CHCl3 using the LiOH base) to carbon monoxide and their participation in transmetallation and reductive elimination steps of cross-coupling’s catalytic cycle, a micelle-enabled catalytic carboxylation of (hetero)aryl halides is developed. The aqueous micelles play a crucial role in stabilizing both the highly reactive trichloromethyl carbanion and the single-metal atom catalyst to facilitate the desired reaction pathway efficiently. Comprehensive mechanistic analyses, including kinetic studies in the presence of trichloromethyl carbanion or carbon monoxide, H/D exchange via trichloromethyl anion, and mass spectrometric analysis of reaction intermediates, support a carbanion pathway. Simultaneously, the scope of this method was demonstrated over 40 substrates signifying broad functional and protecting group tolerance. This methodology was applied to the synthesis of isotopically enriched carboxylic acids using simple 18OH2 and/or 13CHCl3-labeled precursors.

Catalytic Umpolung Carboxylation of π-Allylpalladium Species with Carbon Dioxide

Catalytic Umpolung Carboxylation of π-Allylpalladium Species with Carbon Dioxide

Heterogeneous catalytic carboxylation of terminal alkynes with CO2 over a copper(II)-based metal-organic framework catalyst

Developing efficient, inexpensive and robust heterogeneous catalysts for CO2 conversion is greatly important. In this study, a new stable copper(II)-based metal-organic framework [Cu(Fbtx)2Br2]n (denoted as CZU-7, CCDC-2165700, Fbtx = 1,4-bis(1,2,4-triazole-1-ylmethyl)-2,3,5,6-tetrafluorobenzene) was synthesized via a facile and fast microwave heating method. CZU-7 exhibits a two-dimensional layer structure with the 44-sql topology. This material was demonstrated to be an efficient heterogeneous catalyst for the direct carboxylation of 1-ethynylbenzene with CO2, and various propiolic acids were synthesized in moderate to good yields under optimized reaction conditions. Moreover, the catalyst could be easily recovered and reused five times without significant loss of catalytic activity.

Factors Governing the Catalytic Insertion of CO2 into Arenes - A DFT Case Study for Pd and Pt Phosphane Sulfonamido Complexes.

The potential of Pd/Pt complexes for catalytic carboxylation of arenes with CO2 is investigated by means of computational chemistry. Recently we reported that the bis[(2‐methoxyphenyl)phosphino]‐benzenesulfonamido palladium complex 1 inserts CO2 reversibly in its Pd−C(aryl) bond generating carboxylato complex 2. In the present work we study how geometric and electronic factors of various ligands and substrates influence the overall activation barrier (energy span, ES) of a potential catalytic cycle for arene carboxylation comprising this elementary step. The tendency of the key intermediates to dimerize and thus deactivating the potential catalysts is examined as well as the role of the base, which inevitably is needed to stabilize the reaction product. We show that Pd and Pt complexes I(Pd)‐L16‐S1 and I(Pt)‐L16‐S1 do not dimerize, enable the computation of complete catalytic cycles, and show interestingly low ES values of 26.8 and 24.5 kcal/mol, respectively.

Nickel-catalyzed electrochemical carboxylation of unactivated aryl and alkyl halides with CO2

Electrochemical catalytic reductive cross couplings are powerful and sustainable methods to construct C−C bonds by using electron as the clean reductant. However, activated substrates are used in most cases. Herein, we report a general and practical electro-reductive Ni-catalytic system, realizing the electrocatalytic carboxylation of unactivated aryl chlorides and alkyl bromides with CO2. A variety of unactivated aryl bromides, iodides and sulfonates can also undergo such a reaction smoothly. Notably, we also realize the catalytic electrochemical carboxylation of aryl (pseudo)halides with CO2 avoiding the use of sacrificial electrodes. Moreover, this sustainable and economic strategy with electron as the clean reductant features mild conditions, inexpensive catalyst, safe and cheap electrodes, good functional group tolerance and broad substrate scope. Mechanistic investigations indicate that the reaction might proceed via oxidative addition of aryl halides to Ni(0) complex, the reduction of aryl-Ni(II) adduct to the Ni(I) species and following carboxylation with CO2.

A relay catalysis strategy for enantioselective nickel-catalyzed migratory hydroarylation forming chiral α-aryl alkylboronates

A relay catalysis strategy for enantioselective nickel-catalyzed migratory hydroarylation forming chiral α-aryl alkylboronates

Nickel-Catalyzed Reductive Carboxylation and Amidation Reactions.

The ubiquity and importance of carboxylic acids and amides in peptides, pharmaceuticals, agrochemicals, and synthetic materials has challenged chemists to design de novo catalytic carboxylation and amidation protocols. They represent a powerful alternative to canonical oxidation of alcohols and aldehydes, hydrolysis of nitriles, transamidation reactions, or condensation techniques for the synthesis of these functional groups. Among various scenarios, the recent years have witnessed considerable advances in Ni-catalyzed reductive carboxylation and amidation reactions utilizing carbon dioxide and isocyanate counterparts. This Account aims to highlight the progress made in this arena with a historical perspective, with particular emphasis on the methodologies that have emanated from our laboratories without losing sight of the underlying principles by which these reactions operate, with the ultimate goal of allowing the transition from comprehension to prediction in this exciting field.Unlike the utilization of conventional polar yet highly reactive organometallic reagents in carboxylation or amidation reactions, the utilization of nickel catalysts has allowed the use of carbon dioxide and isocyanates with less reactive and less-polarized counterparts for the formations of carboxylic acids and amides. These less reactive groups include organic halides and pseudohalides (i.e., alkyl bromides and chlorides, esters, alcohols, and ammonium salts), unsaturated hydrocarbons (i.e., alkynes, styrenes, unactivated alkenes, and dienes) or even C-H bonds, where forging the targeted C-C bond at previously unfunctionalized C-H linkages was possible, thus giving access to densely functionalized compounds that would be difficult to access otherwise. The C-H functionalization includes chain-walking scenarios, where subtle changes in the ligand and reaction conditions marked the selectivity of the transformations, and reactions via a [1,4]-Ni shift, where selective carboxylation in aromatic rings could be achieved. Conceptuality and practicality aside, these transformations have even offered the possibility of modulating and dictating the site-selectivity pattern, thus providing not only new vistas when controlling the selectivity of bond-forming reactions at specific sites within the side chain but also new knowledge in retrosynthetic analysis when accessing carboxylic acids and amide backbones. Importantly, these techniques have shown to be particularly suited for the preparation of isotopically labeled molecules when using 13CO2 or even 14CO2, thus becoming a useful endeavor in the drug discovery pipeline. Although mechanistic understanding at the molecular level still constitutes the "Achilles heel" of these transformations, the recent empirical discoveries and the rapid adoption of these protocols by the community augurs well for the widespread utilization of reductive carboxylation and amidation reactions in both academic and industrial laboratories.

Visible-light photoredox-catalyzed selective carboxylation of C(sp3)−F bonds with CO2

Visible-light photoredox-catalyzed selective carboxylation of C(sp3)−F bonds with CO2