Regioselective Alkylative Carboxylation of Allenamides with Carbon Dioxide and Dialkylzinc Reagents Catalyzed by an N‐Heterocyclic Carbene–Copper Complex

The alkylative carboxylation of allenamide catalyzed by an N‐heterocyclic carbene (NHC)–copper(I) complex [(IPr)CuCl] with CO₂ and dialkylzinc reagents was investigated. The reaction of allenamides with dialkylzinc reagents (1.5 equiv) and CO₂ (1 atm.) proceeded smoothly in the presence of a catalytic quantity of [(IPr)CuCl] to afford (Z)‐α,β‐dehydro‐β‐amino acid esters in good yields. The reaction is regioselective, with the alkyl group introduced onto the less hindered γ‐carbon, and the carboxyl group introduced onto the β‐carbon atom of the allenamides. The first step of the reaction was alkylative zincation of the allenamides to give an alkenylzinc intermediate followed by nucleophilic addition to CO₂. A variety of cyclic and acyclic allenamides were found to be applicable to this transformation. Dialkylzinc reagents bearing β‐hydrogen atoms, such as Et₂Zn or Bu₂Zn, also gave the corresponding alkylative carboxylation products without β‐hydride elimination. The present methodology provides an easy route to alkyl‐substituted α,β‐dehydro‐β‐amino acid ester derivatives under mild reaction conditions with high regio‐ and stereoselectivtiy.     

Alkylative Carboxylation of Ynamides and Allenamides with Functionalized Alkylzinc Halides and Carbon Dioxide by a Copper Catalyst

The alkylative carboxylation of ynamides and allenamides with CO₂ and alkylzinc halides catalyzed by a copper catalyst was developed. A variety of alkylzinc halides bearing functional groups were used for this transformation to afford α,β-unsaturated carboxylic acids, which contain the α,β-dehydroamino acid skeleton, introducing the corresponding alkyl group and CO₂ across the carbon–carbon triple or double bond. This alkylative carboxylation formally consists of Cu-catalyzed carbozincation of ynamides or allenamides with alkylzinc halides and the subsequent nucleophilic carboxylation of the resulting alkenylzinc species with CO₂. This protocol would be a useful method for the synthesis of α,β-dehydroamino acid derivatives possessing a functionalized alkyl group due to the high regio- and stereoselectivity, simple one-pot procedure as well as the use of CO₂ as a starting material.     

Cu‐Catalyzed Formal Methylative and Hydrogenative Carboxylation of Alkynes with Carbon Dioxide: Efficient Synthesis of α,β‐Unsaturated Carboxylic Acids

The sequential hydroalumination or methylalumination of various alkynes catalyzed by different catalyst systems, such those based on Sc, Zr, and Ni complexes, and the subsequent carboxylation of the resulting alkenylaluminum species with CO₂ catalyzed by an N‐heterocyclic carbene (NHC)–copper catalyst have been examined in detail. The regio‐ and stereoselectivity of the overall reaction relied largely on the hydroalumination or methylalumination reactions, which significantly depended on the catalyst and alkyne substrates. The subsequent Cu‐catalyzed carboxylation proceeded with retention of the stereoconfiguration of the alkenylaluminum species. All the reactions could be carried out in one‐pot to afford efficiently a variety of α,β‐unsaturated carboxylic acids with well‐controlled configurations, which are difficult to construct by previously reported methods. This protocol could be practically useful and attractive because of its high regio‐ and stereoselectivity, simple one‐pot reaction operation, and the use of CO₂ as a starting material.     

Carboxylation Reactions with Carbon Dioxide Using N‐Heterocyclic Carbene‐Copper Catalysts

The development of versatile catalyst systems and new transformations for the utilization of carbon dioxide (CO₂) is of great interest and significance. This Personal Account reviews our studies on the exploration of the reactions of CO₂ with various substrates by the use of N‐heterocyclic carbene (NHC)‐copper catalysts. The carboxylation of organoboron compounds gave access to a wide range of carboxylic acids with excellent functional group tolerance. The C?H bond carboxylation with CO₂ emerged as a straightforward protocol for the preparation of a series of aromatic carboxylic esters and butenoates from simple substrates. The hydrosilylation of CO₂ with hydrosilanes provided an efficient method for the synthesis of silyl formate on gram scale. The hydrogenative or alkylative carboxylation of alkynes, ynamides and allenamides yielded useful α,β‐unsaturated carboxylic acids and α,β‐dehydro amino acid esters. The boracarboxylation of alkynes or aldehydes afforded the novel lithium cyclic boralactone or boracarbonate products, respectively. The NHC‐copper catalysts generally featured excellent functional group compatibility, broad substrate scope, high efficiency, and high regio‐ and stereoselectivity. The unique electronic and steric properties of the NHC‐copper units also enabled the isolation and structural characterization of some key intermediates for better understanding of the catalytic reaction mechanisms.     

二氧化碳与不饱和烃的还原羧化反应

过渡金属催化CO₂参与的不饱和烃还原羧化反应是合成羧酸及丙烯酸类化合物的重要途径, 具有重要的研究价值和工业应用潜力．过渡金属试剂与不饱和烃、CO₂生成稳定的金属杂环内酯或金属羧酸盐．还原剂能够与金属杂环内酯或金属羧酸盐发生转金属作用, 重新生成活泼催化剂, 从而实现催化剂的循环利用．本文总结了还原剂, 包括有机金属试剂、硅烷、硼烷、金属粉末、甲醇和氢气等在不饱和烃与CO₂的还原羧化反应中的应用, 并着重描述其反应特点和反应机理.     

Access to α‐Arylglycines by Umpolung Carboxylation of Aromatic Imines with Carbon Dioxide

A straightforward and transition‐metal‐free approach for the efficient synthesis of α‐arylglycine derivatives from aromatic imines and carbon dioxide was enabled by an umpolung carboxylation reaction. Various substituted diphenylmethimines underwent the carboxylation smoothly with carbon dioxide in the presence of potassium tert‐butoxide and 18‐crown‐6 to give the corresponding carboxylated products in good to high yields. Besides the enhancement of the solubility of potassium tert‐butoxide in THF, 18‐crown‐6 also plays key roles in suppressing the reverse protonation or 1, 3‐proton shift isomerization as well as by stabilizing the carboxylated intermediate.     

Highly Regioselective Palladium‐Catalyzed Carboxylation of Allylic Alcohols with CO2

Various allylic alcohols were carboxylated in the presence of a catalytic amount of PdCl₂ and PPh₃ using ZnEt₂ as a stoichiometric transmetalation agent under a CO₂ atmosphere (1 atm). This carboxylation proceeded in a highly regioselective manner to afford branched carboxylic acids predominantly. The β,γ‐unsaturated carboxylic acid thus obtained was successfully converted into an optically active γ‐butyrolactone, a known intermediate of (R)‐baclofen.     

The Renaissance of an Old Problem: Highly Regioselective Carboxylation of 2‐Alkynyl Bromides with Carbon Dioxide

A steric effect‐controlled, zinc‐mediated carboxylation of different 2‐alkynyl bromides under an atmospheric pressure of CO₂ has been developed by careful tuning of different reaction parameters, including the metal, solvent, temperature, and additive. 2‐Substituted 2,3‐allenoic acids were afforded from primary 2‐alkynyl bromides, whereas the carboxylation of secondary 2‐alkynyl bromides yielded 3‐alkynoic acids in decent yields. A rationale for the observed regioselectivity has been proposed.     

Efficient Conversion of Carbon Dioxide with Si‐Based Reducing Agents Catalyzed by Metal Complexes and Salts

Homogeneous metal complex and salt catalysts were developed for the reductive transformation of CO₂ with Si‐based reducing agents. Cu‐bisphosphine complexes were found to be excellent catalysts for the hydrosilylation of CO₂ with polymethylhydrosiloxane (PMHS). The Cu complexes also showed high catalytic activity and a wide substrate scope for formamide synthesis from amines, CO₂, and PMHS. Simple fluoride salts such as tetrabutylammonium fluoride acted as good catalysts for the reductive conversion of CO₂ to formic acid in the presence of hydrosilane, disilane, and metallic Si. Based on the kinetics, isotopic experiments, and in‐situ NMR measurements, the reaction mechanism for both catalyst systems, the Cu complex and the fluoride salt, have been proposed.     

Homogeneous Light‐Driven Catalytic Direct Carboxylation with CO2

Carbon dioxide is a ubiquitous and inexpensive one‐carbon source for chemical synthesis, and the efficient incorporation of CO₂ into organic molecules is of widespread research interest both for economic and ecological reasons. The methodologies to employ carbon dioxide as a single‐carbon unit to construct molecules relevant for agrochemical and pharmaceutical research include many elegant approaches, including asymmetric transformations. Even though remarkable achievements have been made in the field of light‐driven catalysis, especially photoredox catalysis, homogeneous light‐driven catalytic carboxylation by employing CO₂ as the key reagent has only become a subject of increasing attention in recent years. Therefore, this concise review will discuss the latest advances in this research area.     

Synthesis of Lithium Boracarbonate Ion Pairs by Copper‐Catalyzed Multi‐Component Coupling of Carbon Dioxide,Diboron, and Aldehydes

The catalytic selective multi‐component coupling of CO₂, bis(pinacolato)diboron, LiOtBu, and a wide range of aldehydes has been achieved for the first time by using an NHC‐copper catalyst. This transformation has efficiently afforded a series of novel lithium cyclic boracarbonate ion pair compounds in high yields from readily available starting materials. This protocol has not only provided a new catalytic process for the utilization of CO₂, but it has also constituted a novel route for the efficient synthesis of a new class of lithium borate compounds that might be of interest as potential electrolyte candidates for lithium ion batteries.     

N‐Heterocyclic Olefin–Carbon Dioxide and –Sulfur Dioxide Adducts: Structures and Interesting Reactivity Patterns

Depending on the amount of methanol present in solution, CO₂ adducts of N‐heterocyclic carbenes (NHCs) and N‐heterocyclic olefins (NHOs) have been found to be in fully reversible equilibrium with the corresponding methyl carbonate salts [EMIm][OCO₂Me] and [EMMIm][OCO₂Me]. The reactivity pattern of representative 1‐ethyl‐3‐methyl‐NHO–CO₂ adduct 4 has been investigated and compared with the corresponding NHC–CO₂ zwitterion: The protonation of 4 with HX led to the imidazolium salts [NHO–CO₂H][X], which underwent decarboxylation to [EMMIm][X] in the presence of nucleophilic catalysts. NHO–CO₂ zwitterion 4 can act as an efficient carboxylating agent towards CH acids such as acetonitrile. The [EMMIm] cyanoacetate and [EMMIm]₂ cyanomalonate salts formed exemplify the first C?C bond‐forming carboxylation reactions with NHO‐activated CO₂. The reaction of the free NHO with dimethyl carbonate selectively led to methoxycarbonylated NHO, which is a perfect precursor for the synthesis of functionalized ILs [NHO–CO₂Me][X]. The first NHO‐SO₂ adduct was synthesized and structurally characterized; it showed a similar reactivity pattern, which allowed the synthesis of imidazolium methyl sulfites upon reaction with methanol.     

Palladium‐Catalyzed Oxygenative Cross‐Coupling of Ynamides and Benzyl Bromides by Carbene Migratory Insertion

A palladium‐catalyzed oxygenative cross‐coupling of ynamides and benzyl bromides has been developed. After subsequent hydrogenation, α,α‐disubstituted amide derivatives were obtained in good yields. Migratory insertion of α‐oxo palladium carbene species, generated by intermolecular oxidation, is proposed as the key step in this reaction. The study demonstrates the potential of ynamides to serve as carbene precursors in palladium‐catalyzed C?C bond‐forming cross‐coupling reactions.     

Enantioselective CO2 Fixation Via a Heck-Coupling/Carboxylation Cascade Catalyzed by Nickel

A novel asymmetric nickel-based procedure has been developed in which CO₂ fixation is achieved as a second step of a truncated Heck coupling. For this, a new chiral ligand has been prepared and shown to achieve enantiomeric excesses up to 99 %. The overall process efficiently furnishes chiral 2,3-dihydrobenzofuran-3-ylacetic acids, an important class of bioactive products, from easy to prepare starting materials. A combined experimental and computational effort revealed the key steps of the catalytic cycle and suggested the unexpected participation of Ni(I) species in the coupling event.     

Electrochemically Activated Reaction of Benzoyl Halides with Carbon Dioxide

The electrochemical activation and carboxylation of benzoyl halides (benzoyl bromide, chloride, and fluoride) were studied. It was found that the yield of phenylglyoxylic acid increases from zero to 88% in the transition from benzoyl fluoride to the chloride and bromide. The effect of the nature of the halogen atom in the benzoyl halide and also the nature of the supporting electrolyte and the electrode material on the electrochemical reduction and carboxylation of benzoyl halides was studied.     

Cu‐Catalyzed Asymmetric Allylic Alkylation of Phosphonates and Phosphine Oxides with Grignard Reagents

An efficient and highly enantioselective copper‐catalyzed allylic alkylation of phosphonates and phosphine oxides with Grignard reagents and Taniaphos or phosphoramidites as chiral ligands is reported. Transformation of these products leads to a variety of new phosphorus‐containing chiral intermediates.