CO Surrogate Research Articles

Furfural: An Efficient Platform Molecule as a CO Surrogate in Palladium Catalysed Synthesis of α, β‐Alkynylamides

AbstractBiomass‐derived furfural was used as a CO surrogate for the first time in the oxidative N‐dealkylation/carbonylation of various aliphatic and cyclic tertiary amines with terminal alkynes to produce alk‐2‐ynamides. This reaction employed O2 as an ideal oxidising agent and used a Pd/C catalyst with KI as an additive in a base free and ligand free condition. Notably, the selective sp3 C−N bond cleavage of tertiary amines led to its potential application as an amine source. The typical and simple route provides another option for producing a broad variety of alk‐2‐ynamide derivatives in environmentally friendly and efficient way under mild conditions. This method also displays notable reusability.

Iodoaniline Dependent Formation of N‐Aroylguanidines versus 2‐Aminoquinazolinones from Palladium(0) Catalysed Aminocarbonylation of N‐Arylguanidines

Abstract A family of N,N´‐diaryl‐N″‐(pyridine‐2‐ylmethyl)guanidines (B) were prepared in 70%−92% yields and subjected to palladium(0) catalyzed aminocarbonylation reactions with aryl iodides using CsOH/CHCl3 mixture as CO surrogate to afford the corresponding N‐aroylguanidines (C) in 70%−93% yields. A gram scale synthesis was reported for a representative example. When the aforementioned reaction was carried out with 2‐iodoaniline as an electrophile, either a mixture of two distinct 2‐aminoquinazolinones (D and E) or one of these 2‐aminoquinazolinones are formed. The scope of guanidines and aryl iodides were explored for both of the above‐mentioned reactions. The role of directing group in the substrates upon the successful aminocarbonylation of guanidines, B is outlined. When the ‐C(O)Ar unit in N‐aroylguanidines contain 2‐aminophenyl unit, a spontaneous cyclisation occurs to afford D or E or a mixture of both. The reactions of a pair of N‐aroylguanidines, C with PhI(OAc)2 afforded 2‐aminobenzimidazoles, T with unanticipated core. Plausible mechanisms of formation of C, D, E and T are outlined.

Palladium-catalyzed difluorocarbene transfer enables access to enantioenriched chiral spirooxindoles

AbstractWe disclose herein an unprecedented Pd-catalyzed difluorocarbene transfer reaction, which assembles a series of structurally interesting chiral spiro ketones with generally over 90% ee. Commercially available BrCF2CO2K serves as the difluorocarbene precursor, which is harnessed as a user-friendly and safe carbonyl source in this transformation. Preliminary mechanistic studies exclude the formation of free CO in the reaction process, and importantly, we also find that BrCF2CO2K outcompete gaseous CO and several common CO surrogates in this asymmetric process. The reaction mechanism, including the in-situ progressive release of the difluorocarbene, the rapid migratory insertion of ArPd(II) = CF2 species, and subsequent defluorination hydrolysis by water to introduce the carbonyl group, accounts for the overall high efficiency and uniqueness. This work clearly showcases the advantage and potential of the difluorocarbene in synthesis and supplies a mechanistically distinct route for asymmetric carbonylative cyclization reactions.

Nickel-Catalyzed Cyclization/Thiocarbonylation of Alkene-Tethered indoles with sulfonyl Chlorides: Synthesis of Thioester-Substituted Indolo[2,1-a]isoquinolines

A novel and straightforward procedure for the synthesis of thioester-substituted indolo[2,1-a]isoquinolines has been established. The reaction proceed via nickel-catalyzed cyclization/thiocarbonylation from alkene-tethered indoles and sulfonyl chlorides. Very good compatibility toward a wide range of functional groups was observed, both aryl and alkyl sulfonyl chlorides were well tolerated. With Mo(CO)6 as a convenient and solid CO surrogate, and by using sulfonyl chloride as an abundant and cheap sulfur source, a variety of thioester-substituted indolo[2,1-a]isoquinolines were obtained in moderate to high yields.

Advancements in Palladium-Catalyzed formic acid Dehydrogenation: Greening carbon monoxide synthesis in synthetic organic chemistry

The diverse applications of carbon monoxide-containing compounds make the construction of the carbonylation scaffolds, thus attracts the interest of synthetic chemist for exploitation. This review comprehensively summarize the significant advancement of the Pd-catalyzed an efficient and mild carbonylative reactions, with an emphasis on approaches for the generation of carbon monoxide intermediate from formic acid that offers an opportunities to overcome obstacles in the pharmacuticals. Among the CO surrogates, formic acid are more cheaper and environmentally benign methods gained considerable attention with the emergence of newer methods and are advantageous in terms of their good availability, and ease of handling. We have summarized the recent development in carbonylation reactions using formic acid as a surrgoate from past decade. We believe that we discuss provide an overview regarding the the recent progress, challenges, opportunities and future outcomes in the area of the carbonylation chemistry using formic acid available as an Carbon monoxide source.

Cover Picture: An Electrocatalytic Cascade Reaction for the Synthesis of Ketones Using CO2 as a CO Surrogate (Angew. Chem. Int. Ed. 23/2024)

Cover Picture: An Electrocatalytic Cascade Reaction for the Synthesis of Ketones Using CO₂ as a CO Surrogate (Angew. Chem. Int. Ed. 23/2024)

Rhodium-Catalyzed C–H Carbonylation of Benzamides Using a CO Surrogate

Rhodium-Catalyzed C–H Carbonylation of Benzamides Using a CO Surrogate

Palladium‐Catalyzed Carbonylation of Aryl Sulfonium Salts with CO2 as a CO Surrogate

AbstractPalladium‐catalyzed carbonylation of aryl sulfonium salts with CO2 as a CO surrogate has been successfully developed via a one‐pot two‐step procedure. Thus, by merging thianthrenation and the carbonylation, site‐selective aromatic C−H carbonylation of a plethora of readily available arenes can be realized with CO2, providing access to a variety of structurally diverse and useful benzamides, esters and carboxylic acids. Simple operation, broad substrate scope, good functional group tolerance and mild reaction conditions are the attractive features of the method. Late‐stage functionalization of complex bioactive molecules as well as the precise synthesis of pharmaceuticals 1‐BCP and butoxycaine demonstrated the potential application of the established protocol.

Ni/C-catalyzed aminocarbonylation of aryl halides using DMF as an amine source and o-chlorophenyl formate as a CO surrogate and promoter

We developed Ni/C-catalyzed aminocarbonylation of aryl halide by utilizing DMF and o-chlorophenyl formate to produce tertiary amides. This reaction employed o-chlorophenyl formate (OCPF) as a CO source, and it also acts as a promoter for the selective tertiary amide synthesis. Even under ideal conditions, this newly established approach considerably reduces the generation of homo-coupled biaryl ketone and phenoxy carbonylation byproducts. This protocol shows remarkable activity towards a wide range of aryl halides containing electron-donating and electron-withdrawing functional groups. This methodology represents the moisture-sensitive ligand-free, co-catalyst-free, and heterogeneous recyclable catalyst. The Ni/C catalyst was utilized for up to five consecutive runs. The fresh and recycled Ni/C catalysts were characterized using several techniques, including TEM, SEM, EDX, XRD, and TGA analysis.

An Electrocatalytic Cascade Reaction for the Synthesis of Ketones Using CO2 as a CO Surrogate

AbstractThe construction of carbonyl compounds via carbonylation reactions using safe CO sources remains a long‐standing challenge to synthetic chemists. Herein, we propose a catalyst cascade Scheme in which CO2 is used as a CO surrogate in the carbonylation of benzyl chlorides. Our approach is based on the cooperation between two coexisting catalytic cycles: the CO2‐to‐CO electroreduction cycle promoted by [Fe(TPP)Cl] (TPP=meso‐tetraphenylporphyrin) and an electrochemical carbonylation cycle catalyzed by [Ni(bpy)Br2] (2,2′‐bipyridine). As a proof of concept, this protocol allows for the synthesis of symmetric ketones from good to excellent yields in an undivided cell with non‐sacrificial electrodes. The reaction can be directly scaled up to gram‐scale and operates effectively at a CO2 concentration of 10 %, demonstrating its robustness. Our mechanistic studies based on cyclic voltammetry, IR spectroelectrochemistry and Density Functional Theory calculations suggest a synergistic effect between the two catalysts. The CO produced from CO2 reduction is key in the formation of the [Ni(bpy)(CO)2], which is proposed as the catalytic intermediate responsible for the C−C bond formation in the carbonylation steps.

An Electrocatalytic Cascade Reaction for the Synthesis of Ketones Using CO2 as a CO Surrogate.

The construction of carbonyl compounds via carbonylation reactions using safe CO sources remains a long-standing challenge to synthetic chemists. Herein, we propose a catalyst cascade Scheme in which CO2 is used as a CO surrogate in the carbonylation of benzyl chlorides. Our approach is based on the cooperation between two coexisting catalytic cycles: the CO2-to-CO electroreduction cycle promoted by [Fe(TPP)Cl] (TPP=meso-tetraphenylporphyrin) and an electrochemical carbonylation cycle catalyzed by [Ni(bpy)Br2] (2,2'-bipyridine). As a proof of concept, this protocol allows for the synthesis of symmetric ketones from good to excellent yields in an undivided cell with non-sacrificial electrodes. The reaction can be directly scaled up to gram-scale and operates effectively at a CO2 concentration of 10 %, demonstrating its robustness. Our mechanistic studies based on cyclic voltammetry, IR spectroelectrochemistry and Density Functional Theory calculations suggest a synergistic effect between the two catalysts. The CO produced from CO2 reduction is key in the formation of the [Ni(bpy)(CO)2], which is proposed as the catalytic intermediate responsible for the C-C bond formation in the carbonylation steps.

First row transition metal catalyzed small molecule activation for sustainable organic transformation: Synergy between nature and chemist’s toolbox

In this review we have tried to present our view on the synergy between nature and chemists’ toolbox toward discovery of new reactions. Toward the search for new chemical reactivity, not only chemists learn from nature but nature’s evolutionary pathway perhaps has footprints of chemist’s innovative discoveries and beyond. Taking CO2 as a representative example of an abundant energy rich small molecule resource, we have tried to explore the probable strategies of activating the molecule using first row transition metal catalysts for sustainable organic transformation. Our study has tried to unfold nature’s strategy of CO2 activation and recycling which eventually motivated chemists toward discovery of new chemical reactions and further inspired to expand their toolbox for discovering new reactivities beyond the natural enzyme repertoire. The basic chemical CO2 activation strategy which have been focused in this review are using CO2 as a C1 building block in organic synthesis; catalytic reductive formylation and methylation of amines; carboxylation reactions via CO2 insertion. Additionally, carbonylation reactions with CO2 as CO surrogate has also been discussed. The focus of this review is to correlate nature’s chemical strategies with chemist’s approach to understand the concept involved in the chemical activation and utilization process of CO2 for unlocking new reaction paradigm, both for chemists’ and for nature’s catalytic repertoire.

Visible Light-Induced One-Pot Carbonylation of Alkyl Halides with Aryl Formates.

Described herein is the development of a visible-light-driven carbonylation of alkyl halides. The exploitation of visible light to activate Pd complexes and the use of formates to serve the dual role of a CO surrogate and a phenoxide source allow the preparation of esters in moderate to good yields. Its relatively mild reaction conditions and the ability to perform this transformation without direct handling of toxic CO gas provide a practical means to access esters from alkyl halides.

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs.

A sequential strategy to access 10,11-dihydro-5H-dibenzo[b,e][1,4]diazepinones (DBDAPs) is disclosed in this article through a palladium and copper-catalyzed amination (Buchwald-Hartwig (B-H) or Chan-Lam (C-L)) followed by a palladium-catalyzed intramolecular aminocarbonylation with Mo(CO)6 as CO surrogate (to avoid toxic CO handling) of readily available o-phenylenediamines and either 1,2-dibromobenzene or 2-bromophenylboronic acid. The 10,11-dihydro-5H-dibenzo[b,e][1,4]diazepinone could be synthezised in good yield using a sequential catalytic procedure, using both C-L and B-H approaches. Gratifingly, the use of the C-L reaction was more impressive, and afforded the dibenzodiazepinones in good yields (up to 45%; 2 steps) and much milder conditions using copper as the catalyst. The synthetic utility of this novel strategy was showcased by demonstrating a formal synthesis for the antipsychotic drug clozapine and to an anticancer triazole-DBDAP hybrid.

A Sustainable and Versatile Cellulose-based CO Surrogate for Carbonylative Reactions.

The highly toxic and flammable nature of CO lead to high handling demand for its use and storage, undoubtedly constricting its further academic exploration for carbonylative reactions in laboratory. Although many CO surrogates have been developed and applied in carbonylative reactions instead of CO gas, exploration of more versatile CO surrogates for diverse carbonylations is still highly desirable. Here we report a cellulose-based CO surrogate (cellulose-CO), which prepared from cheap and abundant cellulose through a simple and green process. The very mild and efficient CO release makes this reagent a highly competitive candidate for providing CO in carbonylation. This surrogate is compatible with a wide variety of functional groups in various carbonylative reactions due to the excellent compatibility of cellulose-CO. Moreover, the cellulose-CO exhibits excellent chemical stability which can be stored exposed to air for 12 months, making this CO surrogate a robust and general reagent in CO chemistry.

Photoinduced CO-releasing molecule (photoCORM) as an in situ CO surrogate for palladium-catalysed aminocarbonylation.

Herein, we show that a photoCORM behaves as a highly substrate-tolerant, photoactivable in situ CO surrogate, allowing the synthesis of variously functionalised amides including the biologically active compound Moclobemide by Pd-catalysed aminocarbonylation between aryl iodides and amines under mild conditions. This work should bring about a useful input to the field of carbonylative transformations.

A chemoselective hydroxycarbonylation and 13C-labeling of aryl diazonium salts using formic acid as the C-1 source.

We report a one-pot synthesis of aryl carboxylic acids utilizing HCOOH as a CO surrogate with low Pd-catalyst loading. This operationally simple and scalable method does not require use of a high-pressure reactor, two-chamber reaction vessel, phosphine ligand, or base and proceeds in a relatively short amount of time at ambient temperature. Notably, halides, including iodo and bromo groups, and nitro groups remain intact under these mild reaction conditions. This methodology has been successfully applied to synthesizing 13C-labeled aryl carboxylic acids with satisfactory yields.

Cross‐Linked Pseudopeptides via Pd‐Catalyzed Carbonylative Coupling of α‐Amino Acid Iodides with α‐Amino Acid Esters in the Presence of a CO Surrogate

AbstractWe report the synthesis of cross‐linked pseudopeptides through a palladium‐catalyzed carbonylative cross‐coupling reaction. The reaction involves the coupling of α‐amino acid iodides with α‐amino acid esters via in situ CO insertion to give pseudopeptides linked by the side chain of the electrophilic counterpart. The key features are the use of a sustainable in situ CO surrogate, simple non‐inert conditions, short reaction time, and broad substrate scope. Both amino acids and peptide iodides were utilized as coupling partners.

Recent Advances in Nickel Catalyzed Carbonylative Reactionsviathe Insertion of Carbon Monoxide†

Comprehensive SummaryCarbonyl compounds have attracted considerable attention due to their extensive applications in drug discovery. Furthermore, they are important synthetic intermediates for the construction of carbon‐carbon and carbon‐heteroatom bonds. Transition‐metal‐catalyzed carbonylation via the insertion of CO is one of the most efficient and straightforward strategies to access carbonyl compounds. However, most of the transition‐metal‐catalyzed carbonylative reactions require expensive and toxic noble‐metal catalysts. Therefore, there is a growing demand for the exploration of nickel‐catalyzed carbonylative reactions via the insertion of CO due to the earth abundance and low cost of nickel. Compared with the well‐established palladium‐catalyzed carbonylative reactions, nickel‐catalyzed analogous transformations have been relatively underdeveloped. This is primarily because CO strongly binds to nickel, often resulting in catalyst poisoning. In recent years, some research groups have focused on using CO surrogates or NN2pincer nickel catalyst to circumvent the formation of Ni(CO)4. Nickel‐catalyzed carbonylation has been applied in the construction of carbonyl‐containing compounds, such as ketones, carboxylic acids, thioesters, acyl chloride and carboxamides.

Cobalt(II)-Catalyzed Intermolecular Aminocarbonylation of Indoles with Amines.

A cobalt(II)-catalyzed C2-H carbonylation of indoles with amines toward indole-2-carboxamides has been developed. By employing Co(OAc)2·4H2O as an inexpensive catalyst and using benzene-1,3,5-triyl triformate (TFBen) as the CO surrogate, a variety of indole-2-carboxamide derivatives were produced in moderate to high yields. Additionally, several bioactive-molecule-related compounds can be applied as substrates, as well.