C1 Building Block Research Articles

Chemical fixation of CO2/CS2 to access iodoallenyl oxazolidinones and allenyl thiazolidine-thiones.

Constructing heterocyclic compounds by chemical fixation of CO2/CS2 as a C1 building block is a promising approach. An efficient and environmentally friendly synthetic approach has been developed using CO2/CS2 to prepare complicated allenyl heterocycles with high yields and diastereoselectivities in a metal-free manner under mild conditions. NIS promoted CO2 fixation and the cyclization reaction by exclusive 1,4-syn-addition of 1,3-enynes rather than 1,2-addition or 3,4-addition, while CS2 participated in unique 1,4-syn-hydrothiolation of 1,3-enynes to afford allenyl heterocycles with different reaction patterns.

Dynamics of carbene formation in the reaction of methane with the tantalum cation in the gas phase.

The controlled activation of methane has drawn significant attention throughout various disciplines over the last few decades. In gas-phase experiments, the use of model systems with reduced complexity compared to condensed-phase catalytic systems allows us to investigate the intrinsic reactivity of elementary reactions down to the atomic level. Methane is rather inert in chemical reactions, as the weakening or cleavage of a C-H bond is required to make use of methane as C1-building block. The simplest model system for transition-metal-based catalysts is a mono-atomic metal ion. Only a few atomic transition-metal cations activate methane at room temperature. One of the most efficient elements is tantalum, which forms a carbene and releases molecular hydrogen in the reaction with methane: Ta+ + CH4 → TaCH2+ + H2. The reaction takes place at room temperature due to efficient intersystem crossing from the quintet to the triplet surface, i.e., from the electronic ground state of the tantalum cation to the triplet ground state of the tantalum carbene. This multi-state reactivity is often seen for reactions involving transition-metal centres, but leads to their theoretical treatment being a challenge even today. Chemical reactions, or to be precise reactive collisions, are dynamic processes making their description even more of a challenge to experiment and theory alike. Experimental energy- and angle-differential cross sections allow us to probe the rearrangement of atoms during a reactive collision. By interpreting the scattering signatures, we gain insight into the atomistic mechanisms and can move beyond stationary descriptions. Here, we present a study combining collision energy dependent experimentally measured differential cross sections with ab initio calculations of the minimum energy pathway. Product ion velocity distributions were recorded using our crossed-beam velocity map imaging experiment dedicated to studying transition-metal ion molecule reactions. TaCH2+ velocity distributions reveal a significant degree of indirect dynamics. However, the scattering distributions also show signatures of rebound dynamics. We compare the present results to the oxygen transfer reaction between Ta+ and carbon dioxide, which we recently studied.

Assembly of (2×C2+C’2)×n Molecular Complexity Using a Sequence of Pt‐ and Pd‐Catalyzed Transformations with Calcium Carbide

AbstractConstructing molecular complexity from simple precursors stands as a cornerstone in contemporary organic synthesis. Systems harnessing easily accessible starting materials, which offer control over stereochemistry and support a modular assembly approach, are particularly in demand. In this research, we utilized calcium carbide, presenting a sustainable pathway to generate acetylene gas – a fundamental C2 building block. We performed a Pt‐facilitated linkage of two C2‐units sourced from two calcium carbide molecules to craft a conjugated C4 core with exceptional stereoselectivity. As a benchmark, we selected the synthesis of (E,E)‐1,4‐diiodobuta‐1,3‐diene, executing it in a two‐chamber reactor. Compartmentalization of the reactions across these chambers resulted in the desired product in 85% yield. Furthermore, high‐energy polymeric substances were derived by marrying the molecular intricacy between (E,E)‐1,4‐diiodobuta‐1,3‐diene and calcium carbide, underpinning a unique C4+C2 assembly blueprint. The structure and morphology of the polymeric material were characterized by IR and NMR spectroscopy, scanning electron microscopy, and energy dispersive X‐ray spectroscopy. Overall, two complementary 2×C2‐to‐C4 and (2×C2+C’2)×n assembly schemes were developed using Pt and Pd catalysis.

Carbon Monoxide as C1 Building Block in Fine Chemical Synthesis†

Comprehensive SummaryCarbon monoxide (CO) has become one of the most relevant and versatile renewable C1 building blocks for chemical synthesis, especially in the fine chemicals industry, due to the development of efficient and selective catalysts for its activation. In this review, we present a comprehensive critical analysis of the last 10 years literature on the use of CO as a renewable feedstock for fine chemicals production. The review is organized by type of catalytic reaction, namely alkene and alkyne carbonylation, hydroformylation, carbonylation of aryl halides, carbonylative cross‐coupling and C—H carbonylation. Notable examples of the synthesis of relevant building blocks and/or known pharmaceuticals are highlighted. Emphasis is placed on examples of utilizing CO as the C1 building block in one or more catalytic steps. The catalyst used and the reaction conditions are consistently presented throughout all of the examples.

Cobalt-Catalyzed Carbonylative Synthesis of 4-Oxobutanoates from Formamide and Ethylene.

The direct concurrent installation of amide and ester groups across olefin motifs represents a powerful and promising functionalization tool in organic chemistry. Herein, a ligand-free cobalt-catalyzed four-component radical relay carbonylative difunctionalization of ethylene for the synthesis of 4-oxobutanoates has been developed. Valuable C4 building blocks were produced in a highly atom-economical fashion.

Reductive N-Formylation of Nitroarenes Mediated by Rongalite.

Herein, we disclose a straightforward approach to access transition-metal-free reductive N-formylation of nitroarenes. This reaction integrates the dual role of rongalite, which acts as a reductant and a C1 building block concurrently. This provides an alternative method for the synthesis of N-aryl formamides from nitroarenes, including the construction of a C-N bond. The utility of this protocol was demonstrated by scale-up synthesis and late-stage functionalizations of complex molecules.

Palladium-Catalyzed Carbonylative Homocoupling of 2-Iodophenols for the Synthesis of Symmetrical Xanthones

AbstractHerein, we report the palladium-catalyzed carbonylative synthesis of symmetrical xanthones from functionalized 2-iodophenols in a one-pot manner. The protocol involves homocoupling of 2-iodophenols using Pd catalyst, Cs2CO3 as base, with gaseous CO as C1 building block. The simple, ligand- and additive-free strategy provides moderate to good yields of symmetrical xanthones. The reaction was also examined with the combination of 2-hydroxyphenyl boronic acid as another coupling partner. Additionally, this protocol was extended for the synthesis of aryl and alkyl salicylate derivatives by varying the reaction conditions.

Multicomponent Reactions for Expeditious Construction of β-Indole Carboxamide Amino Amides.

A multicomponent reaction of N-indole carboxylic acids, aldehydes, amines, and C2 building blocks can be transformed to structurally diverse β-indole carboxamide amino amides. In this multicomponent reaction, the ynamides and triazenyl alkynes act as the C2 building block, and this protocol features readily available starting materials, high atom economy, and mild reaction conditions. Besides, the acyl triazene group in the product can be easily transformed to differential groups to expand the structural diversity.

Tetraazacoronenes and Their Dimers, Trimers and Tetramers.

Tetraazacoronenes were synthesized from bay-functionalized tetraazaperylenes by Zr-mediated cyclization and four-fold Suzuki-Miyaura cross coupling. In the Zr-mediated approach, an η4 -cyclobutadiene-zirconium(IV) complex was isolated as an intermediate to cyclobutene-annulated derivatives. Using bis(pinacolatoboryl)vinyltrimethylsilane as a C2 building block gave the tetraazacoronene target compound along with the condensed azacoronene dimer as well as higher oligomers. The series of extended azacoronenes show highly resolved UV/Vis absorption bands with increased extinction coefficients for the extended aromatic cores and fluorescence quantum yields of up to 80 % at 659 nm.

1,3-Butadiynamides the Ethynylogous Ynamides: Synthesis, Properties and Applications in Heterocyclic Chemistry.

1,3-butadiynamides-the ethynylogous variants of ynamides-receive considerable attention as precursors of complex molecular scaffolds for organic and heterocyclic chemistry. The synthetic potential of these C4-building blocks reveals itself in sophisticated transition-metal catalyzed annulation reactions and in metal-free or silver-mediated HDDA (Hexa-dehydro-Diels-Alder) cycloadditions. 1,3-Butadiynamides also gain significance as optoelectronic materials and in less explored views on their unique helical twisted frontier molecular orbitals (Hel-FMOs). The present account summarizes different methodologies for the synthesis of 1,3-butadiynamides followed by the description of their molecular structure and electronic properties. Finally, the surprisingly rich chemistry of 1,3-butadiynamides as versatile C4-building blocks in heterocyclic chemistry is reviewed by compiling their exciting reactivity, specificity and opportunities for organic synthesis. Besides chemical transformations and use in synthesis, a focus is set on the mechanistic understanding of the chemistry of 1,3-butadiynamides-suggesting that 1,3-butadiynamides are not just simple alkynes. These ethynylogous variants of ynamides have their own molecular character and chemical reactivity and reflect a new class of remarkably useful compounds.

One-pot synthesis of fuel precursor from acetoin fermentation broth using ionic liquid-based salting-out extraction system

BackgroundThe development of biofuels, especially liquid hydrocarbon fuels, has been widely concerned due to the depletion of fossil resources. In order to obtain fuel precursors, the reaction of C–C bond formation is usually carried out with biomass derived ketones/aldehydes as reactants. Acetoin and 2,3-butanediol are two platform chemicals, which are co-existed in fermentation broth and traditionally separated by distillation, and then acetoin could be use as C4 building block to prepare hydrocarbon fuels. In order to mitigate the process complexity, direct aldol condensation reaction of acetoin in fermentation broth was studied in this work.ResultsA one-pot process of product separation and acetoin derivative synthesis was proposed based on salting-out extraction (SOE). Aldol condensation reaction of acetoin and 5-methyl furfural in different SOE systems was compared, and the results showed that the synthesis of C10 fuel precursors and separation of C10 products and 2,3-butanediol from fermentation broth were achieved in one-pot with ethanolammonium butyrate (EOAB) and K2HPO4 as SOE reagents and catalysts. The SOE and reaction conditions such as the concentrations of EOAB and K2HPO4, reaction temperature and time were optimized. When the system was composed of 6 wt% EOAB-44 wt% K2HPO4 and the mixture was stirred for 6 h at 200 rpm, 40 ℃, the yield of C10 products was 80.7%, and 95.5% 2,3-butanediol was distributed to the top EOAB-rich phase. The exploration of reaction mechanism showed that an imine intermediate was rapidly formed and the subsequent C10 product formation was the key step for aldol condensation reaction.ConclusionsWith EOAB and K2HPO4 as SOE reagents and catalysts, one-pot synthesis of fuel precursor from acetoin fermentation broth was achieved without prior purification. A yield of 80.7% for C10 products was obtained which was accumulated at the interface of two aqueous-phase, and 95.5% 2,3-BD was distributed to the top EOAB-rich phase. This work provides a new integration process of product separation and derivative synthesis from fermentation broth based on ionic liquid SOE.Graphical

Electrogenerated Sm(II)-Catalyzed Carbon Dioxide Reduction for β-Hydrocarboxylation of Styrenes

The synthesis of carboxylic acids from low-value materials such as alkenes using CO2 as a C1-building block remains a real challenge for synthetic chemists from both reactivity and selectivity perspectives. Electrochemical carboxylations have been examined but they remain limited, still suffering from a crucial lack of selectivity. Herein we report a catalytic protocol based on an electrogenerated Sm(II) catalyst as a powerful CO2 reductant, able to perform exclusively anti-Markovnikov hydrocarboxylation of alkenes. This electrochemical approach overcomes several current limitations and allows direct β-hydrocarboxylation of styrene derivatives, in a regioselective manner.

Salzabfall‐freie Carboxylierung von Acetylen: Grüne Synthese von C4‐Chemikalien durch einen CO2‐Druck‐induzierten Aciditätsswitch

AbstractDie Vermeidung der Bildung equimolarer Mengen an Salzabfällen ist eine der größten Herausforderungen zur Nutzung von CO2 als C1 Baustein in C‐H‐Carboxylierungsreaktionen. Zur Lösung dieses Problems wurde ein zyklischer Prozess entwickelt, in welchem die industrielle Basischemikalie Dimethylsuccinat aus CO2 und Acetylen synthetisiert wird. Bei moderatem CO2‐Druck kann Acetylen mit Cäsiumcarbonat zweifach carboxyliert und das intermediäre Salz durch Hydrierung der C‐C‐Dreifachbindung stabilisiert werden. Bei 70 bar CO2 wird das Reaktionsmedium reversibel angesäuert, was die Veresterung des Carboxylatsalzes mit dem Lösemittel Methanol ermöglicht. Die Cäsiumbase und der Hydrierkatalysator können regeneriert und wiederverwendet werden. Dieses Reaktionskonzept eröffnet einen neuen Weg zur Umsetzung von Biogas (CH4/CO2) zu industriell relevanten C4 Basischemikalien. Der reversible Aziditätsswitch, die Rolle der Cäsiumbase so wie die des Lösungsmittelgemisches wurden durch thermodynamische Modellierung aufgeklärt.

Carboxylation of Acetylene without Salt Waste: Green Synthesis of C4 Chemicals Enabled by a CO2-Pressure Induced Acidity Switch.

The inherent formation of salt waste in C-H carboxylations is a key obstacle precluding the utilization of CO2 as C1 building block in the industrial synthesis of base chemicals. This challenge is addressed in a circular process for the production of the C4 base chemical dimethyl succinate from CO2 and acetylene. At moderate CO2 pressures, acetylene is doubly carboxylated in the presence of cesium carbonate. Hydrogenation of the C-C triple bond stabilizes the product against decarboxylation. By increasing the CO2 pressure to 70 bar, the medium is reversibly acidified, allowing an esterification of the succinate salt with methanol. The cesium base and the hydrogenation catalyst are regenerated and can be reused. This provides the proof of concept for a salt-free route to C4 chemicals from biogas (CH4/CO2). The origin of this reversible acidity switch and the critical roles of the cesium base and the NMP/MeOH solvents were elucidated by thermodynamic modeling.

Modern Strategies for Carbon Isotope Exchange.

In contrast to stable and natural abundant carbon-12, the synthesis of organic molecules with carbon (radio)isotopes must be conceived and optimized in order to navigate through the hurdles of radiochemical requirements, such as high costs of the starting materials, harsh conditions and radioactive waste generation. In addition, it must initiate from the small cohort of available C-labeled building blocks. For long time, multi-step approaches have represented the sole available patterns. On the other side, the development of chemical reactions based on the reversible cleavage of C-C bonds might offer new opportunities and reshape retrosynthetic analysis in radiosynthesis. This review aims to provide a short survey on the recently emerged carbon isotope exchange (CIE) technologies that provide effective opportunity for late-stage labeling. At present, such strategies have relied on the use of primary and easily accessible radiolabeled C1-building blocks, such as carbon dioxide, carbon monoxide and cyanides, while the activation principles have been based on thermal, photocatalytic, metal-catalyzed and biocatalytic processes.

Mass Transport of Diazomethane across Teflon AF2400 Membrane for Scale-Up Development

Diazomethane is an attractive C1 building block in organic chemistry, but its hazardous nature presents scale-up challenges to this date. The use of a Teflon AF2400 membrane, most commonly in a tube-in-tube reactor setup, is the current state-of-the-art methodology for inherently safer laboratory-scale generation, separation, and consumption of anhydrous diazomethane. For the successful scale-up of this membrane process, the key mass transfer coefficient of the AF2400 membrane, its permeability for diazomethane, was investigated. We report in this contribution a novel methodology to determine diazomethane permeability for the rational scale-up of membrane processes for the safe handling of diazomethane. Missing physical properties of diazomethane were established, and the full mass balance of in situ-generated diazomethane within the tube-in-tube reactor was experimentally validated. A numerical model of the membrane reactor system in combination with experimental data yielded a permeability value of 414 barrer. This result enables scale-up development of the laboratory membrane reactor toward production-scale systems.

Recent Advances in the Electrocarboxylation of CO2 with Ketones, Aldehydes, and Imines

Abstract: Carbon dioxide (CO2) is regarded as an ideal C1 building block for the synthesis of value-added chemicals due to its low price, non-toxic, rich reserves, and recyclability. Organic electrosynthesis, using electricity as the driving force to avoid the use of toxic or expensive reducing agents, has become an efficient and environmentally friendly synthetic method and is widely used in the chemical conversion of CO2. In particular, the electrocarboxylation reaction of CO2 with a substrate containing a specific group, such as C=O and C=N, can be realized to synthesize α-hydroxy acids, amino acids, and their derivatives under mild reaction conditions by accurately adjusting the current or potential. In this review, we focus on the recent advances in the electrocarboxylation of CO2 with unsaturated substrates (including ketones, aldehydes, and imines) in the past five years, which we hope could stimulate further research on electrocarboxylation of CO2 with ketones, aldehydes, and imines and provide a reference for the application of such reactions in green organic electrosynthesis in the future.

Transition Metal‐Free Activation of Carbon Monoxide: Ketenyl Anions by PPh3/CO Exchange

AbstractKetenes (R2C=C=O) are important reactive intermediates in organic chemistry which are often challenging to access in stable form due to their polarized cumulenic structure and inherent high reactivity. Ketenyl anions (R(M)C=C=O) or metal ynolates (R−C≡C−OM) represent alternative, highly attractive synthetic targets, but are typically prepared in situ and their structure and synthetic access are little investigated. Now, a fundamentally new strategy utilizing an exchange reaction of a phosphine with carbon monoxide at a metalated ylide gives rise to a series of novel ketenyl anions. These compounds are flexible reagents and can easily be transferred with electrophiles into more complex building blocks for synthetic applications. Since carbon monoxide is an inexpensive C1 building block, the new exchange strategy is an elegant concept and a valuable new entry in the synthetic toolbox of organic synthesis.

Transition Metal-Free Activation of Carbon Monoxide: Ketenyl Anions by PPh3/CO Exchange.

This article highlights the recent findings reported by Gessner and co-workers in the synthesis of valuable ketenyl anions by an exchange of triphenylphosphine with carbon monoxide at a metaled ylide. The metal ketenyl/ynolate was structurally characterized and used as a reagent in organic synthesis.

Unveiling the theoretical aspects of superelectrophilic activation in an inverse demand Diels-Alder reaction.

The present computational study using B3LYP functional and 6-31+G(d) basis set has been accomplished to investigate the mechanism of the inverse demand Diels-Alder reaction between pyridyl imine and propene. The highly charged dicationic superelectrophilic diene with exceptionally low-lying LUMO makes the cycloaddition reaction with propene more favorable by significantly lowering the activation energy. The Wiberg bond indices are calculated in accordance with the formation and breaking processes of bonds. The synchronicity concept is also utilized to explain the global nature of the reaction. A potential outcome of this investigation is the utilization of propene as a C2 building block in the industry.