Robby Vroemans

The copper-catalyzed reaction between azides and alkynes, known as CuAAC, has allowed for the efficient synthesis of 1,2,3-trisubstituted 1,4-triazoles and the formation of a metallocycle intermediate. This intermediate can be used for creating new structures or generating multi-component reactions, collectively referred to as “interrupted click reactions”

Abstract

The particular and unique mechanism of the copper-catalyzed reaction between azides and alkynes (CuAAC) has not only allowed for the efficient synthesis of 1,2,3-trisubstituted 1,4-triazoles in excellent yields and under mild conditions, becoming the quintessential click reaction, but it has also enabled the straightforward formation of a metallocycle intermediate, the copper triazolyl. This, under suitable reaction conditions able to suppress its protonolysis, can be used either for the creation of new bicyclic triazolyl structures or for the generation of novel three or four-component reactions. The aim of this review is to rationalize and unify all these transformations, which are collectively referred to as “interrupted click reactions”.

Boryl-group-assisted reductive C−C bond cleavage of 1,2-diaryl-1,2-diborylethanes is described. The substrates, 1,2-diaryl-1,2-diborylethanes, are synthesized by reductive diboration of stilbenes. The combination of these reactions, reductive diboration and reductive cleavage provides a new strategy for reductive C=C double bond cleavage.

Abstract

In contrast to the well-established oxidative C=C double bond cleavage to give the corresponding carbonyl compounds, little is known about reductive C=C double bond cleavage. Here we report that C−C single bond cleavage in 1,2-diaryl-1,2-diborylethanes proceeds by reduction with sodium metal to yield α-boryl benzylsodium species. In combination with our previous reductive diboration of stilbenes, the overall transformation represents reductive cleavage of the C=C double bonds of stilbene to yield α-boryl-α-sodiated toluenes. This reductive two-step C=C double bond cleavage is applicable to ring-opening or ring-expansion reactions of polycyclic aromatic hydrocarbons.

Synthesis
DOI: 10.1055/a-2260-0346

A transition-metal-free synthesis of thiosulfonates has been accomplished by the disproportionate coupling of readily available and inexpensive sulfonyl hydrazides embracing hypervalent iodine(III) [phenyliodine(III) diacetate (PIDA)] as an oxidant. This synthesis involves cleavage of the S–N bond and is endowed with creation of a new S–S bond. The thiosulfonates were further reduced with CS2/KOH to obtain symmetrical disulfides. This protocol features mild reaction conditions in open air, an inexpensive oxidant, and high functional group tolerance with good to excellent product yields.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
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To address the growing demand for more sustainable and greener chemistry, mechanochemical methodologies are emerging as key players. Herein, we report the first application of bead-mill technology for the synthesis of Paracetamol. The proposed mechanochemical Paracetamol process achieves a higher yield and scores the highest for all the metrics while also allowing the removal of solvents, hereby significantly reducing the waste generation.

Abstract

To address the growing demand for more sustainable and greener chemistry, mechanochemical methodologies are emerging as key players. However, to date there has been little data highlighting the benefits of these rising mechanochemical technologies with regard to process scale-up activities or implementation in commercial production scale. Herein, we report the first application of bead-mill technology (Dyno®-mill) for the sustainable mechanochemical synthesis of Acetaminophen, known under the brand name Paracetamol. Using the Beckmann rearrangement, the optimized solvent-free methodology delivered a final product on a scale of several tens of grams. In comparison to current production solvent-based process, the proposed process achieves a higher yield while also allowing the removal of solvents in the chemical reaction, hereby reducing one of the extensive drivers to waste generation. The mechanochemical approach was compared to solvent-based process using a combination of green metrics and EcoScale score. The mechanochemical synthesis of paracetamol scores the highest for all the metrics over currently used solution-based processes.

The Front Cover depicts in an artistic manner the structure of a heterogeneous catalyst specifically tailored for Ullmann C−O type cross-couplings. In this material, the functionalization of graphite nanoplatelets with a polyaminic linker allowed the stabilization of Cu single atoms. The designed catalyst showed excellent activity, selectivity, recyclability, and flexibility toward various substrates in Ullmann-based C−O type transformations. More information can be found in the Research Article by G. Vilé and co-workers.

Publication date: January–February 2024

Source: Mendeleev Communications, Volume 34, Issue 1

Author(s): Agnieszka Mikus

Publication date: January–February 2024

Source: Mendeleev Communications, Volume 34, Issue 1

Author(s): Irina P. Blinova, Victor I. Deineka, Tatiana E. Nuzhnykh

Synthesis
DOI: 10.1055/a-2241-3571

The atroposelective transformation of alkynes is an efficient protocol for the assembly of axially chiral compounds. Benefitting from the rapid development of chiral organocatalysts, the organocatalytic atroposelective reactions of alkynes have been extensively studied over the past decades. An array of chiral catalysts, including chiral Brønsted acid catalysts, secondary amine catalysts, N-heterocyclic carbene (NHC) catalysts, thiourea catalysts and N-squaramide catalysts, are employed in enantioselective reactions of different alkynes. This short review summarizes the recent advances on organocatalytic atroposelective reactions of alkynes according to the type of alkyne substrate. The reaction mechanisms, modes of enantiocontrol, product diversity and applications are highlighted.1 Introduction2 Electron-Rich Aryl Alkynes3 Electron-Deficient Aryl Alkynes4 Other Types of Alkynes5 Conclusion and Outlook
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
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Nature, Published online: 06 February 2024; doi:10.1038/d41586-024-00347-7

Synlett
DOI: 10.1055/s-0042-1751549

The present article provides an overview of our work related to cyclization reactions of nitro-substituted electrophilic building blocks with various nucleophiles. As electrophiles, we used nitro-substituted benzoylacetones, 3-ethoxy-2-nitro-2-en-1-ones, 2-nitrobenzoyl chlorides, 4-chloro-3-nitrocoumarin, 2-nitromalonic aldehyde, 3-nitrochromone and 1-(2-chloro-5-nitrophenyl)prop-2-yn-1-ones. As nucleophiles, 1,3-dicarbonyl compounds, 1,3-bis(silyloxy)-1,3-butadienes, (heterocyclic) enamines, hydroxylamine, hydrazines, amines and amino esters were employed. The products include a variety of nitro-substituted carbo- and heterocycles that are not readily available by other methods. The electron-withdrawing nitro group can be easily transformed into an electron-donating amino group which is not only pharmacologically relevant, but can also act as a nucleophile in inter- and intramolecular reactions with electrophiles, such as aldehydes, and can be converted into other functional groups. The nitro group has the capacity to activate compounds for regioselective palladium-catalyzed CH-arylation reactions. Inter- and intramolecular CH arylations of nitro-substituted heterocyclic building blocks, such as 4-nitropyrazoles, 4-nitroimidazoles, 2-nitroindole and nitro-substituted purine analogues, allow for a convenient diversity-oriented approach to the corresponding arylated products. In addition, the nitro group can act as a leaving group in SNAr reactions. Various fused benzofuro[3,2-b]pyridines were prepared by intramolecular SNAr reactions of 2-(hydroxyphenyl)-3-nitropyridines.1 Introduction2 Cyclizations of 1,3-Bis(silyloxy)-1,3-butadienes3 Cyclizations of Heterocyclic Enamines4 Reactions of Simple Nitro-Substituted Heterocycles5 Hydroamination Reactions of Alkynes6 Miscellaneous7 Conclusions
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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This review explores the innovative realm of interfacial photoelectrochemical (iPEC) and photoelectrochemical (PEC) catalysis, seamlessly integrating electrochemical and photoredox processes for efficient reactions. Utilizing minimal photocatalysts, visible light catalyzes a range of reactions through single-electron events. Despite its early stage, this synergistic approach holds promise for advancing organic synthesis, with potential applications in late-stage modifications, and bioconjugation strategies for biomolecule modifications.

Abstract

This review delves into the innovative field of interfacial photoelectrochemical (iPEC) and photoelectrochemical (PEC) catalysis, the dynamic synthesis methodologies that seamlessly integrates electrochemical and photoredox catalysis for efficient and environmentally friendly reactions. Utilizing minute quantities of photocatalysts, visible light becomes a powerful tool, generating transient excited states to catalyze a spectrum of reactions through single-electron oxidation or reduction events. The review categorizes recent advancements, highlighting applications in organic synthesis, late-stage modifications, and the distinctive features of photoelectrochemical methodology. Despite being in its early stages, this synergistic approach holds great promise for propelling organic synthesis forward, with potential applications in large-scale synthesis and diverse late-stage functionalizations, including asymmetric catalysis and bioconjugation strategies for biomolecule modifications.

The hydrogen-transfer strategy is pivotal in realizing sustainable and eco-friendly lignin refinement. This concept review concentrates on the attributes of multifunctional hydrogen donors and their utilization in the upgrading of lignin-derived materials. The paper explores both the present challenges and the prospective avenues for advancing the hydrogen-transfer strategy within the realm of lignin refinement.

Abstract

Lignin, the most prevalent natural source of polyphenols on Earth, offers substantial possibilities for the conversion into aromatic compounds, which is critical for attaining sustainability and carbon neutrality. The hydrogen-transfer method has garnered significant interest owing to its environmental compatibility and economic viability. The efficacy of this approach is contingent upon the careful selection of catalytic and hydrogen-donating systems that decisively affect the yield and selectivity of the monomeric products resulting from lignin degradation. This paper highlights the hydrogen-transfer technique in lignin refinery, with a specific focus on the influence of hydrogen donors on the depolymerization pathways of lignin. It delineates the correlation between the structure and activity of catalytic hydrogen-transfer arrangements and the gamut of lignin-derived biochemicals, utilizing data from lignin model compounds, separated lignin, and lignocellulosic biomass. Additionally, the paper delves into the advantages and future directions of employing the hydrogen-transfer approach for lignin conversion. In essence, this concept investigation illuminates the efficacy of the hydrogen-transfer paradigm in lignin valorization, offering key insights and strategic directives to maximize lignin's value sustainably.

The features of a category of reversible nucleophilic aromatic substitution reactions in view of their significance and wide scope in aromatic and heteroaromatic chemistry are presented. Exchange of sulfur components surrounding arenes and heteroarenes may occur at 25 °C, in a process that one may call a “sulfur dance”. A dynamic covalent system involving four components illustrates the thermodynamically-driven formation of a thiacalix[2]arene[2]pyrimidine. This work stimulates the implementation of reversible S_NAr reactions in organic, materials and covalent dynamic chemistry.

Abstract

We disclose the features of a category of reversible nucleophilic aromatic substitutions in view of their significance and generality in dynamic aromatic chemistry. Exchange of sulfur components surrounding arenes and heteroarenes may occur at 25 °C, in a process that one may call a “sulfur dance”. These S_NAr systems present their own features, apart from common reversible reactions utilized in dynamic covalent chemistry (DCC). By varying conditions, covalent dynamics may operate to provide libraries of thiaarenes with some selectivity, or conversion of a hexa(thio)benzene asterisk into another one. The reversible nature of S_NAr is confirmed by three methods: a convergence of the products distribution in reversible S_NAr systems, a related product redistribution between two per(thio)benzenes by using a thiolate promoter, and from kinetic/thermodynamic data. A four-component dynamic covalent system further illustrates the thermodynamically-driven formation of a thiacalix[2]arene[2]pyrimidine by sulfur component exchanges. This work stimulates the implementation of reversible S_NAr in aromatic chemistry and in DCC.

Triflate's bigger brother: The unprecedented tribrate anion [Br₃CSO₃]^– is flanked by its smaller siblings, the triflate and the trichlate anions. The new big brother was obtained by bromination of phenyl methane sulfonate with KOBr, followed by splitting of the ester under basic conditions. The new anion was studied through X-ray diffraction of its potassium salt. Furthermore, the thermal decomposition was investigated, and the Raman data of the anion are reported. The background image shows the church tower of the famous cathedral of Cologne, the place of birth for the new anion. More information can be found in the Research Article by M. S. Wickleder and co-workers (DOI: 10.1002/chem.202303617).

Abstract

Mn(II)-catalyzed alkylations of methyl N-heteroarenes was reported via borrowing hydrogen strategy with alcohols as the alkylating reagent. The developed geometry-constrained benzimidazole-iminopyridyl ligand played a key role in promoting the transformation and stablizing the metal center. A wide range of alcohols (aromatic, heteroaromatic and aliphatic) and methyl N-Heteroarenes could be able to apply in the current catalytic system, with TON up to 7400.