Mathias

The visible-light and chiral-Lewis-acid synergistically catalyzed reductant-free asymmetric aza-Reformatsky reaction is described by Xiaoming Feng and co-workers in their Communication (e202500756). Control experiments revealed a direct SET process between excited state imine and α-iodo difluoromethyl carbonyl compound which prevents the use of reductant.

Nature Chemistry, Published online: 20 January 2025; doi:10.1038/s41557-024-01728-1

Nature Catalysis, Published online: 09 January 2025; doi:10.1038/s41929-024-01282-6

Synthesis
DOI: 10.1055/s-0043-1775416

Anilines are a common motif in many bioactive compounds and their production through the reduction of nitroarenes has become an essential method for their synthesis. We demonstrate that the combination of an amine-borane complex and hypoboric acid (tetrahydroxydiborane) under visible light irradiation can accomplish the reduction of nitroarenes to the corresponding anilines. Preliminary mechanistic studies suggest the generation of boryl radicals via a hydrogen atom transfer (HAT) step from the photoexcited nitroarene. Involvement of a parallel thermal pathway is demonstrated with the high reaction efficiency being partially attributed to both routes.
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Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

A photoinduced Bartoli indole synthesis was first reported for the construction of indoles and azaindoles by the oxidative cleavage of alkenes with nitro(hetero)arenes. The novel reactivity of N−O=C dipoles, involving the rearrangement of carbonyl imines, enhances the comprehension of dipole chemistry.

Abstract

Given the unique charm of dipole chemistry, intercepting N−O=C dipoles precisely generated by designed processes to develop novel reactivity has become a seminal challenge. The polar fragmentation of 1,3,2-dioxazolidine species generated through the radical addition of excited nitro(hetero)arenes to alkenes represents a significantly underappreciated mechanism for generating N−O=C dipoles. Herein, we present a photoinduced Bartoli indole synthesis by the oxidative cleavage of alkenes with nitro(hetero)arenes. Various indoles and azaindoles are constructed through the multi-step spontaneous rearrangement of carbonyl imine intermediates generated by the polar fragmentation of 1,3,2-dioxazolidine species. Mechanism studies and DFT calculations support that the reaction involves radical cycloaddition, ozonolysis-type cycloreversion, intramolecular H-shift of carbonyl imines, and 3,3-sigmatropic shift of O-Alkenyl hydroxylamines, etc. The implementation of continuous- flow photochemistry, in particular, significantly enhances efficiency, thereby overcoming obstacles to the commercialization process.

Abstract

The ever-increasing prevalence of diseases and inadequate resources on Earth are threats to society. Biomass is an abundant resource, and bioactive compounds produced from biomass are environmentally benign in contrast to conventional chemical synthesis methods, which frequently depend on non-renewable resources. In addition, the functionalized monomers from biomass allow the atom economical synthesis of bioactive molecules. This review aims to provide insight into the synthesis of bioactive molecules from the lignocellulose-derived platform chemicals. Existing methodology and catalytic systems are summarized for the synthesis of targeted bioactive molecules from cellulose, hemicellulose, and lignin-derived platform chemicals. The biological activities of bioactive molecules obtained from biomass, such as antioxidant, anti-inflammatory, and anticancer properties, are discussed.

This study presents a copper-catalyzed, solvent-dependent route for the rapid and efficient synthesis of N-pyrazolo-sulfonamides directly from nitro-pyrazole and sulfonyl hydrazide under microwave conditions. Solvent dependent reactivity and remarkable chemoslectivity are some of the key features of this method. Further utility of the process is demonstrated by the sulfaphenazole analogue and sulfonamide nucleoside synthesis.

Abstract

This study presents a copper-catalyzed, solvent-dependent method for the rapid and efficient synthesis of N-pyrazolo-sulfonamides directly from nitro-pyrazole and sulfonyl hydrazide under microwave conditions. The reaction exhibits notable solvent effects in pyrazole's reactivity. The ionic liquid DBU-AcOH triggered the reactivity of 4-nitro-pyrazole, whereas the reaction in PEG proceeded selectively at the 3- & 5-positions of pyrazole. Key applications of this method include the gram-scale synthesis of pyrazolo-sulfonamide, sulfaphenazole analogue and sulfonamide nucleoside.

A visible-light-promoted reduction of nitrobenzenes using the formate salt as the reductant is developed. A range of nitrobenzenes can be converted into value-added anilines under blue light irradiation. Mechanistic studies revealed that arene thiol radicals and CO₂⋅⁻ are key intermediates for the transformation. The protocol represents a transition metal free and green example for the realization of such transformations.

Abstract

A visible-light-promoted reduction of nitrobenzenes using formate salts as the reductant was developed. A wide range of nitrobenzenes can be converted into aniline products in a transition metal free fashion. Mechanistic studies revealed that radical species (carbon dioxide radical anion and thiol radical) are key intermediates for the transformation. We anticipate that this method will provide a valuable and green strategy for the reduction of nitrobenzenes.

Publication date: 7 November 2024

Source: Tetrahedron, Volume 167

Author(s): Piao Ding, Eman Fayad, Ola A. Abu Ali, Hua-Li Qin

Abstract

Flavin-dependent nitroreductases are gaining attention as biocatalysts for the synthesis of pharmaceutically active compounds and their precursors. Here, we examined a panel of nitroreductase-like flavoenzymes for their reductase activity towards a wide variety of aromatic and aliphatic nitro compounds, nitroolefins, and α,β-unsaturated carbonyl compounds. Several of these flavoenzymes displayed high reductase activity and achieved excellent conversion of diverse nitroarenes, nitroolefins and α,β-unsaturated carbonyl compounds, accomplishing good product yields in semi-preparative scale reactions (up to 97%). In addition to the catalytic promiscuity of several of these flavoenzymes, being able to perform the reduction of nitro groups (nitroreductase activity) as well as C=C groups (ene-reductase activity), this study also revealed that some flavoenzymes exhibit high chemo-, regio- and/or enantioselectivity, making them attractive enzymes for use in organic synthesis.

Nitroarenes can be readily synthesized from arenes through direct nitration, and their functionalization via C−NO₂ bond cleavage offers a rapid approach for the modification of arenes. The method not only streamlines the synthetic routes but also minimizes waste generation, enabling the construction of C−C, C−N, C−Si, C−B, C−S, C−O, C−Se, and C−H bonds. In this review, we provide an overview of recent advancements in this field.

Abstract

Nitroarenes are fundamental feedstocks in the chemical industry. Their relatively inert C−NO₂ bond allows for late-stage modifications of molecules and exhibits complete orthogonality to the reactivity of C-halogen bond in cross-coupling reactions. The denitrative functionalization of nitroarenes holds significant appeal due to it avoids the use of aryl halides, thereby simplifying reaction steps and improving atom and step economy. Recent progress in direct denitrative functionalization of nitroarenes includes palladium-catalyzed denitrative coupling, copper-catalyzed denitrative coupling, as well as metal-free one-pot C−NO₂ functionalization. In this review, we provide a concise overview of these advancements, detailing the reaction features and mechanisms. This summary aims to highlight the versatility and efficiency of denitrative functionalization methodologies, offering insights into their potential applications and inspiring further research in this promising area of organic synthesis.

Synthesis
DOI: 10.1055/s-0043-1775032

This study aims to delineate the synthesis of eugenol derivatives, starting with hydroxyl group protection and then the subsequent oxidation stages. Initially, eugenol underwent conversion into acetyleugenol and benzyleugenol during the protection phase. Subsequently, a kinetic oxidation of acetyleugenol with KMnO4 via GC-MS analysis resulted in the identification of four compounds. The kinetic investigation indicated the primary formation of diolacetyleugenol, succeeded by aldehyde eugenol, which further gets converted into its respective carboxylic acid. Additionally, acetyleugenol and benzyleugenol underwent oxidation with CrO3, yielding the corresponding carboxylic acids.
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Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

An atom-efficient domino strategy maximizing the yield of non-phenolic dealkylated aromatics from the lignin β-O-4 motif by one-pot catalytic cascade, consisting of selective dehydrogenation of γ-carbinol group, retro-aldol to cleave C−C bonds, and decarbonylation of the generated aldehydes.

Abstract

Aromatic monomers obtained by selective depolymerization of the lignin β-O-4 motif are typically phenolic and contain (oxygenated) alkyl substitutions. This work reveals the potential of a one-pot catalytic lignin β-O-4 depolymerization cascade strategy that yields a uniform set of methoxylated aromatics without alkyl side-chains. This cascade consists of the selective acceptorless dehydrogenation of the γ-hydroxy group, a subsequent retro-aldol reaction that cleaves the C_α−C_β bond, followed by in situ acceptorless decarbonylation of the formed aldehydes. This three-step cascade reaction, catalyzed by an iridium(I)-BINAP complex, resulted in 75 % selectivity for 1,2-dimethoxybenzene from G-type lignin dimers, alongside syngas (CO : H₂≈1.4 : 1). Applying this method to a synthetic G-type polymer, 11 wt % 1,2-dimethoxybenzene was obtained. This versatile compound can be easily transformed into 3,4-dimethoxyphenol, a valuable precursor for pharmaceutical synthesis, through an enzymatic catalytic approach. Moreover, the hydrodeoxygenation potential of 1,2-dimethoxybenzene offers a pathway to produce valuable cyclohexane or benzene derivatives, presenting enticing opportunities for sustainable chemical transformations without the necessity for phenolic mixture upgrading via dealkylation.

We hereby introduce a potent and modular synthetic strategy for the assembly of valuable acridine architectures, leveraging the synergistic combination of photo-excitation of o-alkyl nitroarenes with copper-mediated cascade annulation. This approach facilitates the rapid construction of a diverse collection of symmetric, unsymmetric, and poly-substituted acridines, which can be seamlessly converted into precious acridinium photocatalysts. Notably, certain members of this class exhibit extraordinary oxidative strength, thereby unlocking immense potential for advancing the realm of photochemical reactions.

Abstract

Acridine frameworks stand as pivotal architectural elements in pharmaceuticals and photocatalytic applications, owing to their chemical adaptability, biological activity, and unique excited-state dynamics. Conventional synthetic routes often entail specialized starting materials, anaerobic or moisture-free conditions, and elaborate multi-stage manipulations for incorporating diverse functionalities. Herein, we present a convergent approach integrating photo-excitation of readily available ortho-alkyl nitroarenes with copper-promoted cascade annulation. This innovative system enables an aerobic, one-pot reaction of o-alkyl nitroarenes with arylboronic acids, thereby streamlining the modular construction of a wide array of acridine derivatives with various functional groups. This encompasses symmetrical, unsymmetrical and polysubstituted varieties, some of which are otherwise exceptionally difficult to synthesize. Furthermore, it significantly improves the production of structurally varied acridinium salts, featuring enhanced photophysical properties, high excited state potentials (E*_red=2.08–3.15 V), and exhibiting superior performance in intricate photoredox transformations.

Bis(NHC)Mn(I) catalysed effective transfer hydrogenation of epoxides, azoarenes and nitroarenes to alcohols, hydrazoarenes and anilines respectively under mild conditions using ammonia borane is demonstrated. A series of mechanistic investigations were carried out to understand the catalytic process.

Abstract

Herein, we have reported an effective protocol for the regioselective transfer hydrogenation (TH) of epoxides by utilizing a phosphine-free bis-NHC−Mn(I) complex and ammonia borane. By employing this strategy, aromatic epoxides were selectively converted to primary alcohols whereas secondary alcohols were obtained exclusively from aliphatic epoxides. The protocol was further extended for the TH of azoarenes and nitroarenes to hydrazoarenes and anilines respectively. Notably, a library of substrates with different functional groups were screened which resulted in the corresponding transfer hydrogenated product in good to excellent yields. A series of mechanistic investigations were carried out to understand the catalytic process.