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The one-pot four-component condensation of benzoic acid (R1), aniline (R2), benzaldehyde (R3), and 2-isocyano-2-methylpropane was investigated at the B3LYP/6-311G** level to explore the reaction mechanism as a theoretical study. All routes were studied and structure of intermediates (IM) was optimized and all of the respective transition states (TS) were found. The calculation results proved that the proposed mechanism consists of eight steps that rate determining the state is nucleophilic attack of isocyanide to benzaldehyde. [ABSTRACT FROM AUTHOR]

We have demonstrated a unique reductive coupling of 4‐iodophenyl isocyanide, facilitated by a perimidine‐based N‐heterocyclic germylene (NHGe), which yields a bis‐spirogerma compound featuring simultaneous C−C and C−N bond formation. This reaction, which leads to the oxidation of germanium from +2 to +4, represents a significant departure from previously documented isocyanide‐germylene interactions. The product exhibits extensive conjugation across its bicyclic C4Ge2N2 framework, conferring distinct photophysical properties, including prominent orange luminescence in both solution and solid states. The photophysical properties are supported by the TD‐DFT calculations confirming an n→π* transition. The potential application of this compound in optoelectronic devices, particularly as a hole transport layer in PbS quantum dot solar cells, is also explored, with promising preliminary results. [ABSTRACT FROM AUTHOR]

Metal–organic frameworks (MOFs) have been widely studied due to their versatile applications and easily tunable structures. However, heteroatom‐metal coordination dominates the MOFs community, and the rational synthesis of carbon–metal coordination‐based MOFs remains a significant challenge. Herein, two‐dimensional (2D) MOFs based on silver–carbon linkages are synthesized through the coordination between silver(I) salt and isocyanide‐based monomers at ambient condition. The as‐synthesized 2D MOFs possess well‐defined crystalline structures and a staggered AB stacking mode. Most interestingly, these 2D MOFs, without π–π stacking between layers, exhibit narrow band gaps down to 1.42 eV. As electrochemical catalysts for converting CO2 to CO, such 2D MOFs demonstrate Faradaic efficiency over 92 %. Surprisingly, the CO2 reduction catalyzed by these MOFs indicates favorable adsorption of CO2 and *COOH on the active carbon sites of the isocyanide groups rather than on silver sites. This is attributed to the critical σ donor role of isocyanides and the corresponding ligand‐to‐metal charge–transfer effect. This work not only paves the way toward a new family of MOFs based on metal–isocyanide coordination but also offers a rare platform for understanding the electrocatalysis processes on strongly polarized carbon species. [ABSTRACT FROM AUTHOR]

Spiro-heterocyclic indolenines are privileged scaffolds widely present in numerous indole alkaloids. Here, we develop a novel approach for the one-pot multistep synthesis of different spiro[indole-isoquinolines]. The protocol proposed involves the visible light mediated oxidation of N-aryl tertiary amines using bromochloroform with the generation of a reactive iminium species, which reacts with an isocyanide and an electron-rich aniline in a three-component Ugi-type reaction to give an α-aminoamidine. This compound might undergo an additional visible light-mediated oxidation to furnish a second iminium intermediate, which acts as electrophile in an intramolecular electrophilic aromatic substitution giving the final spiro-indolenine. The scope of the process has been investigated with respect to all three components. Simple operations, mild conditions, and good yields make this strategy a convenient and sustainable way to obtain novel spiro-indolenine derivatives.

Isotopic labeling is an attractive modality that has been widely used in many aspects of chemistry, the life sciences, and medical research; especially deuterated drugs and radioactive molecules have been used in the diagnosis and treatment of cancer and neurodegenerative diseases. The widespread application and rapid development of isotopically labeled molecules has led to an increased demand for new isotopic labeling chemical methods to synthesize highly specific molecules bearing defined nuclides. Multicomponent reactions (MCRs) are modular build-up approaches for the rapid generation of complex molecules often containing biologically relevant scaffold structures. There is great potential to use MCRs to construct isotopically labeled molecules because assembly speed and reaction diversity are key advantages of MCR. In this review, we provide an overview of the recent literature on this topic that can provide insight into the application of MCRs in the field of isotopic labeling. [ABSTRACT FROM AUTHOR]

Isocyanide is a promising synthetic reagent not only as a one-carbon homologation reagent but also as a nitrogen source for nitrogen-containing molecules. Because of their isoelectronic structure with carbon monoxide, isocyanides also react with nucleophiles, electrophiles, carbon radicals, and transition metal reagents, and are widely used in organic synthesis. On the other hand, the use of isocyanides in reactions with heteroatom radicals is limited. However, the reaction of isocyanides with heteroatom radicals is a promising synthetic tool for the construction of nitrogen-containing organic molecules modified with a variety of heteroatoms. In this Perspective, we review the addition and cyclization reactions of heteroatom radicals with isocyanides and discuss the synthetic prospects of the reaction of isocyanides with heteroatom radicals.

An efficient protocol for the synthesis of polyfunctionalized tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine-3,4b,5,6,7(1H)-pentacarboxylates was developed by a three-component reaction. In the absence of any catalyst, the three-component reaction of alkyl isocyanides, dialkyl but-2-ynedioates and 5,6-unsubstituted 1,4-dihydropyridines in refluxing acetonitrile afforded polyfunctionalized tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine-3,4b,5,6,7(1H)-pentacarboxylates in high yields and with high diastereoselectivity. The reaction was finished by in situ generation of activated 5-(alkylimino)cyclopenta-1,3-dienes from addition of alkyl isocyanide to two molecules of but-2-ynedioates and sequential formal [3 + 2] cycloaddition reaction with 5,6-unsubstituted 1,4-dihydropyridine.

An efficient palladium‐catalyzed three‐component reaction for the synthesis of tricyclic fused 1,2,3‐triazole derivatives from amino‐NH‐1,2,3‐triazoles, isocyanide and iodoarenes has been developed, involving three new bonds formation by one manipulation in moderate to good yields with excellent functional group tolerance. Moreover, it is also suitable for other N‐heterocyclic substrates including pyrazole, imidazole, indole, tetrazole and its derivatives. [ABSTRACT FROM AUTHOR]

Using 1. 3-bis (2-iodoaryl) propane-2-amines as substrates, a palladium-catalyzed sequential insertion of isocyanide and carbon monoxide to construct isoquinolinone skeletons has been developed. Compared with isoelectronic isocyanide counterparts, the migratory insertion of isocyanide to Ar-Pd (II) is still prefer to carbon monoxide although carbon monoxide exists in large excess in the reaction. Followed by carbon monoxide insertion and finally reductive elimination, the corresponding isoquinolinone tetracyclic compounds were obtained. The reaction conditions were mild and the yields are up to 85%. The product was correctly identified by ¹ HNMR. 13C NMR and high-resolution mass spectrometry. [ABSTRACT FROM AUTHOR]

A novel single-step method has been developed for the synthesis of 1-(1-isocyanoethyl)adamantane from 1-(1-adamantylethyl)amine, chloroform, and t-BuOK, in a dichloromethane/tert-butanol (1:1) medium, yielding 92%, which is 27% higher compared to the known method, without the use of highly toxic compounds. The product was characterized using 1H and 13C NMR spectroscopy, GC-MS, and elemental analysis. [ABSTRACT FROM AUTHOR]

Smart solvatochromic isocyano-aminoarenes (ICAArs) have been gaining attention owing to their unique photophysical, antifungal and anticancer properties. Using a simple dehydration reaction with in situ-generated dichlorocarbene, we prepared 2-amino-7-isocyanofluorene (2,7-ICAF). We studied the effect of the longer polarization axis provided by the fluorene core on the spectral properties and we also compared it to those of the starting diamine. 2,7-ICAF shows a clear solvatochromic behavior close to the blue part (370–420 nm) of the visible spectrum. Quantum chemical calculations show internal charge transfer (ICT) between the donor amino and the electron-withdrawing isocyano groups. 2,7-ICAF has high molar absorptivity (ε = 15–18·103 M−1cm−1) and excellent quantum yield (Φf = 70–95%) in most solvents; however, its fluorescence is completely quenched in water. The high brightness (ε·Φf) and close to zero quantum yield in water may be favorable in biolabeling applications, where background fluorescence should be kept minimal. Overall, 2,7-ICAF shows enhanced photophysical properties compared to its previously investigated relative 4-amino-4′-isocyano-1,1′-biphenyl (4,4′-ICAB). [ABSTRACT FROM AUTHOR]

Smart solvatochromic isocyano-aminoarenes (ICAArs) have been gaining attention owing to their unique photophysical, antifungal and anticancer properties. Using a simple dehydration reaction with in situ-generated dichlorocarbene, we prepared 2-amino-7-isocyanofluorene (2,7-ICAF). We studied the effect of the longer polarization axis provided by the fluorene core on the spectral properties and we also compared it to those of the starting diamine. 2,7-ICAF shows a clear solvatochromic behavior close to the blue part (370–420 nm) of the visible spectrum. Quantum chemical calculations show internal charge transfer (ICT) between the donor amino and the electron-withdrawing isocyano groups. 2,7-ICAF has high molar absorptivity (ε = 15–18·103 M−1cm−1) and excellent quantum yield (Φf = 70–95%) in most solvents; however, its fluorescence is completely quenched in water. The high brightness (ε·Φf) and close to zero quantum yield in water may be favorable in biolabeling applications, where background fluorescence should be kept minimal. Overall, 2,7-ICAF shows enhanced photophysical properties compared to its previously investigated relative 4-amino-4′-isocyano-1,1′-biphenyl (4,4′-ICAB).

Ligand‐exchange reactions on a mangana(II)cyclopentasilane complex that contains two THF ligands with aryl isocyanides led to the formation of manganese(0) bis(η2‐disilene) complexes via a retrocyclization. In stark contrast, ligand‐exchange reactions with CNtBu, an N‐heterocyclic carbene, or pyridine‐based ligands furnished manganese(II) complexes wherein the manganacyclopentasilane framework remained intact. The thermolysis of the obtained bis(η2‐disilene) complex in the presence of mesityl isocyanide led to the formation of a cyclotetrasilane via the formal dimerization of the two η2‐disilene moieties. The insertion of a mesityl isocyanide into the Mn−Siβ bond results in the formation of a manganese(II) complex supported by a [SiCSi]‐type tridentate ligand scaffold. [ABSTRACT FROM AUTHOR]

A novel single-step method has been developed for the synthesis of 1-(1-isocyanoethyl)adamantane from 1-(1-adamantylethyl)amine, chloroform, and t-BuOK, in a dichloromethane/tert-butanol (1:1) medium, yielding 92%, which is 27% higher compared to the known method, without the use of highly toxic compounds. The product was characterized using 1H and 13C NMR spectroscopy, GC-MS, and elemental analysis.

Comprehensive Summary: A series of 3‐acyl‐substituted isoindolinone derivatives were synthesized in a one‐pot manner via the reaction of o‐bromobenzaldehydes, isocyanides, and carboxylic acids in the presence of palladium catalyst and base. The reaction employing easily available starting materials features simple operation and high efficiency. The mechanistic study showed that the reaction might undergo 1) Pd‐catalyzed [3+2] cyclization of o‐bromobenzaldehyde with isocyanide and the re‐insertion of another molecule of isocyanide, 2) addition of carboxylic acid to in situ formed ketenimine followed by a rearrangement relay to give 3,3‐diacyl‐substituted isoindolinone derivative. Further transformations of the obtained products through decarbonylation could also be realized. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: A series of 3‐acyl‐substituted isoindolinone derivatives were synthesized in a one‐pot manner via the reaction of o‐bromobenzaldehydes, isocyanides, and carboxylic acids in the presence of palladium catalyst and base. The reaction employing easily available starting materials features simple operation and high efficiency. The mechanistic study showed that the reaction might undergo 1) Pd‐catalyzed [3+2] cyclization of o‐bromobenzaldehyde with isocyanide and the re‐insertion of another molecule of isocyanide, 2) addition of carboxylic acid to in situ formed ketenimine followed by a rearrangement relay to give 3,3‐diacyl‐substituted isoindolinone derivative. Further transformations of the obtained products through decarbonylation could also be realized. [ABSTRACT FROM AUTHOR]

The established strategy unveils a metal and mediator‐free electrochemical [3+2] cycloaddition approach among α‐amino carbonyls and tosylmethyl isocyanide (TosMIC) fabricating substituted imidazole scaffolds. Implementation of electro‐redox conditions on this cycloaddition approach eliminates the essential requirement of transition metal catalysts and chemical oxidants. A wide variety of different functionalities are well tolerated under this reaction condition, contributing to the substrate scope and applicability. Several control experiments and cyclic voltammetry studies suggest an electro‐oxidation triggered successive C−C and C−N bond formations followed by rapid aromatization for constructing the five‐membered core structure. [ABSTRACT FROM AUTHOR]

Three series of palladium(II) complexes supported by a phosphine‐iminophosphorane ligand built upon an ortho‐phenylene core were investigated to study the influence of the iminophosphorane N substituent. Cis‐dichloride palladium(II) complexes 1 in which the N atom bears an isopropyl (iPr, 1 a), a phenyl (Ph, 1 b), a trimethylsilyl (TMS, 1 c) group or an H atom (1 d) were synthesized in high yield. They were characterized by NMR, IR spectroscopy, HR‐mass spectrometry, elemental analysis, and X‐ray diffraction. A substantial bond length difference between the Pd−Cl bonds was observed in 1. Complexes 1 a–d were converted into [Pd(LR)Cl(CNtBu)](OTf)] 2 a–d whose isocyanide is located trans to the iminophosphorane. The corresponding dicationic complexes [Pd(LR)(CNtBu)2](OTf)23 a–d were also synthesized, however they exhibited lower stability in solution than 2, the isopropyl derivative 3 a being the most stable of the series. Molecular modeling was performed to rationalize the regioselectivity of the substitution of the single chloride by isocyanide (from 1 to 2) and to study the electronic distribution in the complexes. In particular differences between the TMS and H containing complexes vs. the iPr and Ph ones were found. This suggests that the nature of the N substituent is far from innocent and can help tune the reactivity of iminophosphorane complexes. [ABSTRACT FROM AUTHOR]

To develop a novel 99mTc-labeled ubiquicidin 29-41 derivative for bacterial infection single-photon emission computed tomography (SPECT) imaging with improved target-to-nontarget ratio and lower nontarget organ uptake, a series of isocyanide ubiquicidin 29-41 derivatives (CNnUBI 29-41, n = 5–9) with different carbon linkers were designed, synthesized and radiolabeled with the [99mTc]Tc(I)+ core, [99mTc][Tc(I)(CO)3(H2O)3]+ core and [99mTc][Tc(V)N]2+ core. All the complexes are hydrophilic, maintain good stability and specifically bind Staphylococcus aureus in vitro. The biodistribution in mice with bacterial infection and sterile inflammation demonstrated that [99mTc]Tc-CN5UBI 29-41 was able to distinguish bacterial infection from sterile inflammation, which had an improved abscess uptake and a greater target-to-nontarget ratio. SPECT imaging study of [99mTc]Tc-CN5UBI 29-41 in bacterial infection mice showed that there was a clear accumulation in the infection site, suggesting that this radiotracer could be a potential radiotracer for bacterial infection imaging. [ABSTRACT FROM AUTHOR]

First-row transition metal catalyzed transformations that are able to construct complex molecules from simple, readily obtainable feedstocks have become a keystone of modern synthetic organic chemistry. Particularly, the multicomponent reaction (MCR) involving carbon–carbon (C–C) as well as carbon–heteroatom (C–X) bond formation plays an essential role in many chemical conversions, and insurgencies in these reactions powerfully improve the overall synthetic efficiency. Recently, MCRs emerges rapidly because of its greener sides like eco-friendly nature, swift and straightforward execution, high atom/step economy, and construction of aimed product with lowest or no by-product, usually in quantitative yield. Curiously, the exceptional divalent carbon atoms of isocyanides make them predominantly useful components in multicomponent reactions. As a result of widespread research over the past few decades, numerous well-designed and effective procedures for the first-row TM-catalyzed MCR to afford the various entities have been reported. These aspects are summarized in this review article. A particular focus on comparative discussion of various first-row transition-metal catalyzed isocyanide-based multicomponent reactions through mechanistic details included in the review article. [ABSTRACT FROM AUTHOR]

The protonation, or Lewis Acid complexation, of electrophiles can trigger the sequential insertion of two or more isocyanides resulting in valuable iminonitriles or heterocycles. The number of insertions is controlled by the nature of the alkyl- or arylisocyanide and by the presence of a proximal nucleophile capable of attacking the intermediate nitrilium; loss of an alkyl group from the nitrilium or attack by a nucleophile terminates further isocyanide insertions. The mechanistic survey of protic and Lewis acid-promoted isocyanide insertions aims to provide a fundamental understanding of the reactivity and selectivity to facilitate synthetic applications. The review is structured with an introductory overview followed by a mechanistic analysis before moving to a survey of double insertions, which are the most prevalent, then triple insertions; the survey concludes with the sole example of a quadruple insertion. The hope is that the insight contained in the review will aid in applying protic and Lewis acid-activated isocyanide insertions to prepare an array of complex heterocycles.

Irradiation of a toluene solution containing cyclopentadienone tricarbonyl iron complexes and isocyanides with blue LEDs afforded the formation and isolation of 12 triisocyanide complexes, two of which, namely tris(2,6-dimethylphenyl isocyanide)(η4-tetraphenylcyclopenatedienone)iron, [Fe(C9H9N)3(C29H20O)], and tris(naphthalen-2-yl isocyanide)(η4-tetraphenylcyclopenatedienone)iron acetone hemisolvate, [Fe(C11H7N)3(C29H20O)]2·C3H6O, could be characterized crystallographically. The air-stable compounds were purified by column chromatography and were characterized by 1H NMR, 13C NMR, elemental analysis and HRMS. NMR and XRD data indicate generally more electron-rich Fe0 centers compared to the corresponding tricarbonyl compounds.

Herein, a copper‐catalyzed photoinduced [3+3] cycloaddition reaction of α‐acidic isocyanides with 2,5‐diaryltetrazoles is described. The reaction proceeded smoothly with high regioselectivity, affording a range of important 1,2,4‐triazines under mild conditions. The obtained 1,2,4‐triazines were converted into triazine alcohol, Weinreb amide and triazinone easily, which further illustrate the utility of this [3+3] cycloaddition process. [ABSTRACT FROM AUTHOR]

Ag/Fe3O4/SiO2@MWCNTs MNCs magnetic nanocomposites as an effective catalyst was employed for generating of imidazopyrimidine derivatives in high yields. The structure of synthesized nanoatalyst was confirmed by SEM, XRD, TEM, VSM, EDX and XPS analysis. These new compounds were synthesized by using multicomponent reaction of cyclic guanidine derivatives, electron deficient acetylenic compounds, tert‐butyl isocyanide, ethyl bromopyruvate and synthesized nanocatalyst in aqueous media at room temperature. It should be mentioned that the high performance of nanocatalyat was synthesized by using water extract of Petasits hybridus leaves, which was utilized in these reactions for many times to confirm the reusability of nanocatalyst. The antioxidant property of new synthesized imidazopyrimidine was evaluated by two procedures and compound 5 b have the high property relative to other compounds. Also, the antimicrobial activity of new generated imidazopyrimidine was evaluated by disk distribution process utilizing two kinds of Gram‐negative bacteria and Gram‐positive bacteria; proving bacterial growth was stopped by using of these compounds. Also, to better understanding reaction mechanism density functional theory (DFT) based quantum chemical methods have been applied. Applied to the preparation of imidazopyrimidine derivatives, this method has short reaction times, high product yields, and the ability to separate catalyst and product using simple procedures. [ABSTRACT FROM AUTHOR]

This paper describes the development of 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylate compound as a heterocyclic enols containing a Michael acceptor so that it participates in an Ugi-type multicomponent condensation through a Smiles rearrangement in replacement of acid components. The new four-component containing 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxylate, aldehyde derivatives, amine derivatives and isocyanides process leads readily and efficiently to heterocyclic enamines. This report is an outstanding strategy for the preparation of new biologically structures containing peptidic or pseudo-peptidic with quinolin-2(1H)-one scaffolds. [ABSTRACT FROM AUTHOR]

Peptidomimetics with a substituted imidazo[1,2-a]pyridine fragment were synthesized by a tandem of Groebke–Blackburn–Bienaymé and Ugi reactions. The target products contain substituted imidazo[1,2-a]pyridine and peptidomimetic moieties as pharmacophores with four diversity points introduced from readily available starting materials, including scaffold diversity. A small focused compound library of 20 Ugi products was prepared and screened for antibacterial activity.

The C−C bond formation between C1 molecules plays an important role in chemistry as manifested by the Fischer–Tropsch (FT) process. Serving as models for the FT process, we report here the reactions between a neutral AlI complex (MeNacNac)Al (1, MeNacNac=HC[(CMe)(NDipp)]2, Dipp=2,6‐diisopropylphenyl) and various isocyanides. The step‐by‐step coupling mechanism was studied in detail by low‐temperature NMR monitoring, isotopic labeling, as well as quantum chemical calculations. Three different products were isolated in reaction of 1 with the sterically encumbered 2,6‐bis(benzhydryl)‐4‐Me‐phenyl isocyanide (BhpNC). These products substantiate carbene intermediates. The reaction between 1 and adamantyl isocyanide (AdNC) generated a trimerization product, and a corresponding carbene intermediate could be trapped in the form of a molybdenum(0) complex. Tri‐, tetra‐, and even pentamerization products were isolated with the sterically less congested phenyl and p‐methoxyphenyl isocyanides (PhNC and PMPNC) with concurrent construction of quinoline or indole heterocycles. Overall, this study provides evidence for carbene intermediates in FT‐type chemistry of aluminium(I) and isocyanides. [ABSTRACT FROM AUTHOR]

Im Fischer–Tropsch (FT) Prozess werden C−C Bindungen zwischen C1 Bausteinen geknüpft. Die Knüpfung solcher C−C Bindungen ist von großem Interesse in vielen Katalysezyklen. In dieser Arbeit beschreiben wir die Reaktion zwischen dem neutralen AlI Komplex (MeNacNac)Al (1, MeNacNac=HC[(CMe)(NDipp)]2, Dipp=2,6‐diisopropylphenyl) und verschiedenen Isocyaniden, welche somit als Modelle für den FT‐Prozess dienen. Der Stufenmechanismus wurde mittels Tieftemperatur NMR Monitoring, Isotopenmarkierung sowie quantenchemischen Rechnungen untersucht. Drei verschiedene Produkte konnten nach der Reaktion von 1 mit dem sterisch anspruchsvollen 2,6‐bis(Benzhydryl)‐4‐Me‐Phenyl Isocyanid (BhpNC) isoliert werden und belegen transiente Carbenintermediate. Die Reaktion von 1 mit Adamantylisocyanid (AdNC) ergab ein Trimerisierungsprodukt, wobei ein Carbenintermediat in Form eines Mo0 Komplexes abgefangen werden konnte. Tri‐, Tetra‐, sowie Pentamerisierungsprodukte wurden mit den sterisch weniger anspruchsvollen Phenyl‐ und p‐Methoxyphenylisocyaniden (PhNC und PMPNC) unter Ausbildung von Quinolin‐ und Indolheterozyklen erhalten. Diese Arbeit belegt Carbenintermediate in der FT‐Chemie von AlI mit Isocyaniden. [ABSTRACT FROM AUTHOR]

Three neutral Cu(I) complexes bearing 2,6‐dimethylphenyl isocyanide (CNXyl) and different triatomic pseudohalogens (SCN−, OCN− and N3−) as ligands were efficiently synthesized and characterized. The solid‐state structures were unambiguously determined through single‐crystal X‐ray diffraction, revealing unexpected bridging coordination modes in the case of OCN− and N3−. All the complexes were tested for azide‐alkyne cycloaddition (CuAAC), showing interesting catalytic activity towards the formation of 1,4‐disubstituted‐1,2,3‐triazoles for the cyanato and the azido Cu(I) complexes. Both species afforded yields above 90% with 0.5 mol% of catalyst at 50°C for 24 h. Several alkynes and azides were tested using the more active azido Cu(I) complex, affording the corresponding triazoles in high yields. The azido Cu(I) complex also induced the intramolecular CuAAC in the presence of dimethyl acetylenedicarboxylate and benzyl bromide/phenylacetylene. [ABSTRACT FROM AUTHOR]

α-Ketoamide moieties, as privileged units, may represent a valuable option to develop compounds with favorable biological activities, such as low toxicity, promising PK and drug-like properties. An efficient silver-catalyzed decarboxylative acylation of α-oxocarboxylic acids with isocyanides was developed to derivatize the α-ketoamide functional group via a multicomponent reaction (MCR) cascade sequence in one pot. A series of α-ketoamides was synthesized with three components of isocyanides, aromatic α-oxocarboxylic acid analogues and water in moderate yields. Based on the research, the silver-catalyzed decarboxylative acylation confirmed that an oxygen atom of the amide moiety was derived from the water and air as a sole oxidant for the whole process. [ABSTRACT FROM AUTHOR]

Irradiation of a toluene solution containing cyclopentadienone tricarbonyl iron complexes and isocyanides with blue LEDs afforded the formation and isolation of 12 triisocyanide complexes, two of which, namely tris(2,6-dimethylphenyl isocyanide)(ν4-tetraphenylcyclopenatedienone)iron, [Fe(C9H9N)3(C29H20O)], and tris(naphthalen-2-yl isocyanide)(ν4-tetraphenylcyclopenatedienone)iron acetone hemisolvate, [Fe(CnH7N)3(C29H20O)]2-C3H6O, could be characterized crystallographically. The air-stable compounds were purified by column chromatography and were characterized by 1HNMR, 13C NMR, elemental analysis and HRMS. NMR and XRD data indicate generally more electron-rich Fe0 centers compared to the corresponding tricarbonyl compounds. [ABSTRACT FROM AUTHOR]

Isocyanides have been extensively utilized in organic synthesis to construct valuable chemical structures. Classical Ugi 4‐component reaction is the robust method to access diversely functionalized peptoids. By using well‐established cyclization techniques, a variety of nitrogen heterocycles from commercially accessible compounds have been efficiently synthesized. Several transition metal‐catalyzed processes have been developed to utilize isocyanide as a useful carbonyl nitrogen synthon. Recently developed synthetic methods, such as C–H bond activation and visible‐light photocatalysis, have been adopted to the isocyanide chemistry to enhance the efficiency, availability, and novelty of the chemical processes. This review summarizes the reactivity of isocyanide classified by the activation modes of electrophilic, nucleophilic, and radical species, together with the seminal discoveries and recent advances in the past 10 years. [ABSTRACT FROM AUTHOR]

Multicomponent reactions (MCR) have been used to synthesize a wide range of analogs from several classes of heterocyclic compounds, with multifaceted medicinal uses. The synthesis of highly functionalized molecules in a single pot is a unique property of MCR, allowing researchers to quickly assemble libraries of compounds of biological interest and uncover novel leads as possible therapeutic agents. Isocyanide-based multicomponent reactions have proven to be extremely effective at swiftly specifying members of compound libraries, particularly in the discovery of drugs. The understanding of structure–activity correlations that drive the development of new goods and technology requires structural variety in these libraries. In today's world, antibiotic resistance is a major ongoing problem that poses risks to public health. The implementation of isocyanide-based multicomponent reactions upholds a significant potential in this regard. By utilizing such reactions, new antimicrobial compounds can be discovered and subsequently used to fight against such concerns. This study discusses the recent developments in antimicrobial medication discovery using isocyanide-based multicomponent reactions (IMCRs). Furthermore, the article emphasizes the potential of IMCRs (Isocyanide-based multicomponent based reactions) in the near future. [ABSTRACT FROM AUTHOR]

The kinetically unstable propargylisocyanide was reacted with the tetrakis(acetonitrile) copper(I) hexafluorophosphate and the formed complex was then involved in a copper-catalyzed alkyne-azide cycloaddition reaction (CuAAC). After the decomplexation of the adduct, the isocyanide was engaged in a Ugi reaction. By such a complexation, reactions can be carried out on the CC triple bond without the constraint of the instability of the free compound or the competitive reactivity of the isocyanide group. [ABSTRACT FROM AUTHOR]

Isocyanides are hardly produced, dramatically sensitive to purification processes, and complex to handle as synthetic tools. Notwithstanding, they represent one of the most refined and valuable compounds for accessing sophisticated and elegant synthetic routes. A unique interest has always been addressed to their production, though their synthetic pathways usually involve employing strong conditions and toxic reagents. The current paper intends to provide a conceptually innovative synthetic protocol for mechanochemical isocyanide preparation, simultaneously lowering the related reagents' toxicity and improving their purification in a straightforward procedure.

The kinetically unstable propargylisocyanide was reacted with the tetrakis(acetonitrile) copper(I) hexafluorophosphate and the formed complex was then involved in a copper-catalyzed alkyne-azide cycloaddition reaction (CuAAC). After the decomplexation of the adduct, the isocyanide was engaged in a Ugi reaction. By such a complexation, reactions can be carried out on the CC triple bond without the constraint of the instability of the free compound or the competitive reactivity of the isocyanide group.

An iron‐catalysed carbene transfer reaction of diazo compounds to isocyanides has been developed. The resulting ketenimines are trapped in situ with various bisnucleophiles to access a range of densely functionalized heterocycles (pyrimidinones, dihydropyrazolones, 1H‐tetrazoles) in a one‐pot process. The electron‐rich Hieber anion ([Fe(CO)3NO]−) facilitates efficient catalytic carbene transfer from acceptor‐type α‐diazo carbonyl compounds to isocyanides, providing a cost‐efficient and benign alternative to similar noble metal‐catalysed processes. Based on DFT calculations a plausible reaction mechanism for activation of the α‐diazo carbonyl carbene precursor and ketenimine formation is provided. [ABSTRACT FROM AUTHOR]

Isocyanide is an important class of active synthon with a special electronic structure and abundant chemical properties, which can participate in various organic reactions and has a wide range of applications in the efficient synthesis of pharmaceutical molecules, heterocyclic compounds, and natural products, etc. With the development of chemical science, isocyanide‐based reactions have been gradually applied from the synthesis of low mass molecules to functional polymers. This review focuses on the recent progress in isocyanide‐based step‐growth polymerization, as well as the properties and applications of the resultant functional polymers. These polymerizations are divided into six main parts including Passerini polymerization, Ugi polymerization, multicomponent polymerization (MCP) of isocyanide and dialkylacetylenedicarboxylates (DAADs), MCP of isocyanide and green monomer, MCP of isocyanide and industrial waste, as well as the polymerization based on isocyanoacetate. The existing challenges and the promising opportunities are concisely discussed. [ABSTRACT FROM AUTHOR]

5-(Alkylamino)-6-aryl/alkylpyrazine-2,3-dicarbonitriles were successfully synthesized in good to moderate yields by reacting alkyl isocyanides with aryl/alkyl carbonyl chlorides, followed by the addition of diaminomaleonitrile. The synthesized pyrazines were fully characterized in this investigation, and X-ray crystal structure analysis was performed on some derivatives. The antibacterial and antifungal activities of the newly synthesized pyrazine-2,3-dicarbonitriles were assessed in addition to their UV and fluorescence results. All the compounds showed similar UV–Vis spectral features with absorption peaks (λmax) around 267, 303, and 373 nm. [ABSTRACT FROM AUTHOR]

Reaction rate acceleration using green methods is an intriguing area of research for chemists. In this regard, water as a "green solvent" plays a crucial role in the acceleration of some organic transformations and reveals exclusive selectivity and reactivity in comparison with conventional organic solvents. In particular, multicomponent reactions (MCRs) as sustainable tools lead to the rapid generation of small-molecule libraries in water and aqueous media due to the prominent role of the hydrophobic effect. MCRs, as diversity-oriented synthesis (DOS) methods, have great efficiency with simple operations, atom, pot, and step economy synthesis, and mechanistic beauty. Among diverse classes of MCRs, isocyanide-based multicomponent reactions (I-MCRs), as sustainable and versatile reactions, have gained considerable attention in the synthesis of diverse heterocycle rings, especially in drug design because of the peculiar nature of isocyanide as a particular active reactant. I-MCRs that are performed in water are mild, environmentally friendly, and easily controlled, and have a reduced number of workup, purification, and extraction steps, which fit well with the advantages of "green" chemistry. Performing these powerful organic transformations in water and aqueous media is accompanied by acceleration owing to negative activation volumes, which originate from connecting several reactants together to generate a single product. It should be noted that the combination of MCR strategy and aqueous phase reaction is of growing interest for the development of sustainable synthetic techniques in organic conversions. However, an exclusive account focusing on the recent progress in eco-friendly I-MCRs for the construction of heterocycles in water and aqueous media is particularly lacking. This review highlights the progress of various kinds of I-MCRs in water and aqueous media as benign methods for the efficient construction of vital heterocyclic scaffolds, with a critical discussion of the subject in the period 2000–2021. We hope that this themed collection will be of interest and beneficial for organic and pharmaceutical chemists and will inspire more reaction development in this fascinating field. [ABSTRACT FROM AUTHOR]

The electron-rich isonitrile is an important functionality in bioactive natural products, but its biosynthesis has been restricted to the IsnA family of isonitrile synthases. We herein provide the first structural and biochemical evidence of an alternative mechanism for isonitrile formation. ScoE, a putative non-heme iron(II)-dependent enzyme from Streptomyces coeruleorubidus, was shown to catalyze the conversion of (R)-3-((carboxymethyl)amino)butanoic acid to (R)-3-isocyanobutanoic acid through an oxidative decarboxylation mechanism. This work further provides a revised scheme for the biosynthesis of a unique class of isonitrile lipopeptides, of which several members are critical for the virulence of pathogenic mycobacteria.

The synthesis of sterically hindered α‐arylated acetamides generally requires a multistep reaction sequence and is also difficult to access due to steric constraints. This protocol allows the synthesis of sterically hindered α‐arylated acetamides in moderate to high yields via 1,6‐addition of isocyanides to p‐quinone methides in the presence of BF3.OEt2. The present transformation features transition metal‐free conditions, avoiding the use of toxic carbon monoxide, broad substrate scope, mild reaction conditions, and operational simplicity. [ABSTRACT FROM AUTHOR]

A facile and efficient method is presented for the synthesis of 6‐alkylated phenanthridine, possessing hindered quaternary carbon centers, by Zn‐mediated reductive trapping of tertiary alkyl radicals with both electron‐rich and electron‐deficient aryl isocyanides using nickel as a promoter. Bench‐stable and operation‐friendly tertiary alkyl oxalates derived from abundant tertiary alkyl alcohols were first used as radical precursors for the alkylation of isocyanobiphenyl species. This reaction displays excellent functional group tolerance and broad substrate scope, allowing access to desired products in good to excellent yields. [ABSTRACT FROM AUTHOR]

As the recent outbreak of coronavirus disease 2019 (COVID-19) has shown, viral infections are prone to secondary complications like invasive aspergillosis with a high mortality rate, and therefore the development of novel, effective antifungals is of paramount importance. We have previously demonstrated that 1-amino-5-isocyanonaphthalene (ICAN) derivatives are promising original drug candidates against Candida strains (Patent pending), even against fluconazole resistant C. albicans. Consequently, in this study ICANs were tested on Aspergillus fumigatus, an opportunistic pathogen, which is the leading cause of invasive and systematic pulmonary aspergillosis in immunosuppressed, transplanted and cancer- or COVID-19 treated patients. We have tested several N-alkylated ICANs, a well as 1,5-naphthalene-diisocyanide (DIN) with the microdilution method against Aspergillus fumigatus strains. The results revealed that the diisocyanide (DIN) was the most effective with a minimum inhibitory concentration (MIC) value as low as 0.6 µg mL−1 (3.4 µM); however, its practical applicability is limited by its poor water solubility, which needs to be overcome by proper formulation. The other alkylated derivatives also have in vitro and in vivo anti-Aspergillus fumigatus effects. For animal experiments the second most effective derivative 1-N, N-dimethylamino-5-isocyanonaphthalene (DIMICAN, MIC: 7–8 µg mL−1, 36–41 µM) was selected, toxicity tests were made with mice, and then the antifungal effect of DIMICAN was tested in a neutropenic aspergillosis murine model. Compared to amphotericin B (AMB), a well-known antifungal, the antifungal effect of DIMICAN in vivo turned out to be much better (40% vs. 90% survival after eight days), indicating its potential as a clinical drug candidate. [ABSTRACT FROM AUTHOR]

We report here an isocyanide‐based multicomponent reaction to assemble a number of tricyclic chromenopyrrole derivatives with diastereoselectivity. Mechanistically, this protocol employs phenol as electron‐rich species, thus following bicyclization process to approach a series of diverse structures. [ABSTRACT FROM AUTHOR]

Spiro-heterocyclic indolenines are privileged scaffolds widely present in numerous indole alkaloids. Here, we develop a novel approach for the one-pot multistep synthesis of different spiro[indole-isoquinolines]. The protocol proposed involves the visible light mediated oxidation of N -aryl tertiary amines using bromochloroform with the generation of a reactive iminium species, which reacts with an isocyanide and an electron-rich aniline in a three-component Ugi-type reaction to give an α-aminoamidine. This compound might undergo an additional visible light-mediated oxidation to furnish a second iminium intermediate, which acts as electrophile in an intramolecular electrophilic aromatic substitution giving the final spiro-indolenine. The scope of the process has been investigated with respect to all three components. Simple operations, mild conditions, and good yields make this strategy a convenient and sustainable way to obtain novel spiro-indolenine derivatives., (Copyright © 2024, Gambuti et al.)

α-Ketoamide moieties, as privileged units, may represent a valuable option to develop compounds with favorable biological activities, such as low toxicity, promising PK and drug-like properties. An efficient silver-catalyzed decarboxylative acylation of α-oxocarboxylic acids with isocyanides was developed to derivatize the α-ketoamide functional group via a multicomponent reaction (MCR) cascade sequence in one pot. A series of α-ketoamides was synthesized with three components of isocyanides, aromatic α-oxocarboxylic acid analogues and water in moderate yields. Based on the research, the silver-catalyzed decarboxylative acylation confirmed that an oxygen atom of the amide moiety was derived from the water and air as a sole oxidant for the whole process.

In this research, a new bio multilayered nanostructure based on commercial nanomagnetite has been prepared. Gradually the silica and D-leucine amino acid, as the bio part, anchored on the surface of nano Fe3O4 followed by functionalization step, accomplished with chlorosulfonic acid. This bio-nano organic–inorganic core-shell hybrid (nano SO3H-D-Leu@SiO2-Fe3O4) characterized by FESEM, EDAX, FT-IR, TGA/DTG, TEM, VSM, and XRF techniques. Its efficient catalytic activity examined for the synthesis of 7,7'-((aryl/alkyl)methylene)bis(N-cyclohexyl-2-(aryl/alkyl)-6-methyl-3H-imidazo[1,2-b]pyrazol-3-imine) derivatives through a pseudo-seven component one-pot and one-step reaction of various aldehydes, 3-amino-5-methylpyrazole, and cyclohexyl isocyanide in ethanol solvent at room temperature with excellent yields. The condensed products obtained via construction of various new C-C and C = N bonds. The interpreted protocol included advantages, such as easy preparation approach for nano-sized bio core-shell organic–inorganic hybrid, short reaction times, simple work-up process due to separation of the catalyst by an external magnet, recovery, and reusability of the nanocatalyst for three runs without notable activity loss (the recovered nanostructure characterized by FESEM and EDAX techniques), utilizing different class of aldehydes successfully, and regioselectivity of the procedure. [ABSTRACT FROM AUTHOR]

A general method is developed to allow de novo construction of quinolines and C2‐functionalized quinolines from ortho‐alkenyl anilines in the presence of a difluorocarbene precursor. This method exploits a crucial reactivity of in‐situ generation of isocyanides from condensation of primary aniline with difluorocarbene. Subsequent α‐addition of isocyanide by neighbouring alkenyl group constructs the quinoline ring. Furthermore, when a combination of difluorocarbene precursor and Se are present, selenoisocyanate intermediates are tentatively generated that upon nucleophilic addition by ortho‐alkenyl produce 2‐SeH quinolines. In the presence of a second nucleophile such as anilines, competing nucleophilic addition of anilines to the selenoisocyanate is preferred, generating selenourea intermediate. Further nucleophilic addition of the ortho‐alkenyl to selenourea followed by elimination of H2Se produces 2‐aminoquinolines. This allows one‐step multi‐component modular preparation of various C2‐functionalized quinolines from readily available starting compounds. This method shows good yields, scope and chemoselectivity. It is operationally convenient and friendly without manipulating unpleasant isocyanides. The difluorocarbene‐enabled primary amine to isocyanide conversion may be exploited to develop other interesting reactions. [ABSTRACT FROM AUTHOR]