Search

Starting from a historical background that acknowledges isonitriles as a neglected class of compounds due to their unpleasant smell and hardly controlled reaction conditions with open shell species, the present concept article aims at highlighting the seeds of the modern isonitrile photochemistry. Representative essential transformations achieved via either UV light irradiation or radical initiators at high temperatures are brought into play to draw a parallel with the current literature relying on the exploitation of visible light photochemical methods. Such a comparison points out the potential of this enabling technology to further expand the scope of isonitrile chemistry and the unmet challenges which makes it a very stimulating field. [ABSTRACT FROM AUTHOR]

Incorporation of CO into substrates to construct high‐value carbonyl compounds is an intensive industrial carbonylation procedure, however, high toxicity and wide explosion limits (12.5–74.0 vol% in air) of CO limit its application in industrial production. The development of a CO‐free catalytic system for carbonylation is one of ideal methods, but full of challenge. Herein, this study reports the CO‐free aminocarbonylation conversion of terminal alkynes synergistically catalyzed by a unique Co(ІІ)/Ag(І) metal–organic framework (MOF), in which the combination of isocyanides and O2 is employed as safe and green source of aminocarbonyl. This reaction has broad substrate applicability in terminal alkyne and isocyanides components with 100% atom economy. The bimetal MOF catalyst can be recycled at least five times without substantial loss of catalytic activities. Mechanistic investigations demonstrate that the synergistic effect between Ag(I) and Co(II) sites can efficiently activate terminal alkyne and isocyanides, respectively. Free radical capture experiments, FT‐IR analysis and theoretical explorations further reveal that terminal alkynes and isocyanides can be catalytically transformed into an anionic intermediate through heterolysis pathways. This work provides secure and practical access to carbonylation as well as a new approach to aminocarbonylation of terminal alkynes. [ABSTRACT FROM AUTHOR]

Polyamide plays a pivotal role in engineering thermoplastics. Constrained by the harsh conditions and arduous procedures for its industrial synthesis, developing facile synthesis of polyamides is still challengeable and holds profound significance. Herein, we successfully utilized water as one of the monomers to synthesize functional polyamides under ambient conditions. A powerful multicomponent polymerization of water, isocyanides, and chlorooximes was established in phosphate‐buffered saline. Soluble and thermally stable polyamides with high weight‐average molecular weights (up to 53 900) were obtained in excellent yields (up to 95 %). The polymerization exhibits unique polymerization‐induced emission characteristics, successfully converting non‐emissive monomers into unconventional emissive polymers. Notably, the resultant polyamides could undergo effective post‐modification via the hydroxyl‐yne click reaction. By incorporating various functional groups into the polyamide, its emission color could be fine‐tuned from blue to green and to red. Remarkably, the refractive index (n) of the polyamide at 589 nm could be increased from 1.6173 to 1.7227 and the Δn could be unprecedentedly as high as 0.1054 for non‐heavy atom‐containing polymers after post‐modification, and its micron‐thick films exhibited excellent transparency in the visible region. Thus, this work not only establishes a powerful polymerization toward novel polyamides but also opens up an avenue for their versatile functionalization. [ABSTRACT FROM AUTHOR]

Past decades have witnessed significant advance of isocyanides as a class of versatile organic synthons as well as their broad applications in multi-component reactions (MCRs) and other tandem reactions. Reactions involving multiple isocyanides allow the construction of molecules with further diversification and complexity, while C–H functionalization emphasizes the advantages of high atom economy, broad substrate availability and great synthetic efficiency. This promising synergistic strategy of C–H functionalization involving multiple isocyanides provides a variety of valuable synthetic methods for organic chemists' toolbox and offers considerable potential in pharmaceutical chemistry and materials science as well. The present review outlines in detail various reaction types of C–H functionalization enabled by multiple isocyanides, and the relevant mechanistic rationale is discussed. [ABSTRACT FROM AUTHOR]

Both the pyrroloindoline core and N–CF3 moiety hold significant importance in medicinal chemistry. However, to date, no instances of constructing N–CF3-containing pyrroloindolines have been reported. Herein, we present a robust and operationally simple approach to assembling such intriguing skeletons from tryptamine-derived isocyanides through a cascade sequence, which includes an oxidative trifluorination and a subsequent halogenative cyclization. Key to the success lies in the development of a facile conversion of isocyanides to N–CF3 moiety with commercially available reagents N-halosuccinimide and Et3N·HF. The protocol features mild reaction conditions, broad functional group tolerance, good to excellent yields, and high diastereoselectivities. In addition, we demonstrate that the halide substituent within the products serves as a versatile functional handle for accessing diverse C3-quaternary-substituted N–CF3-pyrroloindolines. Both the pyrroloindoline core and N–CF3 moiety hold significant importance in medicinal chemistry. Herein, the authors present a simple approach to assembling such intriguing skeletons from tryptamine-derived isocyanides through a cascade sequence, which includes an oxidative trifluorination and a subsequent halogenative cyclization. [ABSTRACT FROM AUTHOR]

Ligand exchange processes at metal complexes underpin their reactivity and catalytic applications. While mechanisms of ligand exchange at single site complexes are well established, occurring through textbook associative, dissociative and interchange mechanisms, those involving heterometallic complexes are less well developed. Here we report the reactions of a well‐defined Fe−Al dihydride complex with exogenous ligands (CO and CNR, R=Me, tBu, Xyl=2,6‐Me2C6H3). Based on DFT calculations we suggest that these reactions occur through a dyotropic rearrangement, this involves initial coordination of the exogenous ligand at Al followed by migration to Fe, with simultaneous migration of a hydride ligand from Fe to Al. Such processes are rare for heterometallic complexes. We study the bonding and mechanism of the dyotropic rearrangement through in‐depth computational analysis (NBO, IBOs, CLMO analysis, QTAIM, NCIplot, IGMH), shedding new light on how the electronic structure of the heterometallic core responds to the migration of ligands between metal sites. The dyotropic rearrangement fundamentally changes the nature of the hydride ligands, exposing new nucleophilic reactivity as evidenced by insertion reactions with CO2, isocyanates, as well as isocyanides. [ABSTRACT FROM AUTHOR]

The γ‐lactam ring is a prominent feature in medicinal chemistry, and its synthesis has garnered significant interest due to its valuable properties. Among the γ‐lactams, 2‐oxopyrrolidine‐3‐carbonitrile derivatives stand out as versatile synthons that can be readily transformed into a variety of other functional groups. In this work, we successfully synthesized highly functionalized 3‐cyano‐2‐pyrrolidinones with moderate to good overall yields using the Ugi reaction followed by intramolecular Michael addition. The process demonstrated excellent diastereoselectivity and showed good tolerance to a range of isonitriles and carbonyl compounds. [ABSTRACT FROM AUTHOR]

Comprehensive Summary The pursuit of sustainable and environmentally benign synthetic methods continues to challenge organic chemists. Herein, we introduce a magnetoredox system for tri‐ and difluoromethylation of isocyanides and N‐arylacrylamides using a rotating magnetic field and steel rods. This magnetoredox approach enables facile synthesis of functionalized phenanthridines and oxindoles without the need for catalysts and additives under mild conditions. Such a system potentially represents an attractive strategy for selective formation of bonds through multifaceted regulation of magnetic intensity, rotating frequency, and rod size. [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]

A rare conjugate addition to isocyanoalkenes with ethyl cyanoacetate triggers an efficient addition–cyclization–decarboxylation cascade. Using finely dispersed NaOH in THF as a base and nucleophile, is critical in facilitating the proton transfers, the ester hydrolysis, and the subsequent decarboxylation. The strategy provides an efficient route to valuable nitrile-substituted 2,3-dihydro-1 H -pyrroles while providing fundamental insight into conjugate additions to isocyanoalkenes. [ABSTRACT FROM AUTHOR]

A library of new neutral and cationic Ni(II) complexes containing isocyanide ligands and mono- or dialkyl-dithiophosphate have been easily prepared and fully characterized. The synthesis of the neutral complexes unfolds through the alkyl transfer from one alkyldithiophosphate leaving group coordinated to the Ni(II) complex. The alkyl transfer is controlled by steric factors and is highly solvent-dependent. These complexes shown to constitute excellent precursors to obtain new families of air stable Ni(II)-based acyclic diaminocarbene complexes (Ni(II)-ADCs) by nucleophilic attack with various alkyl-substituted amines. Remarkably, the ADC is only produced at one of the isocyanide ligands, keeping the other isocyanide unreacted. This was subsequently exploited to prepare the unprecedented neutral and cationic dinuclear Ni(II) complexes containing a bridging bis-carbene ligand using piperazine. [ABSTRACT FROM AUTHOR]

By exploiting the chemistry of bifunctional isocyanides, straightforward, rapid, and scalable Ugi-tetrazole-based multicomponent reaction heteroannulations were developed. Our synthetic approach provides a series of diverse fused tetrazolo piperazinones and 1,4-diazepanones in just one step. [ABSTRACT FROM AUTHOR]

2‐(chalcogen)benzothiazoles are frequently used as core structures for the development of pharmaceutical agents. A strategy for the synthesis of 2‐(chalcogen)benzothiazoles under electrooxidative conditions using isocyanides, thiols or diselenides as substrates was developed. This protocol allows access to structurally diverse 2‐(chalcogen)benzothiazoles in good yields and with good functional group tolerance, which does not require heavy metal catalysts and exogenous oxidants. Furthermore, gram‐scale synthesis was performed to demonstrate the scale‐up applicability of this reaction. [ABSTRACT FROM AUTHOR]

In X‐ray structures of the isomorphic mer‐[IrX3(THT)(CNXyl)2] (X=Cl 1, Br 2; THT=tetrahydrothiophene; Xyl=2,6‐Me2C6H3−) complexes, we revealed short intermolecular contacts between the C‐atom of an isocyanide methyl group and halide ligands of another molecule. Geometrical consideration of the X‐ray data and analysis of appropriate DFT studies allowed the attribution of these contacts to CMe⋅⋅⋅X−IrIII (X=Cl, Br) tetrel bond. Specifically, through the application of DFT calculations and various theoretical models, the presence of tetrel bonding interactions was validated, and the contribution of the CMe⋅⋅⋅X−IrIII interaction was assessed. The reinforcement of the tetrel bond upon the isocyanide coordination to iridium(III) is substantiated by molecular electrostatic potential (MEP) surface calculations. To distinguish the tetrel bonding characteristics of CMe⋅⋅⋅X−IrIII (X=Cl, Br) interactions from conventional hydrogen bonding, we employed multiple computational methodologies, including Natural Bond Orbital (NBO) analysis and Electron Localization Function (ELF) analysis. Additionally, Energy Decomposition Analysis (EDA) was applied to selected model systems to explore the underlying physical nature of these interactions. [ABSTRACT FROM AUTHOR]

The Groebke–Blackburn–Bienaymé (GBB) three-component reaction, discovered in 1998, is a very efficient strategy to assemble imidazo[1,2-a]-heterocycles starting from amidines, aldehydes and isocyanides. This review aims to exhaustively describe innovative aspects of this reaction achieved during the last five years, and classifies them into five categories: synthetic methods, building blocks, scaffolds, biological activities and physical properties.

A facile electrochemical synthesis of selenocarbamates from multicomponent reactions of isocyanides, diselenides, and water is developed here. This strategy provides a mild, direct, and complementary approach for synthesizing selenocarbamates in moderate to excellent yields with good substrate tolerance. The simple undivided cell setting with carbon/Pt electrodes proceeded smoothly. A radical pathway was proposed by preliminary mechanistic research. [ABSTRACT FROM AUTHOR]

A protocol exploiting isocyanides as carbamoylating agents for the α‐C(sp3)‐H functionalization of cyclic ethers has been optimized via a combined visible light‐driven hydrogen atom transfer/Lewis acid‐catalyzed approach. The isocyanide substrate scope revealed an exquisite functional group compatibility (18 examples, with yields up to 99 %). Both radical and polar trapping, kinetic isotopic effect and real‐time NMR studies support the mechanistic hypothesis and provide insightful details for the design of new chemical processes involving the generation of oxocarbenium ions. [ABSTRACT FROM AUTHOR]

An iron(III)‐promoted radical fluoroalkylation of o‐alkenylaryl isocyanides has been developed using readily available perfluoroalkyl iodides as fluoroalkyl source. This cyclization reaction features broad substrate scope and provides a simple and efficient approach for regioselective construction of biologically important 2‐fluoroalkylated quinolines in 38–81 % yields. [ABSTRACT FROM AUTHOR]

A convenient approach for synthesizing indole‐N‐carboxamide derivatives through palladium‐catalyzed isocyanide insertion into the N−H bond of 3‐(phenylhydrazono)oxindoles has been developed. The inclusion of the 3‐phenylhydrazone group proved essential in remotely activating the N−H bond of the oxindole. Also, it has been established that the reaction outcome is highly dependent on the electronic effects of the substituents. [ABSTRACT FROM AUTHOR]

Herein, we present a radical cascade addition cyclization sequence to access quinoline‐based benzophosphole oxides from ortho‐alkynylated aromatic phosphine oxides using various aryl isonitriles as radical acceptors and inexpensive tert‐butyl‐hydroperoxide (TBHP) as a terminal oxidant in the presence of a catalytic amount of silver acetate. Alternatively, the same cascade can be realized through a sustainable photochemical approach utilizing 1,2,3,5‐tetrakis(carbazol‐9‐yl)‐4,6‐dicyanobenzene (4CzIPN) as an organic photocatalyst at room temperature. The introduced modular approach shows broad functional group tolerance and offers straightforward access to complex P,N‐containing polyheterocyclic arenes. These novel π‐extended benzophosphole oxides exhibit interesting photophysical and electrochemical properties such as absorption in the visible region, emission and reversible reduction at low potentials, which makes them promising for potential materials science applications. The photophysical properties can further be tuned by the addition of external Lewis and Brønsted acids. [ABSTRACT FROM AUTHOR]

We describe the novel electrochemical multicomponent reaction (e-MCR) of readily available isocyanides, thiols and carboxylic acids to form N-substituted S-thiocarbamate derivatives that are found in several biologically active compounds. The effectiveness of the μ-electro flow reactor (μ-EFR) was showcased through significant reduction in electrolyte volume during the reaction, achieving gram-scale production of 4a within a short 12 min residence time using a Pt/Pt flow cell. [ABSTRACT FROM AUTHOR]

A silver-catalyzed chemoselective cascade nucleophilic addition of a P-centered anion to isocyanides and cyclization reaction was developed for the efficient and practical synthesis of a wide range of 2-phosphinoyl indole and indol-3-ol derivatives. Unlike the well-documented synthesis of phosphorus-functionalized heterocycles via a P-centered radical, an anionic reactivity profile of phosphine oxides is most likely involved in this domino transformation. [ABSTRACT FROM AUTHOR]

Eleven copper(I) halide complexes [CuX(CNR)3] (X = Cl, Br; R = C6H3-2,6-Cl2, C6H3-2-Cl-6-Me, C6H3-2,6-Br2, C6H3-2-Br-6-Me; X = I, R = C6H3-2,6-Cl2, C6H3-2-Cl-6-Me, C6H3-2-Br-6-Me) bearing halogen-functionalized aromatic isocyanide ligands were synthesized. The compounds were characterized by atomic emission spectroscopy (Cu), IR, 1H NMR spectroscopy and high-resolution mass spectrometry. The structure of nine compounds was determined by X-ray diffraction. Structural studies allow to reveal that the supramolecular structure of the complexes is based on weak C–H···X (X = Cl, Br, I) interactions and π-stacking of the aromatic rings of isocyanide ligands. [ABSTRACT FROM AUTHOR]

Herein, we describe a general hydrodefunctionalization protocol of alcohols and amines through a common isonitrile intermediate. To cleave the relatively inert C−NC bond, we leveraged dual hydrogen atom transfer (HAT) and photoredox catalysis to generate a nucleophilic boryl radical, which readily forms an imidoyl radical intermediate from the isonitrile. Rapid β‐scission then accomplishes defunctionalization. This method has been applied to the hydrodefunctionalization of both amine and alcohol‐containing pharmaceuticals, natural products, and biomolecules. We extended this approach to the reduction of carbonyls and olefins to their saturated counterparts, as well as the hydrodecyanation of alkyl nitriles. Both experimental and computational studies demonstrate a facile β‐scission of the imidoyl radical, and reconcile differences in reactivity between nitriles and isonitriles within our protocol. [ABSTRACT FROM AUTHOR]

The author's work in metallomesogens stemmed from initial preparations of κ1-complexes of cyanobiphenyls of the Group 10 metals, palladium and platinum. In this personalised account, these initial studies are described, put in the context of where the field was at that time and contextualised for the way the author's own contributions to the field then developed. [ABSTRACT FROM AUTHOR]

We present an Ugi multicomponent approach to explore the chemical space around Aspidosperma‐type monoterpene indole alkaloids. By variation of the isocyanide and carboxylic acid inputs we demonstrate the rapid generation of molecular diversity and the possibility to introduce handles for further modification. The key Ugi three‐component reaction showed full diastereoselectivity towards the cis‐fused ring system, which can be rationalized by DFT calculations that moreover indicate that the reaction proceeds via a Passerini‐type hydrogen bonding mechanism. Several post‐Ugi modifications were also performed, including Pictet‐Spengler cyclization to highly complex nonacyclic natural product hybrid scaffolds. [ABSTRACT FROM AUTHOR]

Synthesis of bicyclic scaffolds has emerged as an important research topic in modern drug development because they can serve as saturated bioisosters to enhance the physicochemical properties and metabolic profiles of drug candidates. Here we report a remarkably simple silver‐enabled strategy to access polysubstituted 3‐azabicyclo[3.1.1]heptanes in a single operation from readily accessible bicyclobutanes (BCBs) and isocyanides. The process is proposed to involve a formal (3+3)/(3+2)/retro‐(3+2) cycloaddition sequence. This novel protocol allows for rapid generation of molecular complexity from simple starting materials, and the products can be easily derivatized, further enriching the BCB cycloaddition chemistry and the growing set of valuable sp3‐rich bicyclic building blocks. [ABSTRACT FROM AUTHOR]

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]

Giant impacts can generate transient hydrogen-rich atmospheres, reducing atmospheric carbon. The reduced carbon will form hazes that rain out onto the surface and can become incorporated into the crust. Once heated, a large fraction of the carbon is converted into graphite. The result is that local regions of the Hadean crust were plausibly saturated with graphite. We explore the consequences of such a crust for a prebiotic surface hydrothermal vent scenario. We model a surface vent fed by nitrogen-rich volcanic gas from high-temperature magmas passing through graphite-saturated crust. We consider this occurring at pressures of 1– 1000 bar and temperatures of 1500– 1700   ∘ C . The equilibrium with graphite purifies the leftover gas, resulting in substantial quantities of nitriles ( 0.1 % HCN and 1 ppm HC3N) and isonitriles ( 0.01 % HNC) relevant for prebiotic chemistry. We use these results to predict gas-phase concentrations of methyl isocyanide of ∼1 ppm. Methyl isocyanide can participate in the non-enzymatic activation and ligation of the monomeric building blocks of life, and surface or shallow hydrothermal environments provide its only known equilibrium geochemical source. [ABSTRACT FROM AUTHOR]

Gallaphosphene L(Cl)GaPGaL 1 (L=HC[C(Me)N(Ar)]2; Ar=2,6‐iPr2C6H3) reacts with N‐heterocyclic carbenes RNHC (RNHC=[CMeN(R)]2C; R=Me, iPr) to RNHC‐coordinated phosphinidenes RNHC→PGa(Cl)L (R=Me 2 a, iPr 2 b) and with isonitriles RNC (R=iPr, Cy) to 1,3‐phosphaazaallenes L(Cl)GaP=C=N−R (R=iPr 3 a, Cy 3 b), respectively. Quantum chemical calculations reveal that 2 a/2 b possess two localized lone pair of electrons, whereas 3 a/3 b only show one localized lone pair as was reported for gallaphosphene 1. 2 b reacts with 2.5 equivalents of a borane (THF ⋅ BH3) to the NHC‐stabilized phosphinidene‐borane complex [iPrNHC→P(BH2)]2(BH3)34 with concomitant formation of LGa(H)Cl 5. 2–5 are characterized by heteronuclear (1H, 13C{1H}, 31P{1H}) NMR and IR spectroscopy, elemental analysis, and single crystal X‐ray diffraction (sc‐XRD). [ABSTRACT FROM AUTHOR]

Herein, a palladium-catalyzed and ligand-controlled protocol for the divergent synthesis of pyrrole[2,3-b]indole and urea derivatives has been described. Pyrrole[2,3-b]indoles ("cyclization on" products) via tandem cyclization of o-alkynylanilines with isocyanides in the absence of a ligand and ureas ("cyclization off" products) via oxidative amination of anilines with isocyanides in the presence of a ligand were obtained both in moderate to good yields with high selectivity. In this chemistry, cyclic and acyclic products were easily accessed with the same starting materials under the regulation of the ligand. [ABSTRACT FROM AUTHOR]

The first catalytic enantioselective [5+1] cycloaddition reactions of C,N-cyclic azomethine imines with isocyanides are reported herein. The method displays a broad substrate scope and atom-economy. A series of chiral tetrahydroisoquinoline containing indole skeletons were obtained in up to 90% yield with 95% ee under mild reaction conditions. A possible catalytic model was also proposed. [ABSTRACT FROM AUTHOR]

We describe a novel intramolecular double hydrofunctionalization cyclization of alkyne with nitrogen and oxygen nucleophilic groups to construct valuable 6/7/5-fused heterocyclic products. This post-Groebke–Blackburn–Bienaymé (GBB) reaction introduces a new class of functionalized isocyanides. Transition-metal-free cyclization, broad substrate scope, and high atom economy were some features of the present protocol. [ABSTRACT FROM AUTHOR]

Developing fluorogenic probes for simultaneous live cell labeling of multiple targets is crucial for understanding complex cellular events. The emerging [4+1] cycloaddition between tetrazine and isonitriles holds promise as a bioorthogonal tool, yet existing tetrazine probes lack reactivity and fluorogenicity. Here, we present the development of a series of tetrazine‐functionalized bioorthogonal probes. By incorporating pyrazole adducts into the fluorophore scaffolds, the post‐reacted probes displayed remarkable fluorescence turn‐on ratios, up to 3184‐fold. Moreover, these modifications are generalizable to various fluorophores, enabling a broad emission range from 473 to 659 nm. Quantum chemical calculations further elucidate the turn‐on mechanisms. These probes enable the simultaneous labeling of multiple targets in live cells, without the need for a washing step. Consequently, our findings pave the way for advanced multiplex imaging and detection techniques for cellular studies. [ABSTRACT FROM AUTHOR]

We disclose a direct approach to the diastereoselective synthesis of phosphorus substituted N-acylaziridines based on a one-pot ZnCl2-catalyzed Joullié–Ugi three-component reaction of phosphorylated 2H-azirines, carboxylic acids and isocyanides. Hence, this robust protocol offers rapid access to an array of N-acylaziridines in moderate-to-good yields and up to 98:2 dr for substrates over a wide scope. The relevance of this synthetic methodology was achieved via a gram-scale reaction and the further derivatization of the nitrogen-containing three-membered heterocycle. The diastereo- and regioselective ring expansion of the obtained N-acylaziridines to oxazole derivatives was accomplished in the presence of BF3·OEt2 as an efficient Lewid acid catalyst. [ABSTRACT FROM AUTHOR]

This microreview discusses the recent studies (last 10 years) on the synthesis of imidazo[2,1-b]thiazol-5-amines using the Groebke–Blackburn–Bienaymé multicomponent reaction between 2-aminothiazoles, isocyanides, and aldehydes under different reaction and catalytic conditions. [ABSTRACT FROM AUTHOR]

Indoles are one of the most important heterocycles because of their widespread occurrence in bioactive natural products, synthetic drugs and organic materials. Therefore, development of efficient strategies for synthesizing functionalized indoles has been of great importance in organic synthesis. Copper, being a transition metal, meet the goal due to its low toxicity, high catalytic activity and cost‐effectiveness. In this review, we focus on last five year (2019–2023) advancement in copper‐catalyzed annulations for the construction of indole core involving various N‐containing substrates, which include anilines, o‐alkynylanilines, o‐aminophenylpropynols, o‐alkynylnitroarenes, o‐nitrochalcones, azidoalkynes, isonitriles, nitriles, enamines, imines, etc. Mechanistic aspects of the reactions have also been highlighted for better understanding of the reaction pathways. [ABSTRACT FROM AUTHOR]

Reactions of a masked N‐heterocyclic phosphinidene (mNHP, 1), a four‐membered heterocycle with a divalent P atom, with various isonitriles (tBu−NC, Dmp−NC) and carbonyls (CO, Fe(CO)5, and benzalacetone) have been studied. The isonitriles (tBu−NC and Dmp−NC) insert into a P−N bond of the four‐membered ring of 1, leading to the formation of a five‐membered heterocycle (2tBu, 2Dmp), indicating carbene‐like reactivity of the isonitriles. In exactly this way, CO, which is isolobal to isonitriles, reacts to form a five‐membered ring (3) with an exocyclic C=O double bond. If, on the other hand, Fe(CO)5 is used as a CO source, a CO molecule is inserted analogously, however, the remaining Fe(CO)4 fragment is bound via a phosphorus‐iron dative bond to the five‐membered heterocycle. When mNHP 1 reacts with the α,β‐unsaturated ketone benzalacetone, phosphinidene reactivity is observed for 1. This means that the four‐membered ring opens and the P atom reacts with the benzalacetone in a cyclization reaction to form a 1,2‐oxaphospha‐cyclopentene. Theoretical studies of the five‐membered heterocycles 2 and 3 carrying eight π electrons show that zwitterionic Lewis representations dominate in the resonance scheme and only a very low biradical character (<5 %) is found. [ABSTRACT FROM AUTHOR]

A palladium‐catalyzed domino reaction of 2‐azidosulfonamides and isocyanides enables the synthesis of 3‐amino‐substituted 1,2,4‐benzothiadiazine 1,1‐dioxides at room temperature. By applying commercially available Pd(dba)2 in catalyst loadings as low as 1.0 mol%, a variety of 21 differently substituted 2H‐1,2,4‐benzothiadiazine 1,1‐dioxides can be prepared within 2 h. Moreover, the developed protocol gives access to the related 4H heterocycles. [ABSTRACT FROM AUTHOR]

Herein, we report a Pd-catalyzed multicomponent cascade reaction of 3-diazo oxindole and isocyanides to synthesize N-fused polycyclic indoles consisting of an in situ generated amide-assisted regioselective [3+1+1] annulation reaction. Additionally, a mechanism is proposed and investigated using DFT that strongly favors the role of amide in assisting the annulation reaction, which is further confirmed using control experiments. [ABSTRACT FROM AUTHOR]

Herein, we report the use of isonitriles as alkyl radical precursors in light‐mediated hydro‐ and deuterodeamination reactions. The reaction is scalable, shows broad functional group compatibility and potential to be used in late‐stage functionalization. Importantly, the method is general for Cα‐primary, Cα‐secondary and Cα‐tertiary alkyl isonitriles. For most examples, high yields were obtained through direct visible‐light irradiation of the isonitrile in the presence of a silyl radical precursor. Interestingly, in the presence of an organic photocatalyst (4CzIPN) a dramatic acceleration was observed. In‐depth mechanistic studies using UV/Vis absorption, steady‐state and time‐resolved photoluminescence, and transient absorption spectroscopy suggest that the excited state of 4CzIPN can engage in a single‐electron transfer with the isonitrile. [ABSTRACT FROM AUTHOR]

Cyanation has attracted considerable attention in organic synthesis because nitriles are key structural motifs in numerous important dyes, agrochemicals, natural products and drug molecules. As the fourth generation of cyanating reagents, isocyanides occupy a prominent place in the synthesis of nitriles due to their favorable stability, easy operability and high reactivity. In recent years, three types of cyanation with isocyanides have been established: the cleavage of the C–NC bond of tertiary alkyl isocyanides (Type I), the rearrangement of aryl isocyanides with azides (Type II), and the reductive cyanation of ketones with α-acidic isocyanides (Type III). This review focuses on advances in cyanation with isocyanides with an emphasis on reaction scope, limitations and mechanisms, which could reveal their remarkable value and superiority for accessing various nitriles. In addition, the future development prospects of this specific field are also introduced. We believe that this feature article will serve as a comprehensive tool to navigate cyanation with isocyanides across the vast area of synthetic chemistry. [ABSTRACT FROM AUTHOR]

Despite the accessibility of numerous transition metal polyphosphido complexes through transition‐metal‐mediated activation of white phosphorus, the targeted functionalization of Pn ligands to obtain functional monophosphorus species remains challenging. In this study, we introduce a new [3+1] fragmentation procedure for cyclo‐P4 ligands, leading to the discovery of acylcyanophosphanides and ‐phosphines. Treatment of the complex [K(18c‐6)][(Ar*BIAN)Co(η4‐P4)] ([K(18c‐6)]3, 18c‐6=[18]crown‐6, Ar*=2,6‐dibenzhydryl‐4‐isopropylphenyl, BIAN=1,2‐bis(arylimino)acenaphthene diimine) with acyl chlorides results in the formation of acylated tetraphosphido complexes [(Ar*BIAN)Co(η4‐P4C(O)R)] (R=tBu, Cy, 1‐Ad, Ph; 4 a–d). Subsequent reactions of 4 a–d with cyanide salts yield acylated cyanophosphanides [RC(O)PCN]− (9 a–d−) and the cyclo‐P3 cobaltate anion [(Ar*BIAN)Co(η3‐P3)(CN)]− (8−). Further reactions of 4 a–d with trimethylsilyl cyanide (Me3SiCN) and isocyanides provide insight into a plausible mechanism of this [3+1] fragmentation reaction, as these reagents partially displace the P4C(O)R ligand from the cobalt center. Several potential intermediates of the [3+1] fragmentation were characterized. Additionally, the introduction of a second acyl substituent was achieved by treating [K(18c‐6)]9b with CyC(O)Cl, resulting in the first bis(acyl)monocyanophosphine (CyC(O))2PCN (10). [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]

A series of alkynylated pyrrole derivatives were meticulously designed, drawing inspiration from the structure of 3‐alkynylpyrrole‐2,4‐dicarboxylates, which were synthesized via a cyclization process involving methylene isocyanides and propiolaldehydes under mild conditions. These derivatives were subsequently subjected to evaluation for their anticancer properties against a panel of cell lines, including U251, A549, 769‐P, HepG2, and HCT‐116. According to the detailed analysis of structure–activity relationship, compound 12l emerged as the most promising molecule, with IC50 values of 2.29 ± 0.18 and 3.49 ± 0.30 μM toward U251 and A549 cells, respectively. Subsequent mechanistic investigations revealed that compound 12l exerts its effects by arresting the cell cycle in the G0/G1 phase and inducing apoptosis specifically in A549 cells. These innovative alkynylated pyrrole derivatives hold the potential to serve as a valuable template for the discovery of novel anticancer molecules. [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]

Stefano Marcaccini was one of the pioneers in the use of isocyanide-based multicomponent reactions in organic synthesis. Throughout his career at the University of Florence he explored many different faces of isocyanide chemistry, especially those geared towards the synthesis of biologically relevant heterocycles. His work inspired many researchers who contributed to other important developments in the field of multicomponent reactions and created a school of synthetic chemists that continues today. In this manuscript we intend to review the articles on isocyanide multicomponent reactions published by Dr. Marcaccini and analyse their influence on the following works by other researchers. With this, we hope to highlight the immense contribution of Stefano Marcaccini to the development of isocyanide chemistry and modern organic synthesis as well as the influence of his research on future generations. We believe that this review will not only be a well-deserved tribute to the figure of Stefano Marcaccini, but will also serve as a useful inspiration for chemists working in this field. [ABSTRACT FROM AUTHOR]

An ultrasonic-assisted isocyanide-based protocol to access a series of functionalized spirorhodanine-cyclopentadiene and spirorhodanine-iminobutenolide conjugates from alkyl isocyanides and dialkyl acetylenedicarboxylates in the presence of 5-ylidene rhodanines in MeCN, is described. The reaction proceeds via interception of the reactive Winterfeldt's zwitterions by 5-ylidene rhodanine derivatives. The structures of the target compounds were confirmed by X-ray diffraction studies. [ABSTRACT FROM AUTHOR]

A series of gold(I) monoisocyanide [AuCl(CNC6H4-4-X)] (X = Cl (IIa), Br (IIb), I (IIc) and bis-isocyanide [Au(CNC6H4-4-X)2](PF6) (X = Cl (IIIa), Br (IIIb), I (IIIc) complexes were prepared by the reaction of [AuCl(Tht)] (Tht = tetrahydrothiophene) with the specified isocyanide. The molecular structure of IIa–IIc was established by X-ray diffraction (CCDC no. 2253450 (IIa), 2253447 (IIb), 2253448 (IIc)). The crystals of IIb and IIc are isostructural; they were found to have several types of intermolecular interactions, particularly, C–X⋯Cl–Au halogen bonds, π-hole (CCNR)··· (Au) interactions, and Au⋯Au aurophilic contacts, which form together a two-layer 2D supramolecular polymer. The crystals of IIb, IIc and IIIa, IIIb exhibit phosphorescence at room temperature; compounds IIa and IIIc do not possess luminescent properties; and mechanical grinding of IIa‒IIc and IIIa‒IIIc powders does not change the photophysical properties. [ABSTRACT FROM AUTHOR]

A three‐component 1,4‐addition variant of the Ugi reaction involving carboxylic acids, isocyanides, and cyclic α,β‐unsaturated imines is presented in this study. The cyclic α,β‐unsaturated imines were conveniently prepared through the oxidative dearomatization of N‐substituted anilines. The reaction proceeded successfully to produce a sole diastereomer, and the relative configuration was determined through 2D NMR and X‐ray diffraction analysis. [ABSTRACT FROM AUTHOR]