Oligosubstituted Pyrroles Directly from Substituted Methyl Isocyanides and Acetylenes

The formal cycloaddition of α‐metallated methyl isocyanides 1 onto the triple bond of electron‐deficient acetylenes 2 represents a direct and convenient approach to oligosubstituted pyrroles 3 . The scope and limitations of this reaction (24 examples, 25–97 % yield) are reported along with an optimization of the reaction conditions and a rationalization of the mechanism. In addition, a related newly developed Cu^I‐mediated synthesis of 2,3‐disubstituted pyrroles by the reaction of copper acetylides derived from unactivated terminal alkynes with substituted methyl isocyanides is described (11 examples, 5–88 %yield).     

Urea Synthesis from Isocyanides and O-Benzoyl Hydroxylamines Catalyzed by a Copper Salt

In the presence of CuOAc, a series of unsymmetric ureas can be generated in moderate to good yields under mild reaction conditions (10 mol% of CuOAc, 2 equiv t-BuONa or PhONa, 30 °C), using aryl isocyanides and O-benzoyl hydroxylamines as the readily accessible starting materials. The reactions might undergo a cascade process involving isocyanide insertion into the N-O bond and Mumm-type rearrangement. This work represents a rare example of isocyanide insertion into N-O bonds, which would extend isocyanide insertion chemistry.     

Silver‐Catalyzed Cross‐Coupling of Propargylic Alcohols with Isocyanides: An Atom‐Economical Synthesis of 2,3‐Allenamides

Cross‐coupling reactions between propargylic alcohols and isocyanides, by means of silver catalysis, have been described. This new reaction is both atom and step efficient and is applicable to a broad scope of substrates, allowing the synthesis of a range of synthetically valuable 2,3‐allenamides in moderate to excellent yields.     

Three-Component Reactions of 3-Arylidene-3H-Indolium Salts,Isocyanides and Amines

A multicomponent reaction of isocyanides with aryl(indol-3-yl)methylium salts and amines has been found. A series of aryl(indol-3-yl)acetimidamides was obtained in up to 96% yields. In the case of ethyl isocyanoacetate, the reaction is followed by cyclization to form 3,5-dihydro-4H-imidazol-4-one derivatives.     

Silver‐Catalyzed Cross‐Coupling of Isocyanides and Active Methylene Compounds by a Radical Process

Isocyanides are versatile building blocks, and have been extensively exploited in C? H functionalization reactions. However, transition‐metal‐catalyzed direct C? H functionalization reactions with isocyanides suffer from over‐insertion of isocyanides. Reported herein is a radical coupling/isomerization strategy for the cross‐coupling of isocyanides with active methylene compounds through silver‐catalysis. The method solves the over‐insertion issue and affords a variety of otherwise difficult to synthesize β‐aminoenones and tricarbonylmethanes under base‐ and ligand‐free conditions. This report presents a new fundamental C? C bond‐forming reaction of two basic chemicals.     

Sustainable Three‐Component Synthesis of Isothioureas from Isocyanides,Thiosulfonates, and Amines

Multiple applications of isothioureas as fine chemicals (or their precursors) are known, but a general sustainable method for their synthesis was hitherto unavailable. We report a novel general approach towards S‐alkyl and S‐aryl isothioureas through a copper(I)‐catalyzed three‐component reaction between amines, isocyanides, and thiosulfonates. The formal synthesis of a superpotent sweetener further illustrates the applicability of our method.     

Radical Fluoroalkylation of Isocyanides with Fluorinated Sulfones by Visible‐Light Photoredox Catalysis

The radical fluoroalkylation of isocyanides with fluorinated sulfones is enabled by visible‐light photoredox catalysis. A wide range of readily available mono‐, di‐, and trifluoromethyl heteroaryl sulfones can thus be used as efficient radical fluoroalkylation reagents under mild conditions. This method not only describes a new synthetic application of fluorinated sulfones, but also provides a new route to fluoroalkyl radicals.     

Palladium‐Catalyzed Migratory Insertion of Isocyanides: An Emerging Platform in Cross‐Coupling Chemistry

Isocyanides have been important building blocks in organic synthesis since the discovery of the Ugi reaction and related isocyanide‐based multicomponent reactions. In the past decade isocyanides have found a new application as versatile C₁ building blocks in palladium catalysis. Palladium‐catalyzed reactions involving isocyanide insertion offer a vast potential for the synthesis of nitrogen‐containing fine chemicals. This Minireview discusses all the achievements in this emerging field.     

The Diverse Reactivity of Disilenes Toward Isocyanides

The addition of 2,6‐dimethylphenyl isocyanide and t‐butyl isocyanide to tetramesityldisilene was examined. In both cases, the initially formed product is an iminodisilirane; however, the iminodisiliranes are unstable under the reaction conditions and react with a second equivalent of the isocyanide to give either a 3‐silaazetidine or a novel bicyclic double enamine, respectively. Taken together with the previous examples in the literature, the results demonstrate that subtle differences in the steric bulk of the disilene or the electronic effects of the isocyanide can lead to dramatic differences in the reaction pathway.     

Insertion of Isocyanides into N−Si Bonds: Multicomponent Reactions with Azines Leading to Potent Antiparasitic Compounds

Trimethylsilyl chloride is an efficient activating agent for azines in isocyanide‐based reactions, which then proceed through a key insertion of the isocyanide into a N?Si bond. The reaction is initiated by N activation of the azine, followed by nucleophilic attack of an isocyanide in a Reissert‐type process. Finally, a second equivalent of the same or a different isocyanide inserts into the N?Si bond leading to the final adduct. The use of distinct nucleophiles leads to a variety of α‐substituted dihydroazines after a selective cascade process. Based on computational studies, a mechanistic hypothesis for the course of these reactions was proposed. The resulting products exhibit significant activity against Trypanosoma brucei and T. cruzi, featuring favorable drug‐like properties and safety profiles.     

Unusual condensation ofN-phenylsemiquinonediimine ligands coordinated to the NiII atom with an acetone molecule to form a heterocycle

The reaction of a mononuclear Ni^II semiquinonediimine complex,viz., Ni[1,2-(NPh)(NH)C₆H₄]₂, with silver triflate was investigated. The starting monomer was not oxidized in benzene or CH₂Cl₂ solutions; instead, a solvate of the complex with C₆H₆ was formed. According to the X-ray diffraction data, the solvate is characterized by an unusual molecular packing with short C−H(C₆H₆)... Ni and C−H(C₆H₆)... N−H contacts. An analogous effect is observed in the crystals of the solvate Pt[1,2-(NPh)(NH)C₆H₄]₂·C₆H₆. Grinding of the nickel complex with silver triflate (the reagent ratio was 1:5) in the presence of acetone led to the oxidation of the complex, yielding tetrahydroimidazophenazinium triflate, whose structure was established by X-ray diffraction analysis. Published inIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1794–1798, October, 2000.     

The Mitsunobu reaction in the chemistry of nitrogen-containing heterocyclic compounds. The formation of heterocyclic systems (review)

Methods for the design of nitrogen-containing heterocyclic systems involving the formation of C-N bonds under the conditions of the Mitsunobu reaction are discussed. Dedicated to Afanasi Andreevich Akhrem on his 95th birthday. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 347–385, March, 2008.     

Isocyanides in the synthesis of nitrogen heterocycles

Isocyanides have long proved themselves to be irreplaceable building blocks in modern organic chemistry. The unique features of the isocyano group make isocyanides particularly useful for the synthesis of a number of important classes of nitrogen heterocycles, such as pyrroles, indoles, and quinolines. Several cocyclizations of isocyanides via zwitterions and radical intermediates as well as transition-metal-catalyzed syntheses of different types of heterocycles have recently been developed. Methods starting from isocyanides often have distinct advantages over alternative approaches to the same heterocycles because of their enhanced convergence, the great simplicity of most of the operations with them, and the great variety of isocyanides readily available for use. Isocyanides have also been used in some enantioselective syntheses of chiral heterocyclic compounds, including natural products as well as precursors thereof.     

Gas‐Phase Infrared Spectra of Three Compounds of Astrochemical Interest: Vinyl,Allenyl, and Propargyl Isocyanides

Isocyanides, isomers of the cyanides detected in the interstellar medium, are also possible components of this medium. The infrared spectra (5000–500 cm^?1) of gaseous vinyl isocyanide, allenyl isocyanide, and propargyl isocyanide have been recorded at 0.1 cm^?1 resolution. When prepared on a gram scale to produce a partial pressure of 10 mbar after evaporation in the cell, these three isocyanides, which have previously been reported to be kinetically unstable, do not display any sign of decomposition when recording the spectra. Geometry optimizations and harmonic and anharmonic vibrational frequencies were calculated using the LCCSD(T) method with the cc‐pVTZ basis set. Anharmonic frequencies of fundamental, overtone, and combination transitions were calculated using a variational approach implemented in the P Anhar.v2.0 code, to assign the experimental data for each compound. These results improve our knowledge of these under‐investigated compounds and pave the way for other physicochemical studies on functionalized isocyanides.     

Atom‐Economic Silver‐Catalyzed Difunctionalization of the Isocyano Group with Cyclic Oximes: Towards Pyrimidinediones

An unprecedented silver‐catalyzed difunctionalization of the isocyano group with cyclic oximes is described. This method allows efficient and atom‐economic assembly of a vast array of structurally novel and interesting pyrimidinediones, and tolerates a range of functionalities. The resulting products can be easily converted into some useful compounds. Furthermore, the method can also be applied for the late‐stage modification of a few biologically active molecules.     

Cyanides,Isocyanides, and Hydrides of Zn,Cd and Hg from Metal Atom and HCN Reactions: Matrix Infrared Spectra and Electronic Structure Calculations

Zinc and cadmium atoms from laser ablation of the metals and mercury atoms ablated from a dental amalgam target react with HCN in excess argon during deposition at 5 K to form the MCN and MNC molecules and CN radicals. UV irradiation decreases the higher energy ZnNC isomer in favor of the lower energy ZnCN product. Cadmium and mercury atoms produce analogous MCN primary molecules. Laser ablation of metals also produces plume radiation which initiates H-atom detachment from HCN. The freed H atom can add to CN radical to produce the HNC isomer. The argon matrix also traps the higher energy but more intensely absorbing isocyanide molecules. Further reactions with H atoms generate HMCN and HMNC hydrides, which can be observed by virtue of their C−N stretches and intense M−H stretches. Computational modeling of IR spectra and relative energies guides the identification of reaction products by providing generally reliable frequency differences within the Zn, Cd and Hg family of products, and estimating isotopic shifts using to ¹³C and ¹⁵N isotopic substitution for comparison with experimental data.     

The synthesis and structure of ferrocenylalkyl onium derivatives of nitrogen-containing heterocyclic compounds

The reactions of hydroxymethylferrocene, -hydroxyethylferrocene, and 1,1-bis(-hydroxyethyl)ferrocene withN-ferrocenylalkyl-substituted benzotriazoles, hexamethylenetetramine, and azaferrocene in the CH₂Cl₂ — 48% aqueous HBF₄ two-phase system affordedN-mono-,N-1,1-ferrocenylene-bis--alkylated, and 1,3-bis-ferrocenylalkylated tetrafluoroborates of the above-mentioned heterocyclic compounds in high yields. An X-ray structural study of 1,3-bis-(ferrocenylmethyl)benzotriazolium tetrafluoroborate confirmed unambiguously the 1,3-arrangement of the ferrocenylmethyl groups in the heterocycle.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 554–558, March, 1995.