Alkyl Isocyanides Research Articles

ChemInform Abstract: A Simple and Efficient Approach to the Synthesis of Furopyran Derivatives: Four‐Component Reaction of Isocyanides with Arylidene‐Substituted Meldrum′s Acid.

A four-component (3+1) reaction of an alkyl isocyanide with arylidene-substituted Meldrum’s acid in CH2Cl2 at room temperature produced furo[3,4-b]pyran-5(7H)-one derivatives in good yields. The structures of the synthesized compounds were confirmed by IR, NMR spectroscopy, mass spectra, and elemental analysis.

One-pot Synthesis of Highly Functionalised 1-tosylpyrazolidines

The reactive intermediate produced in the reaction between alkyl isocyanides and dialkyl acetylenedicarboxylates has been trapped by (4-methylphenyl)sulfonyl hydrazide to yield highly functionalised 1-tosylpyrazolidines in high yields.

Synthesis of 1-Azadienes by a Three-Component Reaction between Isocyanides, Esters and 3-Hydroxy-2-Methyl-4H-Pyran-4-One

The 1: 1 reactive intermediate generated by the addition of alkyl isocyanides to dialkyl acetylenedicarboxylates was trapped by 3-hydroxy-2-methyl-4 H -pyran-4-one as OH-acid in water to yield highly functionalised 1-azadienes.

ChemInform Abstract: Synthesis of Amides by Palladium‐Catalyzed Decarbonylative Coupling of Carboxylic Acids with Isocyanides.

Amides were synthesized from carboxylic acids and isocyanides under PdII/AgI/base catalytic conditions. The reaction conditions were optimized, and the scope was studied. Various carboxylic acids and aryl isocyanides are compatible with this reaction, but alkyl isocyanides are not. A plausible mechanism, which features distinctive PdII-mediated decarbonylative coupling and unprecedented nucleophilic attack of carboxylates to PdII-ligated isocyanides, was proposed to account for this reaction.

ChemInform Abstract: An Efficient Synthesis of Dialkyl 2‐((Alkylimino)methylene)‐3‐(2‐methyl‐4‐oxoquinolin‐1(4H)‐yl)succinate Through Three Component Reaction of Alkyl Isocyanides, Dialkylacetylenedicarboxylate and 2‐Methyl‐4‐hydroxyquinoline.

ChemInform Abstract: An Efficient Synthesis of Dialkyl 2‐((Alkylimino)methylene)‐3‐(2‐methyl‐4‐oxoquinolin‐1(4H)‐yl)succinate Through Three Component Reaction of Alkyl Isocyanides, Dialkylacetylenedicarboxylate and 2‐Methyl‐4‐hydroxyquinoline.

Reaction of alkyl isocyanides and dialkyl acetylenedicarboxylates in the presence of 5,5-diaryl thiohydantoins. Synthesis of functionalized imidazo[2,1-b][1,3]thiazines

The reaction of stoichiometric amounts of dialkyl acetylenedicarboxylates with alkyl isocyanides in the presence of 5,5-diaryl thiohydantoins afforded imidazo[2,1-b][1,3]thiazines in good overall yields.

Multicomponent Reactions of Isocyanides and Dialkyl Acetylenedicarboxylate in the Presence of 2-Hydroxy-3-Methyl-2-Cyclopentene-1-One: One-Pot Synthesis of 1-Azadienes in Water

The 1: 1 reactive intermediate generated by the addition of alkyl isocyanides to dialkyl acetylenedicarboxylates was trapped by 2-Hydroxy-3-methyl-2-cyclopentene-1-one as OH-acid to yield highly functionalised 1-azadienes in water.

Cellulose@Fe2O3 nanoparticle composites: magnetically recyclable nanocatalyst for the synthesis of 3-aminoimidazo[1,2-a]pyridines

3-Aminoimidazo[1,2-a]pyridines have been synthesized through a condensation reaction of 2-aminopyridine, an aldehyde and an alkyl or aryl isocyanide in high yields in the presence of a catalytic amount of cellulose@Fe2O3 as a magnetically recoverable heterogeneous catalyst. High catalytic activity, good reusability, and simple magnetic work-up are some of the salient features of the present protocol. .

ChemInform Abstract: The Formation of Squaramic Acids and Squaryl Diamides by the Reaction of Aquaric Acid with Alkyl Isocyanides.

ChemInform Abstract: The Formation of Squaramic Acids and Squaryl Diamides by the Reaction of Aquaric Acid with Alkyl Isocyanides.

Synthesis of Highly Functionalised 1-Azadienes and Ketenimines by the Reaction of Alkyl Isocyanides and Dialkyl Acetylenedicarboxylates in the Presence of Theophylline Derivatives

* Correspondent. E-mail: mhmosslemin@gmail.com Multicomponent reactions (MCRs), by virtue of their convergence, productivity, facile execution, and generally high yields of products, have attracted attention from the point of combinatorial chemistry. Of pivotal importance in this area are the isocyanide based MCRs such as the versatile Ugi and Passerini reactions.1–4 The addition of nucleophilic carbenes such as isocyanides to dialkyl acetylenedicarboxylates has been investigated by a number of research groups.5–9 The initially formed 1:1 zwitterionic species undergo further reactions with alkyl isocyanides and dialkyl acetylenedicarboxylates, ultimately leading to a variety of complex heterocyclic systems.10,11 The reaction of 1-azadienes with various chiral dienophiles, which leads to substituted pyridines, has been reported.12,13 In the course of our work on the reaction between isocyanides and acetylenic esters,14–17 we now report an efficient synthetic route to 1-azadienes and stable ketenimines using alkyl isocyanides 1, dialkyl acetylenedicarboxylates 2, and theophylline derivatives as strong NH-acids (Scheme 1). The reaction of alkyl isocyanides 1 with acetylenic esters 2 in the presence of theophylline derivatives afforded the isomeric 1-azadienes 4 and highly functionalised ketenimines 5 in fairly good yields. However, using DTAD as the acetylenic esters, only the 1-azadiene derivative 4 was obtained (Scheme 1). Results and discussion

An Efficient Three‐Component Synthesis of Pyranoquinoline Derivatives

Pyranoquinoline derivatives have been synthesized via three‐component reaction of 4‐hydroxy‐1‐methyl‐2(1H)‐quinolinone and dialkyl acetylenedicarboxylates in the presence of nucleophiles such as alkyl isocyanides and triphenylphosphine.

Synthesis of maleate derivatives in isocyanide-base MCRs: reaction of 2-mercaptobenzoxazole with alkyl isocyanides and dialkyl acetylenedicarboxylates

Dialkyl 2-((alkylimino)(2-thioxobenzo[d]oxazol-3(2H)-yl)methyl) maleate derivatives were obtained from the reaction between alkyl isocyanides, dialkyl acetylene dicarboxylates, and 2-mercaptobenzoxazole in CH2Cl2 at room temperature in good yields.

A simple and efficient approach to the synthesis of furopyran derivatives: four-component reaction of isocyanides with arylidene-substituted Meldrum’s acid

Multicomponent reactions (MCRs) are powerful tools for the synthesis of complex biologically relevant molecules. The atom economy of MCRs, their convergent character, operational simplicity, the structural diversity [1, 2], and complexity of the resulting molecules make this type of reactions exceptionally useful for discovery and optimization processes in the pharmaceutical industry. Isocyanide-based multicomponent reactions (IMCRs) are easily performed using readily available starting materials and tolerate a variety of functional groups. A plethora of variations and subsequent transformations provide access to a fairly large number of unique structures that would otherwise require lengthy preparations. Therefore, IMCRs present an ideal tool for accessing large and diverse chemical space and have been used since the advent of combinatorial chemistry to construct such libraries of compounds [3]. During the past decade, IMCRs gained significant interest within the scientific community as an efficient, convenient, time-saving, and atom-economical approach to a variety of drug-like small heterocyclic molecules [4–12]. The furopyran skeleton is frequently found in various natural and biological products. Waol A (FD-211) has a broad spectrum of activity against cultured tumor cell lines [13]; the closely related compounds TAN-2483A and TAN-2483B show strong c-Src kinase inhibitory action and a potential for treatment and prevention of osteoporosis [14]. Antibacterial Massarilactone B was isolated by Gloer from the freshwater aquatic fungus Massarina tunicata [15]. Usually these and similar compounds are synthesized via multistep approach, often under very forcing reaction conditions [16–17]. The reactions of alkylidene- and arylidene-substituted Meldrum's acid with alkyl and aryl isocyanides have been extensively studied, and diverse products were obtained [18–21]. We have been interested in isocyanide-based multicomponent reactions and synthesis of heterocyclic skeletons [18, 20–22]. Recently, we have reported the reaction of alkylidene-substituted Meldrum's acid and isocyanide that led to new furo[3,4-b]pyran derivatives [23]. To expand this method (3+1 IMCR) for synthesis of novel furo[3,4-b]pyran derivatives, we wish to report the result of this approach for the synthesis of some novel furopyran derivatives via reaction of arylidene-substituted Meldrum's acid and isocyanides.

Synthesis and Biological Evaluation of 2-Amino-4H-pyran-3,4,5-tricarboxylate Salt Derivatives

A novel and simple method for the synthesis of 2-amino-4H-pyran-3,4,5-tricarboxylate derivative and the eval- uation of their antibacterial activity against Pseudomonas syringae, Xanthomonas citi and Pectobacterium carotovorum are reported. The structure of the isolated compounds has been determined by means of 1 H/ 13 C NMR and FT-IR Spectroscopy. The reaction of alkyl isocyanides with acetylenic esters in the presence of dimethyl acetone-1,3-dicarboxylate in the present of BF3.SiO2 at ambient temperature. Some of the compound showed significant inhibition to growth of bacteria.

Synthesis of Amides by Palladium‐Catalyzed Decarbonylative Coupling of Carboxylic Acids with Isocyanides

AbstractAmides were synthesized from carboxylic acids and isocyanides under PdII/AgI/base catalytic conditions. The reaction conditions were optimized, and the scope was studied. Various carboxylic acids and aryl isocyanides are compatible with this reaction, but alkyl isocyanides are not. A plausible mechanism, which features distinctive PdII‐mediated decarbonylative coupling and unprecedented nucleophilic attack of carboxylates to PdII‐ligated isocyanides, was proposed to account for this reaction.

Zirconium-Mediated Synthesis of Arsaalkene Compounds from Arsines and Isocyanides

An atom-economical synthesis of arsaalkenes via a net coupling of aryl arsines with aryl or alkyl isocyanides at zirconium is presented. Reaction of zirconium arsenido complexes (N3N)ZrAsHAr [N3N = N(CH2CH2NSiMe3)3(3-); Ar = Ph, (2) Mes (3)] with aryl and alkyl isocyanides yields arsaalkene products of the general form (N3N)Zr[NRC(H)═As(Ar)]. Two examples (5: R = Mes, Ar = Ph; 6: R = CH2Ph, Ar = Mes) were structurally characterized. Observation of intermediates in the reaction and structural characterization of the previously reported 1,1-insertion product benzylisocyanide with (N3N)ZrAsPh2 (8), (N3N)Zr[η(2)-C(PPh2)=NCH2Ph] (9), support the mechanistic hypothesis that these reactions occur via 1,1-insertion followed by rearrangement.

The Formation of Squaramic Acids and Squaryl Diamides by the Reaction of Squaric Acid with Alkyl Isocyanides

The reaction between squaric acid with one equivalent of alkyl isocyanides such as t-butyl isocyanide, cyclohexyl isocyanide and n-butyl isocyanide in ethanol at room temperature after 3h afforded the corresponding squaramic acid derivatives. Symmetric 2,4-squaryl diamides were obtained when the reaction of squaric acid was carried out with two equivalents of alkyl isocyanides under the same conditions. Asymmetric 2,4-squaryl diamides were obtained by reaction of squaramic acids with one equivalent of alkyl isocyanides.

Reactions of a Cationic Geminal Zr+/P Pair with Small Molecules

The metallocene cation complex [Cp*2ZrCH3](+)[B(C6F5)4](-) inserts the phosphino-substituted alkyne Ph-C≡C-PPh2 into the [Zr]-CH3 bond to form the internally phosphane-stabilized cation [Cp*2Zr-C(═CMePh)PPh2](+) (10). Complex 10 adds alkyl isocyanides as well as pivalonitrile at a lateral site at the bent metallocene wedge with retention of the Zr-P bond. Complex 10 acts as a reactive frustrated Lewis pair toward heterocumulenes, undergoing Zr(+)/P addition reactions to the carbonyl groups of an alkyl isocyanate and of carbon dioxide to form the respective five-membered metallaheterocyclic adducts 13 and 14. With mesityl azide complex 10 undergoes a Zr(+)/P FLP N,N-addition reaction at the terminal azide nitrogen atom to form the four-membered FLP cycloadduct 15. The Zr(+)/P FLP is a reactive hydrogen activator. In a stoichiometric reaction it generates a hydridozirconocene cation that subsequently serves as a hydrogenation catalyst for various olefinic or acetylenic substrates. The Zr(+)/P pair 10 undergoes selective 1,4-addition reactions to conjugated enones and to a conjugated ynone to give the corresponding seven-membered metallacyclic Zr(+)/P FLP addition products. Many compounds of this study were characterized by X-ray diffraction.

Functionalized Cyclic Disilenes via Ring Expansion of Cyclotrisilenes with Isocyanides

The reaction of cyclotrisilenes 1 with 1 equiv of alkyl and aryl isocyanides at 25 °C affords the four-membered trisilacyclobutenes 2 with an exocyclic imine functionality as the major products of formal insertion into one of the Si–Si single bonds of 1. Minor quantities of the iminotrisilabicyclo[1.1.0]butanes 3 are obtained as side products, formally resulting from [1 + 2] cycloaddition of the isocyanides to the Si–Si double bond of 1. The bicyclo[1.1.0]butanes 3 become dominant at lower temperatures and may react with an additional 1 equiv of isonitriles to give the diiminotrisilabicyclo[1.1.1]pentanes 4.

A general synthesis of phosphaalkenes at zirconium with liberation of phosphaformamides

A general, atom-economical method for the synthesis of phosphaalkenes is reported via the net coupling of primary alkyl or aryl phosphines with aryl or alkyl isocyanides at zirconium. The phosphorus-containing ligand can be liberated as the phosphaformamide from zirconium by reaction with an organic electrophile.