Ligand-free palladium assisted insertion of isocyanides to urea derivatives for cascade synthesis of phenylamino-substituted quinazolinones

Palladium catalyzed cascade coupling of substituted urea derivatives and tert-butyl isocyanide for the efficient synthesis of phenylamino-substituted quinazolinones has been developed in moderate to good yields. This method provides a short and alternative approach for the synthesis of quinazolinones derivatives which are valuable compounds with biological and pharmacological potentials. A plausible mechanistic scheme is proposed.     

The rotational spectrum of propynyl isocyanide

Propynyl isocyanide, CH₃C₂NC, has been prepared by vacuum pyrolysis of pentacarbonyl-(1,2-dichloropropenyl isocyanide) chromium, (CO)₅Cr–CN–C(Cl)=C(Cl)CH₃, and its ground state millimeter and microwave spectrum has been observed for the first time. r_s structural parameters of this molecule with a C_3v symmetry could be obtained from the rotational constants of several isotopomers: r_(C1–C2)=1.456(2) Å, r_(C2–C3)=1.206(2) Å, r_(C3–N)= 1.316(2) Å, r_(N–C4)= 1.175(2) Å, r_(H–C1)= 1.090(1) Å, >HCC=110.7(4)°. The nitrogen quadrupole coupling constant has been determined to be 878(2) kHz and measurements of the Stark effect allowed to obtain an electric dipole moment of 4.19(3) Debye. The results fit well into a series of related compounds and are in good agreement with data from ab initio calculations.     

One-pot synthesis of oxazoles using isocyanide surrogates

We wish to present herein a simple one-pot synthesis of 2,5-disubstituted oxazoles, starting from benzyl halides and acyl chlorides. The in situ formation of isocyanides, followed by the addition of an acyl chloride in the presence of a base leads to the desired oxazoles in good yields.     

tert-Butyl isocyanide revisited as a convertible reagent in the Groebke-Blackburn reaction

tert-Butyl isocyanide can serve as the convertible reagent in Groebke-Blackburn multi-component reactions. The effective removal of the tert-butyl group from the resulting imidazo[1,2-a]azines and -azoles is achieved on a gram scale in two steps without chromatographic purification.     

Palladium-catalyzed cyclization of o-alkynyltrifluoroacetanilides followed by isocyanide insertion: synthesis of 2-substituted 1H-indole-3-carboxamides

A base-controlled synthesis of 2-substituted secondary and tertiary 1H-indole-3-carboxamides through PdCl(2)-catalyzed cyclization of o-alkynyltrifluoroacetanilides followed by isocyanide insertion has been developed. The reaction proceeds smoothly at ambient temperature using O(2) in air as the sole oxidant of the palladium catalyst.     

Migratory insertion of isocyanide into a ketenyl–tungsten bond as key step in cyclization reactions

Treatment of the side-on tungsten alkyne complex of ethinylethyl ether [Tp*W(CO)₂(η²-C,C′-HCCOCH₂CH₃)]⁺ {Tp* = hydridotris(3,4,5-trimethylpyrazolyl)borate} (2a) with n-Bu₄NI afforded the end-on ketenyl complex [Tp*W(CO)₂(κ¹-HCCO)] (4a). This formal 16 ve complex bearing the prototype of a ketenyl ligand is surprisingly stable and converts only under activation by UV light or heat to form a dinuclear complex [Tp*₂W₂(CO)₄(μ-CCH₂)] (6). The ketenyl ligand in complex 4a underwent a metal template controlled cyclization reaction upon addition of isocyanides. The oxametallacycles [Tp*W(CO)₂{κ²-C,O-C(NHXy)C(H)C(Nu)O}] {Nu = OMe (7), OEt (8), N(i-Pr)₂ (9), OH (10), O_1/2 (11)} were formed by coordination of Xy-NC (Xy = 2,6-dimethylphenyl) at 4a and subsequent migratory insertion (MI) into the W-ketenyl bond. The resulting intermediate is susceptible to addition reactions with protic nucleophiles. Compounds 2a-PF₆, 4a/b, and 7–11 were fully characterized including XRD analysis. The cyclization mechanism has been confirmed both experimentally and by DFT calculations. In cyclic voltammetry, complexes 7–9 are characterized by a reversible W(ii)/W(iii) redox process. The dinuclear complex 11 however shows two separated redox events. Based on cyclic voltammetry measurements with different conducting electrolytes and IR spectroelectrochemical (SEC) measurements the W(ii)/W(iii) mixed valent complex 11⁺ is assigned to class II in terms of the Robin-Day classification.

The prototype ketenyl ligand is bound end-on despite a formal 16 valence electron count at the metal. This situation opens a reaction pathway for a multicomponent cyclization centred on the migration of the ketenyl ligand.     

Ultrasound irradiation promoted catalyst-free construction of formamidine framework using isocyanide as building blocks

Reactions of isocyanides with 2-mercaptobenzothiazole and 2-mercaptobenzoxazole afforded a series of compounds containing formamidine framework in moderate to high yields. These organic transformations were performed under mild and catalyst-free conditions. In addition to promoting the reactions, the use of ultrasound irradiation also allowed the process to be carried out under air atmosphere. A possible reaction mechanism was proposed based on the experimental results.     

Silver-catalyzed 2-isocyanobiaryls insertion/cyclization with phosphine oxides: synthesis of 6-phosphorylated phenanthridines

A silver-catalyzed 2-isocyanobiaryls insertion/cyclization with phosphine oxides was described for the construction of the 6-phosphorylated phenanthridines through radical addition of in situ formed P-centered radical to 2-isocyanobiphenyls and homolytic aromatic substitution process. The reactions could proceed smoothly to give the desired 6-phosphorylated phenanthridines promoted by AgOAc (20 mol %) with PhI(OAc)₂ (3.0 equiv).     

Cobalt-catalyzed electrochemical CH/NH functionalization of N-(quinolin-8-yl)benzamide with isocyanides

An efficient synthesis of functionalized iminoisoindolinone derivatives has been achieved via a mild electrochemical oxidative CH/NH functionalization/intramolecular annulations with isocyanides in undivided cell equipped with a nickel cathode. In the presence of earth abundant cobalt catalyst, versatile iminoisoindolinone derivatives obtained in good yields and in a sustainable manner by using electricity as an oxidant in place of stoichiometric amount of silver and copper salts.     

Silver-catalyzed [3+2+1] annulation of aryl amidines with benzyl isocyanide

A silver-catalyzed [3+2+1] annulation of amidines with benzyl isocyanide toward 2,4-diaryl-1,3,5-triazines was developed. A variety of symmetrical and unsymmetrical products were obtained in moderate to good yields. This work also features an oxidant-free approach to 2,4-disubstituted triazines.     

Synthesis of benzannulated N-heterocyclic carbene ligands by a template synthesis from 2-nitrophenyl isocyanide

The reaction of 2-nitrophenyl isocyanide 2 with [M(CO)5(thf)] (M=Cr, Mo, W) yields the isocyanide complexes [M(CO)5(2)] (3: M=Cr; 4: M=Mo; 5: M=W). Complexes 3-5 react with elemental tin under reduction of the nitro function of the isocyanide ligand to give the complexes with the unstable 2-aminophenyl isocyanide ligand. The coordinated 2-aminophenyl isocyanide ligand in all three complexes reacts spontaneously under intramolecular nucleophilic attack of the primary amine at the isocyanide carbon atom to yield the complexes with the NH,NH-benzimidazol-2-ylidene ligand (6: M=Cr; 7: M=Mo; 8: M=W). An incomplete reduction of the nitro group in 3-5 is observed when hydrazine hydrate is used instead of tin. Here the formation of complexes with a coordinated 2-hydroxylamine-functionalized phenyl isocyanide [(CO)5M-CN-C6H(4-)-2-N(H)-OH] is postulated and this unstable ligand again undergoes intramolecular cyclization to give the NH,NOH-stabilized benzimidazol-2-ylidene complexes 9-11. The tungsten derivative 11 can be allylated stepwise by a deprotonation/alkylation sequence first at the OH and then at the NH position to yield the monoallylated and diallylated species 12 and 13. The molecular structures of 3-5 and 12-13 were established by X-ray crystallography.     

An unexpected, novel, three-component reaction between isoquinoline, an isocyanide and strong CH-acids in water

An unexpected three-component condensation reaction between an isocyanide, isoquinoline and a strong CH-acid efficiently provides 1,2-dihydroisoquinoline derivatives in a one-pot reaction in water at 70 °C without using any catalyst.     

Electronic communication between tungsten alkylidyne and metal isocyanide complex fragments across phenyleneethynylene bridges

Heteronuclear metal complexes of the type [X(CO)₂(LL)WC(-C₆H₄-CC)_p-C₆H₄-NC-]_nML_m (X = Cl, Br; LL = tmeda, dppe; p = 0-3; n = 1 for Cr(CO)₅, n = 2 for ReX(CO)₃, PdCl₂, PdI₂, and PtI₂) have been prepared. The molecular structure of one example, [Cl(CO)₂(tmeda)WC-C₆H₄-NC-]₂PdI₂, was determined by X-ray crystallography. The extent of electronic communication between the tungsten alkylidyne and the metal isocyanide centers was probed by various spectroscopic techniques. In the parent systems (p = 0), the electronic changes due to modification of the isocyanide metal complex fragments could be distinguished clearly by the ¹³C NMR chemical shift of the alkylidyne carbon atom and the d → π^∗ and π → π^∗ electronic transitions of the metal alkylidyne system. However, only residual effects could be discerned for the longer systems using these spectroscopic probes. Probes based on the emission property of the tungsten alkylidyne fragment proved to be the most useful in distinguishing long-range effects in those cases where the isocyanide metal complex fragment is capable of quenching the emission. This is the case for ML_m = PdCl₂ and PdI₂. Partial quenching effects were still observed at the longest investigated distance between the metal centers of about 3.1 nm. The available evidence suggests that the quenching mechanism is electron transfer.     

Synthesis of new alkoxy/alkylthiovinylated oxazoles using tosylmethyl isocyanide

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The final steps of the Oppolzer cyclization: mechanism of the insertion of alkenes into allylpalladium(II) complexes

We report here the results of a computational study on the the mechanism of the Oppolzer cyclization. These results lead us to conclude that the insertion of olefins in Pd-allyl complexes probably takes place directly from the eta(3)-allyl species. The presence of a phosphane ligand in the reagents plays the role of enhancing the electron density on the Pd atom; this makes the alkene moiety more reactive towards insertion by back-donation from the metal. The results also indicate that the configuration of the new stereogenic centers is fixed in the insertion of the alkene into the (eta(3)-allyl)palladium species.     

An isocyanide based multi-component reaction under catalyst- and solvent-free conditions for the synthesis of unsymmetrical thioureas

A new and efficient method for the synthesis of thiourea derivatives by a sequential one-pot, three-component reaction between aromatic isocyanides, amines, and 1,2-di-tert-butyldisulfane (DTBS) was developed and 27 different examples were synthesized in good to excellent yields. DTBS was identified as an effective sulfur surrogate without the use of both catalysts and solvents. This protocol does not employ any transition metal catalyst or special experimental setup.     

1-Methylimidazole-catalyzed reaction between tosylmethyl isocyanide and dialkyl acetylenedicarboxylates:An efficient synthesis of functionalized pyrroles

An efficient 1-methylimidazole-catalyzed synthesis of dialkyl 2-[(4-methylphenyl)sulfonyl]-1H-pyrrole-3,4-dicarboxylates is described.The reactive 1:1 zwitterionic intermediate formed by the addition of 1-methylimidazole to dialkyl acetylenedicarboxylates is trapped by tosylmethyl isocyanide(TOSMIC) to afford the title compounds in excellent yields.