A transition-metal-free process for the synthesis of unsymmetrical aryl sulfides via dual C–S bond formation by a one-pot three-component reaction of alcohols, organohalides, and odorless sodium thiosulfate in water has been developed. In addition, the aryl sulfides could also be prepared by the reaction of the corresponding alcohols and Bunte salts under the identical conditions. This protocol provides a green and efficient manner for the construction of various unsymmetrical aryl sulfides.

A new and facile approach toward highly functionalized carbamimidoseleknoates was developed through the copper(I)-catalyzed ligand-promoted four-component reaction of isocyanides, selenium, amines, and aryl iodides. The reaction constructed a range of organoselenium compounds containing an isoselenourea skeleton with potential bioactivity directly from selenium powder. The simplicity of method and broad diversity of substrates also highlight this work.

A Co(II)-catalyzed synthesis of sulfonyl guanidines by using amines, isonitriles, and organic azides as nitrene sources has been developed. This protocol provides an environmentally friendly and simple strategy for the synthesis of sulfonyl guanidine derivatives by employing a range of substrates and will find potential applications in organic synthesis. The computational and EPR studies suggested the formation of guanidine derivatives via a cobalt–nitrene radical intermediate.Keywords: amines; cobalt(II)-catalysis; computational study; isonitriles; nitrene; organic azides; sulfonyl guanidines;

A Co(II)-catalyzed isocyanide insertion reaction with sulfonyl azides in alcohols to form sulfonyl isoureas via nitrene intermediate has been developed. This protocol provides a new, environmentally friendly, and simple strategy for the synthesis of sulfonyl isourea derivatives by employing a range of substrates under mild conditions.

A novel silver-catalyzed fluorination reaction of carbonyl directed alkynes in the presence of N-fluorobenzenesulfonimide and water with high regioselectivities has been developed. The established protocol provides an alternative method for rapid assembly of α-fluoroketone derivatives under simple and mild reaction conditions. The reaction pathway involves a ring closure and opening process for the construction of new C–O and C–F bonds. In addition, a fluorine-containing indanone was observed through further N-heterocyclic carbene catalyzed intramolecular crossed-benzoin reaction of α-fluoroketone.

A cobalt-catalyzed [4 + 1] cycloaddition of easily accessible amides with isocyanides for the efficient synthesis of 3-iminoisoindolinone derivatives in high yield under mild conditions via intramolecular C(sp2)–H activation and isocyanide insertion is reported. The annulation was found to be applicable to a broad range of substrates, including arylamides, heteroarylamides, and acrylamide derivatives. Strongly coordinating N-heterocyclic directing groups such as pyridine, pyrimidine, and even pyrazole were fully tolerated in this cobalt-catalyzed C–H activation reaction.

A novel and facile metal-free method for the green synthesis of 1,2,4-selenadiazol-5-amine derivatives through the aerobic radical-cascade multi-component reactions of isocyanides, selenium powder and imidamides is reported herein. O2 in the air was employed as the green oxidant to achieve the cycloaddition with the generation of H2O as the sole by-product. It also features good functional group compatibility and broad substrate scope. In addition, this method was successfully applied to the functionalization of biologically active molecules.

A chemoselective Co(II)-catalyzed effective synthesis of sulfonylamidyl amide and 3-imine indole derivatives by using isocyanides and sulfonyl azides has been developed. This protocol provides a new, environmentally friendly and simple strategy for the efficient synthesis of the sulfonylamidyl amide and 3-imine indole derivatives with a wide range of substrates in the absence of any oxidants and additives.

An efficient silver-catalyzed domino cycloisomerization reaction for regioselective assembly of 1H-isochromene derivatives from o-alkynylaryl aldehydes with enaminones as the external nuclephiles is developed. This protocol affords isochromene derivatives in moderate to good yields under simple and mild reaction conditions.Download high-res image (100KB)Download full-size image

An efficient and practical synthesis of benzothiazine by K2S initiated sulfur insertion reaction with enaminones via electron catalysis is developed. This protocol provides a new, environment-friendly and simple strategy to construct benzothiazine derivatives via formation of two C–S bonds under transition metal-free, additive-free and oxidant-free conditions. K2S not only provides the sulfur insertion source, but also ignites the reaction through the formation of a trisulfur radical anion and electrons in DMF.

Palladium-catalyzed intramolecular Heck reaction and aminopalladation of N-(2-(1-phenylvinyl)phenyl)aniline for the efficient synthesis of dihydroindeno[1,2,3-kl]acridines and 3-arylindoles via tuning of the phosphine ligands and solvents under two optimized conditions are reported. The reaction follows a 1,4-Pd migration, aminopalladation, C(sp2)–H activation, as well as five- and six-membered-ring fusion to form different products. The dihydroindeno[1,2,3-kl]acridine derivatives showed higher triplet energy (ET) levels than common blue phosphorescent dopant and may serve as good host candidates for blue triplet emitters.

A palladium-catalyzed cascade arene/alkyne annulation reaction for the synthesis of fluorene-benzoxazine derivatives is developed. This transformation involves a 6-exo-dig cyclization, a 1,3-oxazine vinylpalladium intermediate, and a C–H bond activation.

A series of 2-aminoquinolines were afforded by Co(acac)2 catalyzed isocyanide insertion with 2-vinylanilines under an O2 atmosphere. This reaction not only uses low toxicity Co(acac)2 as the catalyst and oxygen as the oxidant, but also allows the construction of new C(sp2)–C(sp2) and C(sp2)–N bonds in a single-step.

An I2/CHP-mediated cross-coupling reaction of isocyanides with readily accessible amines via C–N formation is described for carbodiimide synthesis in moderate to excellent yields. This represents a metal-free strategy for a coupling reaction of isocyanides with amines, and it provides an efficient approach for symmetric and unsymmetric functionalized carbodiimide derivative synthesis under mild conditions.

A novel synthetic approach toward 1,4-disubstituted 1,2,3-triazoles and 1,5-disubstituted 1,2,3-triazoles by aerobic oxidative cycloaddition of α-chlorotosylhydrazone with primary aryl amine has been developed. Significantly, the reaction proceeds smoothly to afford 1,4-disubstituted 1,2,3-triazoles and 1,5-disubstituted 1,2,3-triazoles under catalyst-free, metal-free, azide-free, and peroxide-free conditions.

A Pd-catalyzed highly regioselective 6-exo-dig cyclization/alkenylation reaction of ortho-ethynylanilides has been developed. This tandem cross-coupling protocol represents a simple, efficient, step- and atom-economic approach for the construction of scarcely known polyene-substituted benzo[d][1,3]oxazines in moderate to excellent yields with a broad substrate scope.

A series of interesting 7-hydroxy-2-aryl-6,7-dihydro-indol-4(5H)-ones 3 was successfully synthesized in moderate to good yields by the domino reactions of different arylglyoxals 1 with enamines 2 under catalyst-free conditions. 7-Hydroxy-2-aryl-6,7-dihydro-indol-4(5H)-ones 3 could also be prepared in moderate yields by the iodine-promoted one pot-two step reactions of methyl ketones 6 with enamines 2. The reaction of 3a with N-methyl indole 7a in the presence of PTSA afforded 2′-aryl-6′,7′-dihydro-[3,7′-biindol]-4′(5′H)-ones 8a in 81% yield. In addition, 3,7′-bis-indoles 8 could also be observed in 47–73% yields by one pot domino reaction of arylglyoxals 1 with enamines 2 and indoles 7 over two steps. This protocol provides a simple and practical method to construct diverse 7-hydroxy-6,7-dihydro-indole derivatives 3 and 3,7′-bis-indoles 8 from easily obtained starting materials.

A new practical synthesis of phthalimides through 1,3-dipolar cycloaddition of CO2 with isocyanides and in situ generated aryne is reported here. A series of phthalimide derivatives are observed in moderate to good yields under mild conditions.

A palladium-catalyzed efficient C–H acylation reaction of biaryl-2-amines and aromatic aldehydes is developed. This dehydrogenative cross-coupling protocol could furnish monoacylation and diacylation products in moderate to good yields with a broad substrate scope and good regioselectivity.

A series of air-stable aminocarbene-like palladium(II) complexes were easily prepared by the reaction of bis-aromaticisocyanide-dichloropalladium(II) with N-arylbenzamidines. 0.1 mol % of the optimal palladium complex 3a showed excellent catalytic activity for Suzuki–Miyaura cross-coupling reaction at room temperature and the desired products were isolated in up to 98% yields. Moreover, a large-scale reaction showed that 0.01 mol % 3a was enough to catalyze the coupling reaction efficiently at room temperature to give the desired product in 93% yield.

A method for palladium-catalyzed cascade reactions of isocyanides with enaminones has been developed. This methodology provides a direct approach to 4-aminoquinoline derivatives under mild conditions with up to 98% yields.Keywords: amino quinoline; cascade reaction; isocyanide; palladium

An efficient method for the construction of 6-alkyl phenanthridines by tert-butyl peroxybenzoate (TBPB)-mediated 2-isocyanobiaryl insertion with 1,4-dioxane was established. Two new C–C bonds were formed in this reaction via a sequential C(sp3)–H/C(sp2)–H bond functionalization under metal-free conditions.

An I2/TBHP mediated oxidation of commercially available indoles has been developed, which affords isatins in moderate to good yields.

A novel and efficient protocol for the creation of 6-amino phenanthridine derivatives by Co(acac)2-catalyzed isocyanide insertion with 2-aryl anilines under an O2 atmosphere via homolytic aromatic substitution (HAS) type C–H functionalization has been developed. This reaction not only proceeds smoothly utilizing O2 as the oxidant but also provides a new approach to construct phenanthridine derivatives utilizing readily available 2-aryl anilines with isocyanides instead of 2-isocyanobiaryls with different radical precursors.

An efficient I2 (20 mol %)/TBPB mediated oxidative formal [4 + 1] cycloaddition of N-tosylhydrazones with anilines via C–N/N–N bond formation and S–N cleavage has been developed. This protocol represents a simple, general, and efficient approach for the construction of 1,2,3-triazoles under metal-free and azide-free conditions by utilizing a catalytic amount of I2.

Mn(III)-mediated reactions of 2-isocyanobiaryls with 1,3-dicarbonyl compounds were described for the construction of 6-alkylated and 6-monofluoro-alkylated phenanthridines in moderate to good yields. The reaction involves formation of two new C–C bonds and one C–C bond cleavage.

An efficient and practical synthetic approach to access to 2H-pyrrolo[3,4-c]quinolin-4(5H)-one/2H-pyrrolo[3,4-c]quinoline derivatives by the reaction of 2-aminoarylacrylates/2-aminochalcones and tosylmethyl isocyanide (TosMIC) via a one pot van Leusen reaction and cyclization under basic conditions has been reported. The desired products could be obtained in moderate to good yields.

The chemoselective alkylation of tryptamine derivatives with 2-oxo-1-pyrrolidine compounds, catalyzed by In(OTf)3, was investigated. A series of 2-alkyl and N-alkyl tryptamine derivatives were synthesized under mild conditions with good total yields (up to 99%) and chemoselectivity (up to 95:5).

Chemoselective 2-isocyanoethylindole-based domino reactions for the construction of polycyclic spiroindoline derivatives and polysubstituted pyrroles have been developed. The reaction of 2-isocyanoethylindoles and gem-diactivated olefins lead to the polycyclic spiroindoline derivatives (up to 92% yields) in EtOH under reflux conditions. Furthermore, the three-component reaction of 2-isocyanoethylindoles with gem-diactivated olefins and secondary amines afford polysubstituted pyrroles (in moderate yields) in CH3CN under reflux conditions.

A simple and practical method for the synthesis of spirodihydrocarboline derivatives from indolyl alcohol derivatives with enaminones via an iodine-catalyzed cascade formal [3 + 3] cycloaddition reaction has been developed. The reaction afforded the desired products under mild conditions in moderate to good yields with excellent regioselectivities.Keywords: carbolines; cascade reaction; formal [3 + 3] cycloaddition reaction; indolyl alcohol; iodine

The first investigation into two CO bonds of CO2 reacting in one reaction through dual 1,3-dipolar cycloaddition of CO2 with isocyanides and dialkyl acetylenedicarboxylates has been reported. The reaction proceeded efficiently at 80 °C at a pressure of 1 atm of CO2, affording symmetric 1,6-dioxospiro[4,4]nonane-3,8-diene derivatives in moderate yields.

A novel catalyst-free one-pot tandem reaction for the stereoselective construction of polycyclic spiroindolines was developed. This method offers a straightforward access to structurally diverse polycyclic spiroindoline derivatives in high yields (up to 90%) with excellent levels of diastereoselectivity.

A multicomponent domino reaction for the chemoselective, catalyst-free synthesis of polysubstituted pyrroles from readily available isocyanides, primary or secondary amines, and gem-diactivated olefins has been developed. Structurally diverse pyrroles were obtained in moderate to good yields under mild conditions.

A novel I2/TBHP-mediated direct oxidative diamination reaction of indoles with anilines was developed. The reaction proceeded smoothly under aqueous and open air reaction conditions. This protocol provides a practical synthetic method for the synthesis of Tryptanthrin and the construction of N–C3 linked pyrrolidinoindolines which is the core structure of Psychotrimine.

An efficient sodium hydrogen sulfate catalyzed alkylation of indoles or amines with tertiary enamides has been accomplished in water, affording the pharmacologically and biologically active 2-oxo-1-pyrrolidine derivatives in moderate to excellent yields. The key to our success is the use of NaHSO4 as a low loading, inexpensive, green and recyclable catalyst and the reactions could be scaled up to gram level.

A diastereoselective synthesis of 2-methyl-4-amino-1,2,3,4-tetrahydro-quinoline derivatives was achieved through the reaction of aromatic amines and tert-enamides in water under reflux conditions. The desired products could be obtained in moderate to excellent yields utilizing water as solvent without any catalyst or additive.

I2-promoted domino reactions of isatins or 3-hydroxyindolin-2-one derivatives with enaminones under O2 conditions have been established. The reactions of isatins with enaminones afforded functionalized tetracyclic pyrrolo[2,3,4-kl]acridine derivatives in moderate to good yields through domino cyclization and C–H oxidation. The reactions of 3-hydroxyindolin-2-one derivatives with enaminones proceeded well to give functionalized pyrrolo[2,3,4-kl]acridine derivatives via tandem ring-opening/recyclization/methyl migration sequences with two C–C bonds cleaved.

A novel CuI/BF3·Et2O/O2-mediated reaction utilizing ketones and benzylamines for the construction of substituted imidazoles in one step under mild conditions has been demonstrated. This protocol involved the removal of eight hydrogen atoms, the functionalization of four C(sp3)–H bonds and three new C–N bond formations.

Multicomponent reactions of acenaphthylene-1,2-dione with diaroylmethanes and electron-rich pyrazol-5-amines have been discovered. A series of new and polyfunctionalized pentacyclic pyrazole-fused naphtho[1,8-fg]isoquinolines were regioselectively synthesized. The reactions were easy to perform simply by mixing three common reactants in AcOH. During these reaction processes, the insertion of active methylene of diaroylmethane into the sp2–sp2 C–C bond of the cyclohexa-2,5-dienone ring was readily achieved and two C–C bonds were cleaved under transition-metal-free conditions.

A Pd-catalyzed highly regioselective 6-exo-dig cyclization/alkenylation reaction of ortho-ethynylanilides has been developed. This tandem cross-coupling protocol represents a simple, efficient, step- and atom-economic approach for the construction of scarcely known polyene-substituted benzo[d][1,3]oxazines in moderate to excellent yields with a broad substrate scope.

An efficient method for the construction of 6-alkyl phenanthridines by tert-butyl peroxybenzoate (TBPB)-mediated 2-isocyanobiaryl insertion with 1,4-dioxane was established. Two new C–C bonds were formed in this reaction via a sequential C(sp3)–H/C(sp2)–H bond functionalization under metal-free conditions.

The first investigation into two CO bonds of CO2 reacting in one reaction through dual 1,3-dipolar cycloaddition of CO2 with isocyanides and dialkyl acetylenedicarboxylates has been reported. The reaction proceeded efficiently at 80 °C at a pressure of 1 atm of CO2, affording symmetric 1,6-dioxospiro[4,4]nonane-3,8-diene derivatives in moderate yields.

An efficient and practical synthetic approach to access to 2H-pyrrolo[3,4-c]quinolin-4(5H)-one/2H-pyrrolo[3,4-c]quinoline derivatives by the reaction of 2-aminoarylacrylates/2-aminochalcones and tosylmethyl isocyanide (TosMIC) via a one pot van Leusen reaction and cyclization under basic conditions has been reported. The desired products could be obtained in moderate to good yields.

An efficient and practical synthesis of benzothiazine by K2S initiated sulfur insertion reaction with enaminones via electron catalysis is developed. This protocol provides a new, environment-friendly and simple strategy to construct benzothiazine derivatives via formation of two C–S bonds under transition metal-free, additive-free and oxidant-free conditions. K2S not only provides the sulfur insertion source, but also ignites the reaction through the formation of a trisulfur radical anion and electrons in DMF.

Mn(III)-mediated reactions of 2-isocyanobiaryls with 1,3-dicarbonyl compounds were described for the construction of 6-alkylated and 6-monofluoro-alkylated phenanthridines in moderate to good yields. The reaction involves formation of two new C–C bonds and one C–C bond cleavage.