A new cross-cycloaddition reaction between a wide range of isocyanides and 2-isocyanochalcones (or analogues) was developed for the expeditious synthesis of pyrrolo[3,4-b]indoles under thermal conditions. On the basis of the experimental results and DFT calculations, a mechanism for this domino reaction is proposed involving chemoselective heterodimerization of two different isocyanides to form 1,4-diazabutatriene intermediates, followed by an intramolecular [3+2]-cycloaddition and 1,3-proton shift.

A new cross-cycloaddition reaction between a wide range of isocyanides and 2-isocyanochalcones (or analogues) was developed for the expeditious synthesis of pyrrolo[3,4-b]indoles under thermal conditions. On the basis of the experimental results and DFT calculations, a mechanism for this domino reaction is proposed involving chemoselective heterodimerization of two different isocyanides to form 1,4-diazabutatriene intermediates, followed by an intramolecular [3+2]-cycloaddition and 1,3-proton shift.

For the first time α-diazocarbonyls have been used as highly active N-terminal electrophiles in the presence of bicyclic amidine catalysts. The CN bond-forming reactions of active methylene compounds as C nucleophiles with α-diazocarbonyls as N-terminal electrophiles proceed quickly under ambient conditions, in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), because of the formation of the reactive N-terminal electrophilic intermediates. DBU activates both the active methylene and α-diazocarbonyl. Importantly, this reaction is general for both active methylenes and α-diazocarbonyls, and the activation mode will lead to new synthetic applications of α-diazocarbonyls.

For the first time α-diazocarbonyls have been used as highly active N-terminal electrophiles in the presence of bicyclic amidine catalysts. The CN bond-forming reactions of active methylene compounds as C nucleophiles with α-diazocarbonyls as N-terminal electrophiles proceed quickly under ambient conditions, in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), because of the formation of the reactive N-terminal electrophilic intermediates. DBU activates both the active methylene and α-diazocarbonyl. Importantly, this reaction is general for both active methylenes and α-diazocarbonyls, and the activation mode will lead to new synthetic applications of α-diazocarbonyls.

The insertion of an aryne into a CS bond can suppress the addition of an S nucleophile to the aryne in the presence of palladium. Catalyzed by Pd(OAc)₂, a wide range of α-carbamoyl ketene dithioacetals readily react with arynes to selectively afford functionalized 2-quinolinones in high yields under neutral reaction conditions by a CS activation/aryne insertion/intramolecular coupling sequence. The attractive feature of the new strategy also lies in the versatile transformations of the alkythio-substituted quinolinone products.

On the terminal diazo nitrogen atom, two CN bonds are formed in the bicyclization reaction of the readily available acyclic substrates with diazomethanes as 1,3-dipoles. The tandem 1,3-dipolar cycloaddition/intramolecular aza-addition/oxidative aromatization reaction can tolerate a variety of functional groups and proceeds under mild metal-free conditions to give substituted analogues of withasomnine alkaloids in good to high yields in a single step.

A new [3+2] cycloaddition strategy for the direct synthesis of highly substituted pyrroles from the readily available α-acylketene dithioacetals (or related substrates) and commercially available propargylamines under mild metal-free conditions has been developed. In this reaction, the acyl group plays a critical role in driving the conjugate addition of propargylamine and further cyclization to give pyrroles. Furthermore, the wide scope was confirmed by the preparation of 1,2,3,4-tetrasubstituted pyrroles (60–70% yields) via a formal 1,2-acyl migrating [3+2] cycloaddition pathway with N-methylprop-2-yn-1-amine as the secondary amine component.

Reactions directly involving triplet oxygen are an important issue in organic and biological chemistry. We now report that exposure of tetramic acids in the open air (molecular oxygen) at room temperature can lead to the formation of succinimide derivatives in high to excellent yields via tandem oxidation/1,2-benzyl migration. In this reaction, the dithiolane moiety plays a crucial role and succinimides are produced either in the presence or absence of dibutyl sulfide as reductant.

Substituents create access to molecular diversity. Under basic conditions, 6-azabicyclo[3.2.1]oct-6-en-2-ones 3 and pyrrolizidines 4 are efficiently synthesized, respectively, in a single step from ethyl isocyanoacetate 2 and divinyl ketones 1 bearing an aryl or alkyl group at the 2-position. For comparison, only the corresponding pyrrolizidines 4′ can be obtained from divinyl ketones 1′ bearing a methoxycarbonyl group at the 2-position.

A novel catalytic alkylation of indoles with allylic alcohols has been developed. Catalyzed by sulfuric acid (10 mol-%), the reaction between indoles 2 and allylic alcohols 1 based on ketene dithioacetal affords polyfunctionalized indoles 3 in good to excellent yields with high regioselectivities under mild conditions. The catalytic carbon–carbon coupling reaction provides a facile method for the environmentally benign functionalization of indoles with the advantages of good regiochemistry, atom efficiency, easily available catalyst, good yields and the synthetic potential of the polyfunctionalized indole products. Thus, further transformation of the resulting indoles 3 into pyridoindolone derivatives 4 was investigated. The efficiency of this carbon–carbon coupling reaction of 1 with 2 under the catalysis of sulfuric acid is due to the efficient formation of the reactive intermediate I, which is a carbocation that is strongly stabilized by two alkylthio groups at the terminal of the carbon–carbon double bond. The extension of this catalytic strategy to the synthesis of β-naphthols 5 was also achieved.

The synthesis of polyfunctionalized 4H-chromenes 3 and dihydrocoumarins 4 has been developed from the same substrates. Catalyzed by copper(II) bromide (0.3 equiv.), the reactions of the easily available ketene dithioacetals 1 with 2-(hydroxymethyl)phenols 2 lead to 4H-chromenes 3 in high to excellent yields in dichloromethane solvent, whereas, 3,4-trans-disubstituted dihydrocoumarins 4 are obtained in high yields with high diastereoselectivities by prolonging the reaction time or changing the solvent from dichloromethane to acetonitrile.

Hydrobromic acid was found to be a unique catalyst in CC bond-forming reactions with ketene dithioacetals. Distinctly different from other acids (including Lewis and Brønsted acids), the remarkable catalytic performance of hydrobromic acid in catalytic amounts was observed in the “acid”-catalyzed reactions of readily available functionalized ketene dithioacetals 1 with various electrophiles. Under the catalysis of 0.1 equivalents of hydrobromic acid, the reaction of 1 with carbonyl compounds 2 a–l gave polyfunctionalized penta-1,4-dienes 3 or conjugated dienes 4 in good to excellent yields. The reaction tolerated a broad range of substituents on both the ketene dithioacetals 1 and the carbonyl compounds 2. Application of this efficient CC bond-forming method generated coumarins 5 and benzofurans 7 under mild, metal-free conditions by hydrobromic acid-catalyzed reactions of 1 with salicylaldehydes 2 m–o and p-quinones 6 a–d, respectively. A new reactive species, a sulfur-stabilized carbonium ylide, formed depending on the nature of the counterion, and this was proposed as the key intermediate in the unique catalysis of hydrobromic acid.