We report herein the synthesis, structure, and molecular recognition of S₆- and (SO₂)₆-corona[6](het)arenes, and demonstrate a unique and efficient strategy of regulating macrocyclic conformation and properties by adjusting the oxidation state of the heteroatom linkages. The one-pot nucleophilic aromatic substitution reaction of 1,4-benzenedithiol derivatives, biphenyl-4,4′-dithiol and 9,9-dipropyl-9H-fluorene-2,7-dithiol with 3,6-dichlorotetrazine afforded S₆-corona[3]arene[3]tetrazines. These compounds underwent inverse-electron-demand Diels–Alder reaction with enamines and norbornadiene to produce S₆-corona[3]arene[3]pyridazines. Facile oxidation of sulfide linkages yielded (SO₂)₆-corona[3]arene[3]pyridazines. All corona[6](het)arenes adopted generally hexagonal macrocyclic ring structures; however, their electronic properties and conformation could be fine-tuned by altering the oxidation state of the sulfur linkages. Whereas (SO₂)₆-corona[3]arene[3]pyridazines were electron-deficient, S₆-corona[3]arene[3]pyridazines acted as electron-rich macrocyclic hosts that recognized various organic cations in both aqueous and organic solutions.

Reported is a new and efficient strategy for rapid construction of the chiral tetrahydropyrrolo[2,1-a]isoquinolin-3(2H)-one structure from unique tertiary enamide synthons. A Cu(OTf)₂/chiral Pybox complex catalyzes the intramolecular enantioselective addition of tertiary enamides to ketonic carbonyls with subsequent diastereoselective interception of the resulting acyliminium by tethered electron-rich aryl moiety. The tandem reaction produces diverse tetrahydropyrrolo[2,1-a]isoquinolin-3(2H)-one derivatives as the sole diastereoisomers in good to excellent yields with up to 98.5 % ee. The transformations of the resulting heterocycles into various hexahydropyrrolo[2,1-a]isoquinoline derivatives were also demonstrated. The cyclization products, which are difficult to obtain by other synthetic means, are structural motifs found in many bioactive alkaloids.

Reported is a new and efficient strategy for rapid construction of the chiral tetrahydropyrrolo[2,1-a]isoquinolin-3(2H)-one structure from unique tertiary enamide synthons. A Cu(OTf)₂/chiral Pybox complex catalyzes the intramolecular enantioselective addition of tertiary enamides to ketonic carbonyls with subsequent diastereoselective interception of the resulting acyliminium by tethered electron-rich aryl moiety. The tandem reaction produces diverse tetrahydropyrrolo[2,1-a]isoquinolin-3(2H)-one derivatives as the sole diastereoisomers in good to excellent yields with up to 98.5 % ee. The transformations of the resulting heterocycles into various hexahydropyrrolo[2,1-a]isoquinoline derivatives were also demonstrated. The cyclization products, which are difficult to obtain by other synthetic means, are structural motifs found in many bioactive alkaloids.

Catalyzed by Rhodococcus erythropolis AJ270, a nitrile hydratase–amidase containing microbial whole-cell catalyst under mild conditions, enantioselective desymmetrizations of meso-cyclopentane-1,3-dicarbonitriles and cyclopentane-1,3-dicarboxamides were studied. Although the nitrile hydratase was found to exhibit high enzymatic activity, but low 1R enantioselectivity toward dinitriles, a number of 2,2-unsymmetrically substituted meso-cyclopentane-1,3-dicarboxamide substrates were converted by the 1S enantioselective amidase into quaternary carbon-bearing enantiopure (1S,2R,3R)-3-carbamoylcyclopentanecarboxylic acids in yields up to 94 %. The application of the method was demonstrated by convenient and practical transformations of the resulting (1S,2R,3R)-2-allyl-3-carbamoylcyclopentanecarboxylic acid derivatives into functionalized cyclopentane-fused δ-lactam and δ-lactone compounds.

We report the efficient and scalable synthesis and molecular-recognition properties of novel and water-soluble S₆-corona[3]arene[3]pyridazines. The synthesis comprises a one-pot nucleophilic aromatic substitution reaction between diesters of 2,5-dimercaptoterephthalate and 3,6-dichlorotetrazine followed by the inverse electron-demand Diels–Alder reaction of the tetrazine moieties with an enamine and exhaustive saponification of esters. The resulting S₆-corona[3]arene[3]pyridazines, which adopt a 1,3,5-alternate conformation in the crystalline state, are able to selectively form stable 1:1 complexes with dicationic guest species in water with association constants ranging from (1.10±0.06)×10³ M⁻¹ to (1.18±0.06)×10⁵ M⁻¹. The easy availability, large cavity size, strong and selective binding power render the water-soluble S₆-corona[3]arene[3]pyridazines useful macrocyclic hosts in various disciplines of supramolecular chemistry.

We report the efficient and scalable synthesis and molecular-recognition properties of novel and water-soluble S₆-corona[3]arene[3]pyridazines. The synthesis comprises a one-pot nucleophilic aromatic substitution reaction between diesters of 2,5-dimercaptoterephthalate and 3,6-dichlorotetrazine followed by the inverse electron-demand Diels–Alder reaction of the tetrazine moieties with an enamine and exhaustive saponification of esters. The resulting S₆-corona[3]arene[3]pyridazines, which adopt a 1,3,5-alternate conformation in the crystalline state, are able to selectively form stable 1:1 complexes with dicationic guest species in water with association constants ranging from (1.10±0.06)×10³ M⁻¹ to (1.18±0.06)×10⁵ M⁻¹. The easy availability, large cavity size, strong and selective binding power render the water-soluble S₆-corona[3]arene[3]pyridazines useful macrocyclic hosts in various disciplines of supramolecular chemistry.

By a one-pot reaction strategy and a stepwise fragment-coupling approach, three types of giant cage molecules with a triangular prism shape and an approximate cavity volume of 930 ų were synthesized. Through efficient aromatic nucleophilic substitution reactions of chlorotriazine with functionalized amines or aliphatic substitution reactions of the linking imino moieties with allyl bromide, the giant cages were successfully functionalized on the surface with multiple hydroxy, 2-pyridyl, or allyl groups. As evidenced by variable-temperature ¹H NMR spectroscopy, the D_3h- and C_3v-symmetric cage molecules underwent very slow conformational changes or deformation in solution because of their giant size and their flexible building units. Their giant cavities, different electronic interiors, and facile multiple exterior surface functionalization could render the molecular cages powerful three-dimensional macrocyclic hosts that might find wide applications in supramolecular science.

A number of azacalix[2]pyrimidine[2]triazines were synthesized in moderate to good yields from both a step-wise fragment coupling approach and a one-pot reaction strategy starting from 4,6-diaminopyrimidines and cyanuric chloride. Nucleophilic aromatic substitution reaction of resulting dichloro-substituted azacalix[2]pyrimidine[2]triazines with NH₄Cl led to the formation of NH₂-bearing azacalix[2]pyrimidine[2]triazine analogs. Azacalix[2]pyrimidine[2]triazines adopted symmetric 1,3-alternate conformations in solution while twisted 1,3-alternate conformations were observed in the solid state. In the presence of different additives during the growth of single crystals, azacalix[2]pyrimidine[2]triazines containing amino (-NH₂) groups gave varied self-assembled structures due to the formation of different intermolecular hydrogen bond motifs.

O₆-Corona[3]arene[3]tetraazines, a new class of macrocyclic compounds, were synthesized efficiently in a one-pot reaction from the nucleophilic aromatic substitution reaction between 1,4-dihydroxybenzene derivatives and 3,6-dichlorotetrazine in warm acetonitrile. In the crystalline structure, the resulting macrocycles adopt highly symmetric structures of a regular hexagonal cavity with all bridging oxygen atoms and tetrazine rings located on the same plane with phenylene units orthogonally orientated. The constitutional aromatic rings are able to rotate around the macrocyclic annulus, depending on the steric effect of the substituents and temperature, in solution. The electron-deficient nature revealed by cyclic voltammetry, differential pulse voltammetry, and characteristic absorbances at a visible region show the O₆-corona[3]arene[3]tetrazines to be suitable macrocyclic receptors for electron-rich guests.

O₆-Corona[3]arene[3]tetraazines, a new class of macrocyclic compounds, were synthesized efficiently in a one-pot reaction from the nucleophilic aromatic substitution reaction between 1,4-dihydroxybenzene derivatives and 3,6-dichlorotetrazine in warm acetonitrile. In the crystalline structure, the resulting macrocycles adopt highly symmetric structures of a regular hexagonal cavity with all bridging oxygen atoms and tetrazine rings located on the same plane with phenylene units orthogonally orientated. The constitutional aromatic rings are able to rotate around the macrocyclic annulus, depending on the steric effect of the substituents and temperature, in solution. The electron-deficient nature revealed by cyclic voltammetry, differential pulse voltammetry, and characteristic absorbances at a visible region show the O₆-corona[3]arene[3]tetrazines to be suitable macrocyclic receptors for electron-rich guests.

We herein report the synthesis and metal-directed coordination self-assembly behaviors of three new macrocyclic azacalix[4]aromatics that comprise various numbers of pyridine and pyrazine rings bridged by N-CH₃ groups. Structural characterization of 1–3 explored that their conformations are fluxional in solution and each adopts a 1,3-alternate configuration in crystalline solids. The macrocyclic skeletons in azacalixaromatic 1–3 afford a good platform to designedly arrange coordination sites in a unique way relative to conventional multidentate ligands. Solid-state structures of three coordination self-assembled silver complexes (13–15) of 1–3 determined by X-ray crystallography suggest that the nitrogen atoms on procumbent aromatics have better coordination ability than those on perpendicular aromatics and dictate the whole coordination self-assemblies. Unique discrete and 1D chain-like structures were thus obtained. This system may afford a deeper insight into the coordination self-assembly studies of heteroatom-bridged calixaromatics, possibly extending potential application of this novel macrocyclic polydentate organic compounds in the synthesis of functional metal organic framework formation.

Tandem reactions for the efficient synthesis of multifunctionalized 1,2,3,4-tetrahydropyridines, 2,3-dihydropyridin-4(1H)-ones, and pyridine derivatives have been developed and reaction mechanisms have been investigated. Synthetic cascades are initiated by the Zn(OTf)₂-mediated [5+1] cycloaddition of N-formylmethyl-substituted tertiary enamides to isocyanides, thus leading to the versatile heterocyclic enamino imine intermediates. Interception of the intermediates by diastereoselective reduction of imine functionality with Me₄NBH(OAc)₃ afforded 1,6-disubstituted trans-3-hydroxy-4-arylamino- or -alkylamino-1,2,3,4-tetrahydropyridines, whereas acylation of the imino group followed by acidic hydrolysis produced 1,6-disubstituted 3-acyloxy-2,3-dihydropyridin-4(1H)-ones. Aerobic oxidation led to the aromatization followed by intermolecular acyl-group transfer from the pyridinium nitrogen to the 3-hydroxy moiety, thereby yielding substituted 3-acyloxy-4-aminopyridines. Synthetic potentials of the resulting products have been demonstrated by expedient and highly stereoselective synthesis of cis,cis-4,5-dihydroxy-2-phenylpiperidine and trans,trans-4-amino-5-hydroxy-2-phenylpiperidine compounds, which are important in medicinal chemistry, through simple and practical reduction reactions.