Tandem Cyclization of -Hydroxyphenyl Propargyl Alcohols with Thionucleophiles: A Metal-Free and Modular Access to 3-Fluoroalkylsulfonyl/Thio Benzofurans.

Despite both fluoroalkylsulfonyl groups and benzofurans are important bioactive moieties, the construction of fluoroalkanesulfonylated benzofurans that incorporate these two fragments remains underdeveloped. Here, we report a tandem cyclization protocol to construct a wide range of 3-fluoroalkylsulfonyl benzofurans using readily accessible -hydroxyphenyl propargyl alcohols and sodium fluoroalkanesulfinates. Furthermore, this synthetic strategy can also be adapted to prepare 3-thio benzofurans by changing the S-nucleophiles to thiols or thiophenols.

EDA Complex-Promoted Cascade Cyclization of Alkynes Enabling the Rapid Assembly of 3-Sulfonylindoles and Vinyl Sulfone Oxindoles.

Herein, we disclose a photoinduced radical cascade cyclization of alkynes with sulfinates via a novel EDA complex for the synthesis of various 3-sulfonylindoles and vinyl sulfone oxindoles, which are crucial motifs in medicinal and biological chemistry. The reaction proceeds under mild, photocatalyst- and transition-metal-free conditions, featuring operational simplicity, broad substrate scope, and easy scalability. Mechanistic studies reveal that the reaction is initiated with a photoinduced intermolecular charge transfer from sulfinates to -sulfonamides, generating a sulfonyl radical followed by an -centered radical, thus enabling the cascade cyclization process.

Silver-catalyzed P-centered anion nucleophilic addition to isocyanide: access to 2-phosphinoyl indoles/indol-3-ols.

A silver-catalyzed chemoselective cascade nucleophilic addition of a P-centered anion to isocyanides and cyclization reaction was developed for the efficient and practical synthesis of a wide range of 2-phosphinoyl indole and indol-3-ol derivatives. Unlike the well-documented synthesis of phosphorus-functionalized heterocycles a P-centered radical, an anionic reactivity profile of phosphine oxides is most likely involved in this domino transformation.

De Novo Synthesis of 2,2'-Bipyridines and Related Bis-azines via Cascade Coupling and Double Pyridannulation of Isocyanides.

Herein, we present a new and general protocol for the assembly of 2,2'-bipyridyls from nonpyridine substrates without using any metal catalysts or organometallic reagents. The process starts from the coupling of two 1,3-dienyl isocyanides followed by a 6π-electrocyclization/aromatization cascade featuring the simultaneous formation of two pyridine rings in a single operation. Notably, this strategy is also applicable to the construction of nonsymmetrical 2-(2-pyridyl)-quinolines/-quinoxalines.

Access to 2-thio/selenoquinolines domino reaction of isocyanides with sulfur and selenium in water.

A domino reaction of -alkenylaryl isocyanides with elemental sulfur and selenium in pure water was developed for the efficient and green synthesis of quinoline-2-thione and diquinolyl diselenide derivatives. Mechanistical investigation reveals that intramolecular nucleophilic addition of an alkenyl group to the generated isothio/isoselenocyanate accounts for the formation of a quinoline-ring. Moreover, this transformation is also amendable for the convenient preparation of 2-fluoromethylthio-/seleno-quinolines by a one-pot three-component reaction.

Isocyanide Heterodimerization-Triggered Three-Component Reaction: Diversity-Oriented Synthesis of Quinoxalines.

Known isocyanide-based multicomponent reactions (IMCRs) are usually triggered by addition of the isocyano group to the strong electrophilic component. We herein report a new isocyanide-based three-component reaction, in which an unprecedented quinoxaline-based zwitterionic intermediate is generated from the chemoselective heterodimerization of weak electrophilic -diisocyanoarenes and common isocyanides. This reactive zwitterion could react with various trapping agents to furnish a range of structurally diverse quinoxalines.

Divergent Synthesis of Chromenoindoles and Spiroindolines via Domino Reaction of Indolyl-Substituted Isocyanides with Quinone Esters.

A dearomative spirocyclization of tryptamine-derived isocyanides with quinone esters is developed for the divergent synthesis of structurally complex chromeno[2,3-]indole and polycyclic spiroindoline scaffolds. This domino reaction features the formation and conversion of the six-membered dihydropyran ring with an amendable ,-aminal moiety.

Synthesis of Trisubstituted Chromanes by Lewis-Base-Catalyzed Three-Component Electrophilic Thiofunctionalization of Cyclopropene with Phenols via a Formal [3 + 3] Annulation.

A Lewis-base-catalyzed three-component electrophilic thiofunctionalization of cyclopropene with phenol is developed to furnish various trisubstituted chromanes in high -diasteroselectivity. This metal-free protocol is easy to scale-up, offers a unique 2,2,3-substitution pattern, and delivers chromanes with diversified core substitution patterns. The unprecedented tolerance of strong electron-withdrawing substituents at the phenol renders the protocol indispensable to access the otherwise inaccessible chromane chemical space that is important for medicinal chemistry campaigns.

Diastereodivergent synthesis of chromeno[2,3-]chromenes by tuning all of the reactivity centers of isocyanoacetate.

A novel diastereodivergent tricyclization of isocyanoacetates with -quinone methides was accomplished for the efficient synthesis of chromeno[2,3-]chromene derivatives. All three reactive centers of isocyanoacetate reacted sequentially with two -QMs, affording the products with four adjacent stereocenters in a diastereoselective manner. The asymmetric version was preliminarily investigated.

Chemoselective Trimerization of Isocyanides: De Novo Synthesis of 2-Indole-Substituted Quinolines and Pyridines.

A catalyst-free chemoselective trimerization reaction of readily available isocyanides is described. This domino reaction provides facile access to a wide range of 2-(indol-2-yl)-quinolines and 2-(indol-2-yl)-pyridines in moderate to excellent yields. A "head to head" heterodimerization of two isocyanides is proposed as the key step of this reaction.

Cu/base co-catalyzed [3+3] cycloaddition for the synthesis of highly functionalized 4-fluoropyridines.

An efficient, straightforward and general method for the synthesis of highly functionalized 4-fluoropyridines was developed a cooperative copper- and base-catalyzed [3+3] cycloaddition of active methylene isocyanides with difluorocyclopropenes. The resulting 4-fluoropyridines can be readily diversified by various nucleophiles.

Dinucleophilic Reactivity of Isocyanoacetate: Base-Catalyzed One-Pot Access to 4-Azafluorenes and 4-Azafluorenones.

A base-catalyzed double annulation of isocyanoacetates with various enynones has been developed for the expeditious synthesis of 4-azafluorene and 4-azafluorenone derivatives. Against the well-known 1,3-dipolar reactivities, the active methylene and isocyano groups of isocyanoacetate serve as nucleophiles in this domino transformation.

Highly Stable Copper(I)-Thiacalix[4]arene-Based Frameworks for Highly Efficient Catalysis of Click Reactions in Water.

Environmentally friendly metal-organic frameworks (MOFs) have gained considerable attention for their potential use as heterogeneous catalysts. Herein, two Cu -based MOFs, namely, [Cu Cl L]⋅CH OH⋅1.5 H O (1-Cl) and [Cu Br L]⋅DMF⋅0.

A Calix[4]resorcinarene-Based [Co] Coordination Cage for Highly Efficient Cycloaddition of CO to Epoxides.

The design and synthesis of polynuclear metal cluster-based coordination cages is of considerable interest due to their appealing structural characteristics and potential applications. Herein, we report a calix[4]resorcinarene-based [Co] coordination cage, [Co(TPC4R-I)(1,3-BDC)(μ-OH)(HO)(DMF)]·7DMF·23HO (), assembled with 2 bowl-shaped calix[4]resorcinarenes (TPC4R-I), 10 angular 1,3-benzenedicarboxylates (1,3-BDC), and 12 Co(II) cations. Remarkably, it is shown to be a highly efficient recyclable heterogeneous catalyst for CO conversion due to its exposed Co(II) Lewis acid sites.

Polyoxometalate-Bridged Cu(I)- and Ag(I)-Thiacalix[4]arene Dimers for Heterogeneous Catalytic Oxidative Desulfurization and Azide-Alkyne "Click" Reaction.

Two remarkable polyoxometalate-bridged Cu(I)- and Ag(I)-thiacalix[4]arene dimers, namely, [Cu(SiWO)(L)(DMF)]·2EtOH·DMF () and [Ag(PMoO)(L)]·OH (), were prepared by using a new thiacalix[4]arene, metal cation and polyoxometalate (L = tetra[2-(ethylthio)-1-methyl-1-imidazole]-thiacalix[4]arene). In and , two thiacalix[4]arenes were linked together by one [SiWO] or [PMoO] anion via two metal cations to give a molecular dimer. Further, adjacent dimers were extended into a high-dimensional supramolecular architecture through hydrogen bonds.

Calix[4]resorcinarene-based [Co] coordination cages mediated by isomorphous auxiliary ligands for enhanced proton conduction.

We herein propose a design assembly of calix[4]resorcinarene-based proton-conductive [Co16] coordination cages (1-SO3H and 1-OH) by carefully mediating the acidic sites of isomorphous auxiliary ligands. Markedly, 1-SO3H exhibits a proton conductivity that increased about 1 order of magnitude relative to its counterpart 1-OH, reaching 1.35 × 10-2 S cm-1 at 90 °C and under 98% relative humidity.

Metal-Assembled, Resorcin[4]arene-Based Molecular Trimer for Efficient Removal of Toxic Dichromate Pollutants and Knoevenagel Condensation Reaction.

Self-assembly of resorcin[4]arene-based coordination cages involving more than two resorcin[4]arenes poses significant challenges for the requirements of suitable functionalized resorcin[4]arene ligands and metals. Here, we report an unusual example of a metal-coordinated, resorcin[4]arene-based molecular trimer (1-NO), composed of three resorcin[4]arenes and three Cd(II) cations. In particular, 1-NO features efficient and selective removal of environmentally toxic dichromate (CrO) anions.

Base-mediated regioselective [3+2] annulation of ketenimines and isocyanides: efficient synthesis of 1,4,5-trisubstituted imidazoles.

A novel base-mediated regioselective [3+2] annulation of active methylene isocyanides with ketenimines has been developed. In the presence of t-BuOK, a wide range of ketenimines readily react with active methylene isocyanides in DMF at 40 °C to afford 1,4,5-trisubstituted imidazoles efficiently.

Silver-Catalyzed Nucleophilic Addition of β-Dicarbonyls to Isocyano Group: Facile Access to Indolin-3-ol Derivatives.

A domino silver-catalyzed intermolecularly nucleophilic addition of β-dicarbonyls to the isocyano group and cyclization of the imidoyl silver sequence was developed for the direct and efficient synthesis of indolin-3-ol derivatives. This domino transformation tolerates a range of readily available o-acyl arylisocyanides and 1,3-dicarbonyls under an operationally simple procedure. Triple roles of silver carbonate are demonstrated in this reaction: (1) activation of isocyano group, (2) formation of enolate, and (3) promotion the nucleophilic reactivity of imidoyl intermediate.

[1 + 2 + 3] Annulation as a General Access to Indolo[3,2- b]carbazoles: Synthesis of Malasseziazole C.

A formal [1 + 2 + 3] annulation of methyleneindolinones with o-alkenyl arylisocyanides has been developed for the general and efficient synthesis of both symmetrical and unsymmetrical indolo[3,2- b]carbazoles. The chemoselectivity of this domino reaction was tuned by a tethered alkenyl group, which enables successive formation of three new bonds and two rings from readily accessible starting materials in a single operation. Furthermore, this methodology was used as a key step in the synthesis of the alkaloid malasseziazole C.

Rhodium-Catalyzed Tandem Reaction of Isocyanides with Azides and Oxygen Nucleophiles: Synthesis of Isoureas.

A novel rhodium-catalyzed tandem reaction of isocyanides with azides and various oxygen nucleophiles has been developed. The reaction provides a simple and highly efficient one-pot synthesis of various N-sulfonyl/acylisoureas with broad substrate scope in an atom-economical manner from readily available starting materials in a highly stereoselective manner.

Rhodium(iii)-catalyzed three-component cascade synthesis of 6H-benzo[c]chromenes through C-H activation.

A three-component cascade reaction is described that provides concise access to 6H-benzo[c]chromenes via Rh(iii)-catalyzed annulation of aryl ketone O-acyloximes, quinones and acetone. Acetone acts as a co-solvent and as a reactant. This reaction shows high efficiency, atom- and step-economy, good substrate scope, excellent functional group compatibility and gives the products in good yields.