Precise Synthesis of Diastereomers of Spiro-oxindole Derivatives through Dynamic Covalent Transformation.

In this study, [1+2+2] cyclization of tryptamine-derived isocyanides with 3-ylideneoxindoles was systematically investigated. A series of structurally complex spiro-oxindole derivatives were obtained. Characteristic dynamic covalent chemistry was observed and confirmed by experiments and density functional theory calculation. Through the regulation of the solvent, temperature, and time, the precise and stereodivergent synthesis of spiro-oxindoles was achieved.

A Novel Approach to α-Arylacetonitrile Skeletons via para-Selective Alkylation of Protected Anilines.

A ruthenium-catalyzed para-selective alkylation of protected anilines to construct α-arylacetonitrile skeletons has been reported. We firstly disclosed the ethyl 2-bromo-2-cyanopropanoate was an effective alkylating reagent in ruthenmuim-catalyzed remote-selective C-H functionalization. A wide variety of α-arylacetonitrile skeletons can be directly obtained with moderate to good yields. Importantly, the products contain both nitrile and ester groups guaranteeing its direct transformation into other useful synthetic units, indicating the synthetic importance of this method.

[4 + 1 + 1] Tandem Cyclization Reaction Involving Isocyanides: Access to 2-(Trifluoromethyl)quinazolin-4(3H)-imines.

A palladium-catalyzed three-component reaction of isocyanides, 2,2,2-trifluoro-N-(2-iodophenyl)acetimidoyl chlorides, and amines for the one-pot synthesis of 2-(trifluoromethyl)quinazolin-4(3H)-imines was described. The protocol features a wide substrate scope, high efficiency, and readily available raw materials.

A Radical Addition/Cyclization and Se-Group Transfer Strategy for the Facile Synthesis of Se-Containing Cyclopentenes under Metal-Free and Peroxide-Free Conditions.

A novel intermolecular radical addition/cyclization and Se-group transfer reaction of terminal alkynes and unsaturated alkyl selenide is presented which offers a straightforward and facile approach for the synthesis of valuable Se-containing cyclopentenes. Remarkable features of this strategy include easily accessible starting materials, metal-free and peroxide-free conditions, high atom economy, simple operation and broad substrate scope. More importantly, the reaction is easy to scale up and can be extended to the construction of six-membered carbon ring.

Amidation-Ketonization-Selenation of Terminal Alkynes Using TEMPO and Elemental Selenium.

Herein, we present a novel silver- or copper-mediated direct amidation-ketonization-selenation of terminal alkynes for the synthesis of α-oxo-selenoamides. The reaction utilized easily accessible elemental selenium as the source of selenium. In addition, the 18O labeling experiment revealed that TEMPO is the oxygen source of the carbonyl group. The reaction takes advantage of an unsaturated C≡C bond to construct new C═O, C═Se, and C-N bonds in one step.

Cascade Reaction of Tryptamine-Derived Isocyanides with Nitrile Oxides: Construction of Oxazine Fused-Spiroindoline Derivatives.

A one-step cascade reaction of tryptamine-derived isocyanides with in situ generated nitrile oxides for the synthesis of fused spiroindolines was described. The desired products could be efficiently synthesized in moderate to good yields (42-87%). The protocol features mild conditions, wide substrate scope, and high efficiency.

Synthesis of Spiro 3,3'-Cyclopropyl Oxindoles Via N-Bromosuccinimide-Mediated Ring-Closing and Contraction Cascade.

An N-bromosuccinimide-mediated cascade reaction involving the cyclization/oxygen-migration/ring-contraction process of 3-(ß, ß-diaryl) indolylethanol was disclosed. A variety of spiro 3,3'-cyclopropyl oxindole derivatives were efficiently synthesized in good yields under mild reaction conditions. A possible mechanism was suggested based on intermediate isolation and computational studies.

Iron-Catalyzed Highly para-Selective Difluoromethylation of Arenes.

Direct functionalization of a C-H bond at either the meta or para position by only changing the catalyst system poses a significant challenge. We herein report the [Fe(TPP)Cl]-enabled, selective, C-H difluoromethylation of arenes using BrCF2CO2Et as the difluoromethylation source, which successfully altered the selectivity from the meta to the para position. A preliminary mechanistic study revealed the iron porphyrin complex not only activated the aromatic ring but also induced para selectivity due to the influence of ligand sterics.

Base-Promoted Multicomponent Reactions: A Synthesis of 2-Amino-1,3-selenazole Derivatives.

New practical synthesis of 2-amino-1,3-selenazole with transition metal-free multicomponent reaction is reported here. A series of 2-amino-1,3-selenazole derivatives were afforded by the nucleophilic addition of amines to isoselenocyanate formed in situ, followed by Michael addition reaction and aromatization. The products were isolated from moderate to excellent yields.

Copper-Catalyzed Chemoselective Cyclization Reaction of 2-Isocyanoacetophenone: Synthesis of 4-Hydroxyquinoline Compounds.

A copper-catalyzed intramolecular cyclization reaction of 2-isocyanoacetophenone derivatives to afford 4-hydroxyquinolines chemoselectively is described. The transformation proceeds through enol tautomerism and a subsequent C-C bond formation. Compared to previous methods, this study provides a new protocol for the construction of 4-hydroxyquinoline compounds from functionalized isocyanides under mild conditions.

Iron(iii) chloride-promoted cyclization of α,ß-alkynic tosylhydrazones with diselenides: synthesis of 4-(arylselanyl)-1H-pyrazoles.

A highly efficient iron(iii) chloride-promoted cyclization between α,ß-alkynic tosylhydrazones and diselenides to form a 4-(arylselanyl)-1H-pyrazole skeleton is studied. This reaction forms C-N and C-Se bonds in one step by utilizing inexpensive iron(iii) chloride instead of expensive transition metal additives. This strategy features easily synthesized substrates, mild reaction conditions and high tolerance to functional groups.

Synthesis of organoselenyl isoquinolinium imides via iron(III) chloride-mediated tandem cyclization/selenation of N'-(2-alkynylbenzylidene)hydrazides and diselenides.

This report describes the synthesis of organoselenyl isoquinolinium imides through a tandem cyclization between N'-(2-alkynylbenzylidene)hydrazides and diselenides. The reaction was carried out at room temperature under an ambient atmosphere using cheap iron(iii) chloride as the metallic source. The strategy shows good tolerance to a broad range of N'-(2-alkynylbenzylidene)hydrazides and diselenides, and forms C-N and C-Se bonds in one step. The obtained product is further transformed into a bioactive H-pyrazolo[5,1-a]isoquinoline skeleton easily via a silver catalyzed [3 + 2] cycloaddition.

Hydrogen-Bonding-Promoted Cascade Rearrangement Involving the Enlargement of Two Rings: Efficient Access to Polycyclic Quinoline Derivatives.

An efficient cascade reaction of tryptamine-derived isocyanides with C,N-cyclic azomethine imines is described. The polycyclic pyrrolo[2,3-c]quinoline derivatives, which benefited from rearrangement process driven by hydrogen bonding, could be directly assembled in moderate to good yields (40-87 %) under metal-free and mild conditions. This transformation involved four new heterocyclic rings formations and uniquely, ring opening of indole as well as ring expansion of C,N-cyclic azomethine imine. Both experimental and DFT studies provided guidance on the in-depth insight into the reaction pathways and hydrogen bonding was identified to lower the free energy barrier in transition states. This work constitutes a rare example of tryptamine-derived isocyanide-based cascade reactions, and potentially could be a powerful synthetic strategy for accessing polycyclic analogues involved in natural products.

Nickel-Catalyzed Thiolation and Selenylation of Cycloketone Oxime Esters with Thiosulfonate or Seleniumsulfonate.

A nickel-catalyzed ring opening and, subsequently, reductive cross-coupling of cycloketone oxime esters with thiosulfonate or seleniumsulfonate are reported, which involves C-C bond cleavage and C(sp3)-S or C(sp3)-Se bond formation. Notably, S-aryl/alkyl sulfonothioates and Se-alkyl seleniumsulfonothioates could be employed in this reaction to afford a variety of 1° and 2° alkyl sulfides, aryl sulfides, and 1° and 2° alkyl selenides in one step. This strategy features easily available substrates and mild reaction conditions.

Visible Light-Induced Co- or Cu-Catalyzed Selenosulfonylation of Alkynes: Synthesis of ß-(Seleno)vinyl Sulfones.

A visible light-induced Co- or Cu-catalyzed selenosulfonylation of alkynes for the synthesis of ß-(seleno)vinyl sulfones is demonstrated. This method utilizes a low-cost cobalt salt or metal copper as the catalysts. The reaction goes through a photoinduced free radical addition of selenosulfonates to alkynes for the 1,2-selenosulfonylation of alkynes under mild conditions.

Nickel-Catalyzed Defluorinative Reductive Cross-Coupling Reaction of gem-Difluoroalkenes with Thiosulfonate or Selenium Sulfonate.

A nickel-catalyzed defluorinative reductive cross-coupling of gem-difluoroalkenes with thiosulfonate or selenosulfonates is described. The reaction involves the formation of thiolated or selenylated monofluoroolefins via regioselective C-F bond cleavage and C-S or C-Se bond formation and features easily available substrates, mild reaction conditions, and high E-selectivity. One of the derivatives by further cross coupling with PhMgBr exhibited an aggregation-induced emission enhancement effect.

Palladium Catalyzed Insertion Reaction of Isocyanides with 3-Arylisoxazol-5(4H)-ones: Synthesis of 4-Aminomethylidene Isoxazolone Derivates.

A palladium catalyzed insert reaction of isocyanides to 3-arylisoxazol-5(4H)-ones for the construction of 4-aminomethylidene isoxazolone derivates is reported. In this transformation, only the C-H bond of the methylene group was involved while the remaining ring structure was retained. In general, this work provided a new protocol for the synthesis of 4-aminomethylidene isoxazolones.

Synthesis of Polysubstituted Maleimides via Metal-Free Cascade Reaction of Isocyanides and α-Diazoketones.

In this paper, synthesis of polysubstituted maleimides was described via cascade reaction of isocyanides and α-diazoketones. This strategy features readily available substrates, high atom-economy and metal-free conditions. A variety of valuable polysubstituted maleimides are assembled in good yields.

Rational Design and Synthesis of a Metalloproteinase-Activatable Probe for Dual-Modality Imaging of Metastatic Lymph Nodes in Vivo.

Lymphatic metastasis is an important prognostic indicator for cancer progression. It is therefore considerably meaningful to develop molecularly targeted imaging probes for noninvasive and accurate identification of metastatic lymph nodes (MLNs) at early stages of tumor metastasis. Herein, we report a novel matrix metalloproteinase-2 (MMP-2)-activatable probe constructed with a near-infrared dye (Cy5), a quencher (QSY21), and a tumor-targeting peptide cRGD covalently linked through a radionuclide (125I)-labeled peptide substrate for accurate detection of MLNs. Upon cleavage with activated MMP-2, the above probe emitted MMP-2 concentration-dependent near-infrared fluorescence, which allows sensitive and specific visualization of MLNs via both optical and single-photon emission computed tomography imaging techniques. We thus envision that this probe would serve as a useful tool for studying tumor-induced lymphangiogenesis.

Cascade Trisulfur Radical Anion (S3•-) Addition/Electron Detosylation Process for the Synthesis of 1,2,3-Thiadiazoles and Isothiazoles.

Trisulfur radical anion (S3•-) mediated reactions with in situ formed azoalkenes and α,ß-usaturated N-sulfonylimines for the construction of 1,2,3-thiadiazoles and isothiazoles has been developed. S3•- is in situ generated from potassium sulfide in DMF. These two approaches provide a new, safe, and simple way to construct 4-subsituted 1,2,3-thiadiazoles, 5-subsituted 1,2,3-thiadiazoles, and isothiazole in good yields. The reactions include the formation of the new C-S and N-S bonds via S3•- addition and electron detosylation under mild conditions.