Mild and efficient construction of nitrogen-containing heterocycles from -ethynylbenzaldehydes and anilines.

A mild and transition-metal-free strategy for the synthesis of isoindolin-1-imines and isoquinolinium salts has been developed using -ethynylbenzaldehydes and anilines. HFIP was employed as an effective promoter, facilitating nucleophilic addition and annulation to afford diverse isoindolin-1-imines in good yields. Alternatively, isoquinolinium salts were obtained by addition of ammonium iodide.

Palladium-Catalyzed "Cut-and-Sew" Reaction of C(sp)-NC: Direct Synthesis of Bulky Nitriles Containing an All-Carbon Quaternary Center.

A palladium-catalyzed carbo-cyanation reaction for synthesizing bulky nitriles with an all-carbon quaternary center via a "cut-and-sew" process of isocyanides is presented. The reaction proceeds through oxidative addition of indole-derived carbonate to Pd(0), followed by decarboxylation, migratory insertion, and the formation of a ketenimine intermediate. A geminate radical pair is formed, leading to radical coupling and the final bulky nitrile product.

Catalytic α-alkylation of α-fluoro-α-2-azaaryl carbonyl compounds with nonconjugated alkenes.

Herein, we present a novel hydrocarbofunctionalization of nonconjugated alkenes for the synthesis of azaarenes possessing a fluorine-bearing quaternary carbon center. The reaction utilizes easily accessible α-fluoro-α-2-azaaryl carbonyl compounds and alkenes as starting materials and PdCl as the catalyst without exogenous bases or additives. The simple operation, good tolerance towards azaarenes and easily scalable synthesis further highlight the potential application of this protocol.

Cobalt-Catalyzed Cascade Synthesis of 5-Amino-1,2,4-triazolo[1,5-]quinazoline Derivatives via Multiple C-N Bonds Construction.

A cobalt-catalyzed three-component cascade reaction for the synthesis of functionalized 5-amino-1,2,4-triazolo[1,5-]quinazoline derivatives is presented. The reaction involves -cyanoaryl isocyanides, azides, and hydrazides, giving products in good to excellent yields. The protocol is highly scalable, as demonstrated by a gram-scale reaction of bioactive CGS-15943, providing a robust, efficient method for synthesizing triazoloquinazoline derivatives and offering significant potential for drug discovery and further modifications.

Asymmetric Synthesis of Azahelicenes via CPA-Catalyzed Kinetic Resolution.

The azahelicenes are structurally fascinating and practically useful chiral scaffolds, but their synthesis, especially in a catalytically asymmetric manner, is rather challenging. Herein, we report a CPA-catalyzed transfer hydrogenation process, which enables a rapid kinetic resolution of aza[6]helicenes. The established strategy provides facile access to enantioenriched aza[6]helicenes and tetrahydro[6]helicenes from easily available starting materials.

Palladium-catalyzed cascade cyclization of isocyanides with di-(-iodophenyl)sulfonylguanidines: access to heterocyclic fused quinazolines.

A palladium-catalyzed cascade cyclization reaction of di--iodophenyl sulfonylguanidines with isocyanides for the efficient and selective synthesis of 5- or 6-membered heterocyclic fused quinazolines has been developed. Diverse functional groups are well tolerated, and this method has been successfully applied to a larger scale synthesis.

Radical-Initiated Dearomative Annulation of Tryptamine-Derived Isocyanides: Selective Synthesis of CF-Substituted β-Aza-spiroindolines and β-Carbolines.

A mild approach for synthesizing CF-substituted β-aza-spiroindolines and β-carbolines from tryptamine-derived isocyanides via site-selective radical annulations has been reported. The crucial role of C2 substituents in the selective annulation process has been clarified. The approach shows good generality and practical applicability, highlighting its effectiveness and versatility.

Pd-Catalyzed Dual C-H Activation/Cyclization: Convergent and Divergent Synthesis of 1-Azahelicenes.

Herein, we report a convergent synthesis of 1-azahelicenes using easily available quinoline derivatives and cyclic diaryliodonium salts as starting materials. This reaction undergoes a palladium-catalyzed dual C-H activation/cyclization process to give facile access to a wide range of 1-aza[5]helicenes and 1-aza[6]helicenes with abundant functional groups (including F, Cl, Br, I, CF, SeR, SR, and heteroaryl) in moderate to excellent yields, thereby providing new opportunities to fine-tune the properties of the helicene backbone. In addition, the obtained products could be further transformed into helicene-based Lewis base catalysts and redox switch materials easily.

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.

Palladium-catalyzed carbomonofluoromethylation of unactivated alkenes: rapid access to γ-monofluoromethyl carboxylic acid derivatives.

Herein, we report a palladium-catalyzed regioselective carbomonofluoromethylation of unactivated alkenes. The reaction uses easily available fluorobis(phenylsulfonyl)methane (FBSM) as a fluoromethylating reagent, and proceeds smoothly with a wide variety of carbon electrophiles, including (hetero)aryl iodides, styrenyl iodides and TIPSBr. A range of remote γ-CHF/CDF carboxylic acid derivatives were constructed rapidly after a simple reductive desulfonylation step.

Coupling-Spirocyclization Cascade of Tryptamine-Derived Isocyanides with Iodonium Ylides and Despirocyclization Reactions.

A cobalt(II)-catalyzed coupling-cyclization cascade reaction between tryptamine-derived isocyanides and iodonium ylides is investigated, which allowed for the synthesis of different types of spiroindoline compounds by variation of substituents at the N1- and C2-positions in the indole skeleton. More interesting is that the spiroindoline products could undergo despirocyclization in the presence of amines, enabling efficient construction of enamine compounds.

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.

NBS-induced intramolecular annulation reactions for the divergent synthesis of fused- and spirocyclic indolines.

An NBS-induced intramolecular annulation of 3-(1-indol-3-yl)--alkoxypropanamide is described. The reactions proceed well and quickly under mild conditions with the help of a base. It was found that C2-substituents on the indole ring in 3-(1-indol-3-yl)--alkoxypropanamide have a great influence upon the reaction.

Synthesis of Azoxy Compounds: from Copper Compounds to Mesoporous Silica-Encaged Ultrasmall Copper Catalysts.

Azoxy compounds have aroused extensive attention due to their unique biological activities, but the chemical synthesis of these compounds often suffers from limitations due to their requirement for stoichiometric oxidants, high costs, and restricted substrate range. Herein, a series of azoxy compounds were constructed via facile coupling reactions by using cost-effective N-methoxyformamide and nitroso compounds over Cu-based catalysts, affording high product yields with excellent tolerance of functional groups. Significantly, the mesoporous silica nanosphere-encapsulated ultrasmall Cu (Cu@MSN) catalyst was developed via a one-pot synthetic method and first used for the synthesis of azoxy compounds.

Divergent Synthesis of Pentacyclic Isoindolinones Enabled by Sequential Insertion of Two Different Isocyanides and Acid Promoted Cyclization of Ketenimines.

A palladium-catalyzed multicomponent reaction involving -bromobenzaldehydes and two different isocyanides was developed to assemble series of isoindolinones with spiroindolenine or azepinoindole skeletons. This sequential insertion reaction features mild conditions, a wide substrate scope, and high efficiency. Preliminary mechanistic study indicated that the difference in steric hindrance between isocyanide components is crucial when regulating the reaction sequence, whereas the ligand also played an important role during the whole process.

Palladium-Catalyzed Regioselective Diarylation/Deamination of Homoallylamines: Modular Assembly of 1,1,4,4-Tetraaryl-1,3-butadienes.

Herein, a novel palladium-catalyzed regioselective diarylation/deamination of homoallylamines is described. During the process, a ubiquitous free amine (NH) was used as the directing group to accomplish the regioselective δ,δ-diarylation and it was removed in situ to form the privileged 1,1,4,4-tetraaryl-1,3-butadiene motif. This chelate-controlled Heck-type approach eliminates the traditional need of preinstalled and hard removable directing groups, proceeds under simple conditions, and exhibits good tolerance to a wide range of synthetically useful functional groups.

Visible-light photocatalytic radical addition-translocation-cyclization to construct sulfonyl-containing azacycles.

Herein, a novel visible-light photocatalytic radical addition-translocation-cyclization (RATC) approach for the efficient synthesis of sulfonyl-containing azacycles is described. The reaction delivers a wide range of monocyclic, bicyclic and polycyclic azacycles by using easily prepared sodium sulfinates and -homopropargylic amines as starting materials. Instead of the traditionally used toxic tin reagents and thermally hazardous azos in the RATC process, clean, renewable and sustainable visible light combined with a catalytic amount of photosensitizer is used in this process.

-Stereoselective C3-Spirocyclization and C2-Amination of 3-(2-Isocyanoethyl)indole Using ,-Cyclic Azomethine Imines.

By utilizing an underexplored reaction mode of ,-cyclic azomethine imines, a catalyst-free [1+2+3] cycloaddition/N-N bond cleavage sequential reaction for accessing spiroindolines with -stereoselectivity was developed. On the basis of experimental results and DFT calculations, peroxide and ethereal solvent were identified to trigger the hydrogen abstraction of the unstable [1+2+3] cycloaddition adducts, followed by homolytic cleavage of the N-N bond and hydrogen absorption.

Correlation Between IVIM-DWI Parameters and Pathological Classification of Idiopathic Orbital Inflammatory Pseudotumors: A Preliminary Study.

Objective: To investigate the correlation between intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and the pathological classification of idiopathic orbital inflammatory pseudotumors (IOIPs).

Methods: Nineteen patients who were diagnosed with IOIPs (a total of 24 affected eyes) between November 2018 and December 2020 were included in the study. All the patients underwent magnetic resonance imaging orbital plain scans and IVIM-DWI multiparameter scans before an operation.

Ruthenium(II)-Catalyzed Chelation-Assisted Desulfitative Arylation of Benzo[h]quinolines with Arylsulfonyl Chlorides.

Herein, a novel chelation-assisted C-H arylation reaction of benzo[h]quinoline is described. This transformation, using [RuCl(-cymene)] as the catalyst and cheap and easily accessible arylsulfonyl chlorides as the arylation source, featured simple reaction conditions, a broad substrate scope, and functional group tolerance. The successful application of some bioactive-molecule-based sulfonyl chlorides further highlighted the potential utility and importance of this desulfitative C-H arylation protocol.

Ligand-Promoted Nickel-Catalyzed -Selective Carboxylation of Anisoles.

It has always been a challenge in free radical chemistry to control site selectivity during the reaction of free radicals with aromatic rings. Herein, we report the site-selective carboxylation of anisoles through the direct reaction of the bromoform radical with a benzene ring at the position under the assistance of 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline with nickel(II) as the catalyst. A wide variety of anisoles were compatible, leading to -carboxylated products in moderate to good yields.

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

A palladium-catalyzed three-component reaction of isocyanides, 2,2,2-trifluoro--(2-iodophenyl)acetimidoyl chlorides, and amines for the one-pot synthesis of 2-(trifluoromethyl)quinazolin-4(3)-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.

Divergent synthesis of α-functionalized amides through selective N-O/C-C or N-O/C-C/C-N cleavage of aza-cyclobutanone oxime esters.

Herein, a novel sequential ring opening reaction of aza-cyclobutanone oxime esters with isocyanides is described. The reaction proceeded smoothly under redox-neutral and mild conditions, leading to a divergent synthesis of α-cyanomethylaminoamides, α-acyloxyamides and α-acylaminoamides. In these transformations, a selective N-O/C-C or N-O/C-C/C-N cleavage was achieved only by changing the iron-catalyst system.

Divergent Reaction of Isocyanides with -Bromobenzaldehydes: Synthesis of Ketenimines and Lactams with Isoindolinone Cores.

A divergent reaction of isocyanides with -bromobenzaldehydes for the synthesis of isoindolinone-derived ketenimines and lactams was disclosed. The reaction features readily available reactants, relatively mild conditions, and high yields of products. Ketenimines could be applied in further transformations for access to other functional molecules.