Enantioselective Synthesis of Isoindolinone by Sequential Palladium-Catalyzed Aza-Heck/Suzuki Coupling Reaction.

We present a tandem aza-Heck/Suzuki cross-coupling reaction of -phenyl hydroxamic ethers with readily available arylboronic and alkenyl boronic acids. This protocol is enabled by a palladium catalyst paired with chiral phosphoramidite ligands, particularly under mild reaction conditions, yielding efficient and succinct synthetic routes to chiral isoindolinones with high enantioselectivity. Furthermore, this reaction exhibits excellent functional group compatibility and a rich diversity of subsequent transformations.

Palladium-Catalyzed Domino Carboetherification Reactions: Synthesis of Bis-Heterocycles Bearing Isoxazoline and Methyleneindole Motifs.

A novel and highly efficient Pd-catalyzed approach for the synthesis of bis-heterocycles featuring both isoxazoline and methyleneindole motifs is demonstrated. The in situ formation of vinyl Pd(II) species through an alkyne-tethered carbamoyl chloride cyclization is crucial, and the innovative Pd-catalyzed carboetherification of β,γ-unsaturated oximes with vinyl Pd(II) species has been developed. This method is not only operationally straightforward but also exhibits a broad substrate scope and excellent functional group tolerance.

Synthesis of Indole- and Benzofuran-Based Benzylic Sulfones by Palladium-Catalyzed Sulfonylation of -Iodoaryl Allenes.

A highly efficient palladium-catalyzed domino coupling reaction of -iodoaryl allene with sodium sulfonates under mild conditions is described. This novel method provides a practical protocol to access diverse indole- and benzofuran-containing sulfones by simultaneous construction of C(sp)-C(sp) bond and a C(sp)-S bonds in one pot. The salient features of this transformation include simple operations, broad substrate scope, and good functional group tolerance.

Synthesis of Sulfoxides by Palladium-Catalyzed Arylation of Sulfenate Anions with Aryl Thianthrenium Salts.

A novel and highly efficient Pd-catalyzed arylation of sulfenate anions with aryl thianthrenium salts is demonstrated. This procedure provides a practical protocol to synthesize various diaryl and alkyl aryl sulfoxides in moderate-to-good yields. The new approach shows mild reaction conditions, broad substrate scope, and good functional group tolerance.

Construction of Diverse Fused Chromene Frameworks via Isocyanide-Based Three-Component Reaction.

A convenient synthetic protocol for diverse fused chromenes was successfully developed by a three-component reaction of alkyl isocyanides, dialkyl but-2-ynedioates, and various cyclic 1,3-dipolarophiles containing -hydroxyphenyl group. In the absence of any catalyst, the three-component reaction of alkyl isocyanides, dialkyl but-2-ynedioates, and 3-(-hydroxyarylidene)indolin-2-ones in tetrahydrofuran at 60 °C resulted in unique functionalized spiro[cyclobuta[]chromene-1,3'-indolines] in good yields and with high diastereoselectivity. However, the similar three-component reaction with 2-(5-halo-2-hydroxyarylidene)indolin-2-ones afforded unexpected chain products in satisfactory yields.

Rapid construction of tricyclic tetrahydrocyclopenta[4,5]pyrrolo[2,3-]pyridine via isocyanide-based multicomponent reaction.

An efficient protocol for the synthesis of polyfunctionalized tetrahydrocyclopenta[4,5]pyrrolo[2,3-]pyridine-3,4b,5,6,7(1)-pentacarboxylates was developed by a three-component reaction. In the absence of any catalyst, the three-component reaction of alkyl isocyanides, dialkyl but-2-ynedioates and 5,6-unsubstituted 1,4-dihydropyridines in refluxing acetonitrile afforded polyfunctionalized tetrahydrocyclopenta[4,5]pyrrolo[2,3-]pyridine-3,4b,5,6,7(1)-pentacarboxylates in high yields and with high diastereoselectivity. The reaction was finished by in situ generation of activated 5-(alkylimino)cyclopenta-1,3-dienes from addition of alkyl isocyanide to two molecules of but-2-ynedioates and sequential formal [3 + 2] cycloaddition reaction with 5,6-unsubstituted 1,4-dihydropyridine.

Synthesis of Spiro[indoline-pyridine]-dicarboxylates and Substituted Alkylidene Oxindoles by Azomethine Ylides and MBH Carbonates of Isatins.

We have developed an efficient protocol for the synthesis of spiro[indoline-pyridine]dicarboxylates and substituted alkylidene oxindoles through [3 + 3] cycloaddition and Michael addition individually by azomethine ylides and various MBH carbonates of isatins. The selective generation of cyclic products and chain products was achieved by changing the substituents at the 3-position of the oxindoles. The features of this method include convenient catalysts, mild reaction conditions, and broad substrate scopes.

Enantioselective Synthesis of Isoindolinone by Palladium-Catalyzed Aminoalkynylation of -Phenyl Hydroxamic Ethers with Alkynes.

A highly efficient palladium-catalyzed asymmetric tandem aza-Heck/Sonogashira coupling reaction of -phenyl hydroxamic ethers with terminal alkynes is described. This protocol enables versatile access to challenging chiral isoindolinone derivatives bearing a quaternary stereogenic center. The palladium-catalyzed aminoalkynylation reaction shows broad functional group tolerance and allows the straightforward preparation of isoindolinones with high efficiency and excellent enantioselectivity under mild conditions.

Synthesis of Bis-Heterocycles Bearing Methyleneindole Motifs by Pd-Catalyzed Domino Reaction.

A highly robust, general, and practically simple palladium-catalyzed domino bicyclization strategy is presented to synthesize nitrogen-containing bis-heterocycles bearing methylene indole motifs from alkyne-tethered carbamoyl chlorides and β,γ- or γ,δ-unsaturated hydrazones. The salient features of this transformation include broad substrate scope, good functional group tolerance, ease for scale-up, and convenient conversion.

Direct Regioselective Reductive Allylation of Imines: Application to Synthesis of Oxazines with Halogenated Reagent.

Oxazines are an important class of compounds in oxazine ligands and medical chemistry. Here, we describe a linear-selective allylation of imines with allyl electrophiles via cross-electrophile coupling reactions, followed by cyclization with halogenated reagents, providing a new strategy to afford oxazine compounds with a tetrasubstituted carbon center. Mechanistic studies indicate that α-amino carbanion, generated by successive single-electron transfer processes, is a key intermediate for nucleophile attack on π-allylpalladium in photoredox/palladium catalysis.

Regioselective and Diastereoselective Construction of Diverse Dispiro-Indanone-Fluorenone-Oxindole Motifs.

A convenient synthetic protocol for regioselective and diastereoselective construction of complex dispiro-indanone-fluorenone-oxindole motifs was developed by the base-promoted annulation reaction of bindone and MBH carbonates of isatins by adjusting reaction conditions. DABCO promoted the annulation reaction of bindone and MBH carbonates of isatins in DCM at room temperature, affording dispiro[indene-2,4'-fluorene-1',3″-indoline] derivatives in good yields and with high diastereoselectivity. Triethylamine promoted the annulation reaction of two molecular 1,3-indanediones and MBH esters of isatins in ethanol at elevated temperature and selectively gave dispiro[indene-2,4'-fluorene-3',3″-indolines] in moderate yields.

Construction of diverse spirooxindoles a domino reaction of arylamines, but-2-ynedioates and 3-hydroxy-3-(indol-3-yl)indolin-2-ones.

An iodine-promoted domino reaction of arylamines/benzylamines, dialkyl but-2-ynedioates and 3-hydroxy-3-(indol-3-yl)indolin-2-ones showed very interesting molecular diversity. The reaction in acetonitrile at 65 °C in the presence of 30% mmol I resulted in spiro[indoline-3,1'-pyrido[4,3-]indoles] in satisfactory yields. When anilines without -substituents were used in the reaction, a direct substitution of the hydroxyl group to 2-(phenylamino)maleate at the -position of aniline gave chain products in good yields.

Construction of Unique Spiro[dibenzo[,]azulene-6,2'-indenes] via Unprecedented Annulation of -C-H Bond of Benzylidene Group.

The domino reaction of alkyl and aryl isocyanides with two molecules of 2-arylidene-1,3-indanediones in acetonitrile at 80 °C resulted in unique functionalized spiro[dibenzo[,]azulene-6,2'-indenes] in good yields, in which the two 2-arylidene-1,3-indanediones acted as different building blocks to construct the polycyclic system. More importantly, the unprecedented anticipation of the ortho-position of benzylidene group to form a novel dibenzo[,]azulene ring through a formal [5 + 2] cycloaddition process was first observed. On the other hand, DABCO-promoted reaction of the isocyanides with two molecules of 2-arylidene-1,3-indanediones in acetonitrile at 80 °C afforded functionalized spiro[cyclopenta[]-indene-2,2'-indene] derivatives.

Novel biotin-linked amphiphilic calix[4]arene-based supramolecular micelles as doxorubicin carriers for boosted anticancer activity.

Supramolecular carrier-mediated chemotherapy is a highly attractive strategy for targeted drug delivery. In this study, four novel biotin-linked calix[4]arenes BPCA1-BPCA4 have been rationally designed to construct nano-complex with doxorubicin. The and assessments reveal that BPCA4-DOX with excellent stability are capable of affording significantly superior anti-tumor activity and lower side effects.

Emissive Nanoparticles from Co-assembly of Metallatetragon and Amphiphilic Tetraphenylethylene for Cancer Theranostics.

Platinum(II)-based metallacycles/cages have obtained tremendous attention due to their fascinating topology and wide range of applications, such as fluorescent materials, cell imaging, and tumor treatment. In this work, a metallatetragon () was constructed from 4-(4-(1,2,2-triphenylvinyl)phenyl)pyridine () and 90° -Pt(II) () in acetone through the strategy called "coordination driven self-assembly". Interestingly, through co-assembly of and poly(ethylene glycol)-modified tetraphenylethylene (), fluorescent nanotheranostics, which could generate singlet oxygen (O) under the NIR irradiation and release Pt drugs under a low-pH microenvironment, were prepared successfully.

Selective construction of dispiro[indoline-3,2'-quinoline-3',3''-indoline] and dispiro[indoline-3,2'-pyrrole-3',3''-indoline] via three-component reaction.

A convenient synthetic procedure for the construction of novel dispirooxindole motifs was successfully developed by base-promoted three-component reaction of ammonium acetate, isatins and in situ-generated 3-isatyl-1,4-dicarbonyl compounds. The piperidine-promoted three-component reaction of ammonium acetate, isatins and the in situ-generated dimedone adducts of 3-ethoxycarbonylmethyleneoxindoles afforded mutlifunctionalized dispiro[indoline-3,2'-quinoline-3',3''-indoline] derivatives in good yields and with high diastereoselectivity. On the other hand, a similar reaction of the dimedone adducts of 3-phenacylideneoxindoles afforded unique dispiro[indoline-3,2'-pyrrole-3',3''-indoline] derivatives with a cyclohexanedione substituent.

Convenient Synthetic Protocols for Diverse Functionalized Dihydrobenzofuran-Fused Spiro-indanedione-oxindole Scaffolds.

Diverse functionalized dihydrobenzofuran spiro-indanedione-oxindole scaffolds were conveniently synthesized by base-promoted cyclization reaction of Morita-Baylis-Hillman (MBH) carbonates of isatins and 2-(-hydroxybenzylidene)-1,3-indanediones. The two diastereomeric dispiro[indene-2,1'-cyclopenta[]benzofuran-2',3″'-indolines] could be selectively synthesized by using DABCO or DMAP as a base promoter. More importantly, DABCO or DMAP facilitated the annulation reaction of MBH formates of isatins and 2-(-hydroxybenzylidene)-1,3-indanediones selectively, resulting in spiro[cyclopropa[]chromene-1,2'-indene]-1',3'-diones or dispiro[indene-2,1'-cyclopenta[]benzofuran-2',3″'-indolines].

Tandem ring-opening and formal [3 + 2] cycloaddition of furo[2,3-]pyrimidine-2,4-diones.

The base promoted tandem annulation reaction of activated cyclic 1,3-dipolarophiles such as 2-arylidene-1,3-indanediones, 2-(-hydroxybenzylidene)-1,3-indanediones and 3-methyleneoxindoles with functionalized furo[2,3-]pyrimidine-2,4-diones was systematically investigated. This reaction provided efficient synthetic protocols for complex dispiro/dispiro fused tricyclic compounds including dispiro[indene-2,3'-cyclopentane-1',5''-pyrimidines], dispiro[indoline-3,3'-cyclopentane-1',5''-pyrimidines] and spiro[cyclopenta[]indeno[1,2-]chromene-3,5'-pyrimidines] in good yields and with high diastereoselectivity. The reaction was believed to proceed sequential ring-opening of the furyl ring, formal [3 + 2] cycloaddition and annulation of the -hydroxyphenyl group.

The unique reactivity of 5,6-unsubstituted 1,4-dihydropyridine in the Huisgen 1,4-diploar cycloaddition and formal [2 + 2] cycloaddition.

The three-component reaction of isoquinolines, dialkyl acetylenedicarboxylates, and 5,6-unsubstituted 1,4-dihydropyridines in acetonitrile at room temperature afforded functionalized isoquinolino[1,2-][1,6]naphthyridines in good yields and with high diastereoselectivity. More importantly, the formal [2 + 2] cycloaddition reaction of dialkyl acetylenedicarboxylates and 5,6-unsubstituted 1,4-dihydropyridines in refluxing acetonitrile gave unique 2-azabicyclo[4.2.

Pd/Cu-catalyzed cascade Heck-type reactions of alkenyl halides with terminal alkynes toward substituted pyrrolidine analogues.

Pd/Cu-catalyzed cascade Heck-type reactions of alkenyl halides with terminal alkynes have been developed. This research provides an efficient atom-economical approach to access a variety of highly substituted pyrrolidines in moderate to good yields. This protocol features readily available substrates, broad substrate scope, easy scale-up, high selectivities and versatile transformations.

Synthesis of Multisubstituted Allenes by Palladium-Catalyzed Carboetherification of β,γ-Unsaturated Ketoximes with Propargylic Acetates.

A highly efficient Pd-catalyzed carboetherification reaction of β,γ-unsaturated ketoximes with propargylic acetates is demonstrated. This method provides a practical protocol for accessing the incorporation of an allene moiety into 3,5-disubstituted and 3,5,5-trisubstituted isoxazolines. The salient features of this transformation include a broad substrate scope, good functional group tolerance, an easy scale-up, versatile transformations, and applications in the late-stage modification of drugs.

Pillar[5]arene-Derived Terpyridinepalladium(II) Complex: Synthesis, Characterization, and Application in Green Catalysis.

Metal nanoparticle catalysts have attracted great interest because they possess high surface-to-volume ratios and exhibit a very large number of catalytically active sites per unit area. However, high surface-to-volume ratios will induce nanoparticle aggregates during the catalytic reactions, making them lose their catalytic activity. In this work, a monoterpyridine-unit-functionalized pillar[5]arene (TP5) was synthesized successfully, which can be used as anchoring sites for the controllable preparation of well-dispersed palladium nanoparticles [TP5/Pd(0) NPs].

Acid-Modulated Construction of Cyclopenta[]indole and Cyclohepta[]indole via Unprecedented C3/C2 Carbocation Rearrangement.

-TsOH-catalyzed cycloaddition of various 3-vinylindoles and (indol-2-yl)diphenylmethanols in acetonitrile gave the functionalized cyclopenta[]indoles in good yields and with high diastereoselectivity via [3 + 2] cycloaddition reaction. More importantly, FeCl-catalyzed annulation reaction afforded unexpected functionalized cyclohepta[1,2-:4,5-']diindoles in satisfactory yields, in which a formal [4 + 3] cycloaddition and an unprecedented C3/C2 carbocation rearrangement were first confirmed by the determination of single-crystal structure.