Palladium-catalyzed C-C bond cleavage of N-cyclopropyl acylhydrazones.

Despite their utility as directing groups, the C-C bond cleavage of cyclopropanes utilizing hydrazones has not been explored. Herein, Pd-catalyzed C-C bond cleavage reaction of N-cyclopropyl acylhydrazones, followed by cycloisomerization to yield pyrazoles, has been developed. The protocol enables the synthesis of various α-pyrazole carbonyl compounds, which have a potential of biological activity. Control experiments and DFT calculations suggest that ß-carbon elimination of a stable 6-membered chelate palladium complex occurs, generating a conjugated azine as a reaction intermediate for the following cycloisomerization.

P(III)-Mediated Formal Reductive N-H Bond Insertion Reaction of Hydrazones to α-Keto Esters.

A diazo-, metal-, and base-free multi-substituted hydrazone synthesis via a formal reductive N-H bond insertion reactions of hydrazones to α-keto esters has been developed. The protocol features a broad substrate scope and good functional group tolerance, providing N-H bond insertion products in moderate to excellent yields. Moreover, P(III)-mediated N-H functionalization of pharmaceutical containing hydrazone moiety was also successfully achieved.

Synthesis of Spiro[indole-3,3'-pyrrolidine]-2'-(thi)ones.

Spiro[indole-3,3'-pyrrolidine]-2'-ones were synthesized via one-pot chloroformylation-dearomatizing spirocyclization of tryptamine derivatives. Moreover, the "thio" equivalent spiro[indole-3,3'-pyrrolidine]-2'-thiones, for which the synthesis and properties were previously unreported, were synthesized. The procedures are easily implemented, have a broad scope, and are transition-metal-free and cheap. To demonstrate the utility of the synthetic methodology, the spiro[indole-3,3'-pyrrolidine]-2'-ones were converted into heterocyclic scaffolds, such as an optically active spiroindoline and spirooxindole.

Synthesis of isolable ß-chloroenamines from N-alkoxylactams with organometallic reagents.

An efficient approach to access isolable ß-chloroenamines via nucleophilic addition/dehydration of α-chloro N-alkoxylactam with organolithium and Grignard reagents is reported. This approach is amenable to the synthesis of ß-chloroenamines by incorporating various C(sp) and C(sp2) units, such as alkyne, aryl, and heteroaryl moieties. The sequential reaction has a broad substrate scope and can be carried out for a scalable synthesis of ß-chloroenamines. Control experiments suggested that both chloro and alkoxy groups act as inductive electron-withdrawing substituents to improve the stability of the enamines.

Copper-Catalyzed Aerobic C(sp3)-H Oxidation of ß-(Alkoxy)imino Carbonyl Compounds.

Direct oxidation of the C(sp3)-H bond of ß-(alkoxy)imino carbonyl compounds using copper acetate and molecular oxygen has been established. The protocol features a broad substrate scope and generates 1-imino-2,3-dicarbonyls in good to excellent yields.

Synthesis, Structure, and Characterization of Thiacalix[4]-2,8-thianthrene.

Sulfur-containing macrocycles have attracted substantial interest because they exhibit unique characteristics due to their polygonal ring-shaped skeleton. In this study, a thianthrene-based cyclic tetramer with the sulfur linker, thiacalix[4]-2,8-thianthrene (TC[4]TT), was successfully prepared from a cyclo-p-phenylenesulfide derivative using acid-induced intramolecular condensation. Single crystal X-ray diffraction revealed that TC[4]TT adopts an alternative octagonal form recessed to the inner side. Its internal cavity included small solvents, such as chloroform and carbon disulfide. Due to its polygonal geometry, TC[4]TT laminated in a honeycomb-like pattern with a porous channel. Furthermore, TC[4]TT showed fluorescence and phosphorescence emission in a CH2Cl2 solution at ambient and liquid nitrogen temperatures. Both emission bands were slightly redshifted compared with those of the reference compounds (di(thanthren-2-yl)sulfane (TT2S) and thianthrene (TT)). This work describes a sulfur-containing thiacalixheterocycle-based macrocyclic system with intriguing supramolecular chemistry based on molecular tiling and photophysical properties in solution.

Construction of pyrazolodiazepines using AuI, a dual functional gold catalyst.

N,N'-5,7-Fused compounds are important molecules exhibiting medicinal potential. Herein, we report a practical and robust method for synthesising pyrazolodiazepines from N-piperidinyl alkynylhydrazides using a AuI catalyst. The broad substrate scope of alkynylhydrazides and synthetic application of pyrazolodiazepines are demonstrated. In addition, control experiments provide detailed information on the reaction mechanism, in which AuI promotes both the sequential intramolecular nucleophilic addition and the double nucleophilic substitution reaction as a π-acidic and nucleophilic dual functional catalyst.

Janus-Type AIE Fluorophores: Synthesis and Properties of π-Extended Coumarin-Bearing Triskelions.

Janus-type triskelion-shaped fluorophores comprising coumarins bearing various electron-donating substituents (1aad, 1add, 1ccd, and 1cdd) were successfully synthesized via an intramolecular Ullmann coupling. Density functional theory (DFT) calculations indicated that all the compounds presented two different molecular surfaces, similar to Janus-type molecules. The absorption and fluorescence spectra of asymmetrical derivatives 1aad, 1add, 1ccd, and 1cdd exhibited a bathochromic shift due to their narrow highest occupied molecular orbital (HOMO) -lowest unoccupied molecular orbital (LUMO) gap. Natural transition orbital (NTO) analysis indicated that the excited state orbital overlaps differ among the C3 symmetrical and asymmetrical dyes. These triskelion-shaped fluorophores were found to form molecular nanoaggregates in THF/H2O mixtures and demonstrated aggregation-induced emission (AIE) enhancement characteristics as a result of restricting their molecular inversion. These results indicate that Janus-type AIE fluorophores are potentially applicable as solid-state fluorescent chiral materials, which can be optimized by controlling their molecular rearrangement in the solid state.

Sc(OTf)3-Catalyzed Iodocyclization/Ritter-Type Amidation of N-Alkoxypropiolamides: A Synthetic Strategy for Isoxazol-3(2H)-ones.

A Sc(OTf)3-catalyzed iodocyclization/Ritter-type amidation of N-alkoxypropiolamides for the synthesis of 4-iodoisoxazol-3(2H)-ones bearing an amide group has been developed. This domino protocol allows the construction of a valuable heterocycle, isoxazol-3(2H)-one, as well as the introduction of two functional groups. The reaction has a broad substrate scope and can be carried out on a large scale. Control experiments suggest that Sc(OTf)3 acts as a dual activator for both the iodocyclization and amidation steps. In addition, the N-alkoxy group in the substrate suppresses some of the side reactions.

γ-C (sp3)-H bond functionalisation of α,ß-unsaturated amides through an umpolung strategy.

The nucleophilic γ-phenylation and γ-alkylation of α,ß-unsaturated amides have been developed. This umpolung reaction allows the regioselective introduction of phenyl and alkyl groups to a vinylketene N,O-acetal, which is generated in situ from an α,ß-unsaturated N-alkoxyamide, followed by N-O bond cleavage in a two-step, one-pot process.

Hydration of Polycationic [5]Radialene with Quintuple 1,3-Dithiol-2-ylidenes Leads to a New Class of π-Extended Tetrathiafulvalene Scaffold.

[5]Radialene with quintuple 4,5-benzo-1,3-dithiol-2-ylidenes (DTs) easily forms a stable polycationic salt (1)4+ (BF4 - )4 owing to its aromatic character in the central cyclopentadienide ring. In this work, it was found that the polycationic salt (1)4+ underwent a hydration reaction in moist polar solvent to give several unexpected products, namely, an oxygen adduct dicationic salt (2)2+ , a tetrathiafulvalene (TTF) vinylogue (3) with 1,4-dithiine-2(3H)-one moieties, and an oxygen adduct of π-extended TTF with a cyclopentenone core (4). Their molecular structures were fully determined by X-ray crystal-structure analysis. In this reaction, irreversible hydration to the polycationic salt might either initiate the ring expansion and lead to the successive hydration at the specific cationic DT ring (for 3), or promote the transannular reactions to the next DT ring followed by elimination of the DT ring (for 4). Cyclic voltammetry and differential pulse voltammetry measurements for compound 3 indicated the occurrence of multi redox process resulting from electronic delocalization on the vinylogous TTF moiety. The electronic structures of the cationic species of 3 were also investigated by electronic spectra.

Copper-Catalyzed Cycloisomerization of Cyclopropenylimine for Synthesis of Pyrroles.

Copper-catalyzed cycloisomerization of 3-iminocyclopropenes for synthesis of pyrroles has been developed. The reaction allows regioselective construction of pyrroles with various substitution patterns, including fully substituted pyrroles. The method was successfully applied to synthesis of steroidal pyrroles as well as a N-fused pyrrole.

Chiral isoxazolidine-mediated stereoselective umpolung α-phenylation of methyl ketones.

An effective asymmetric α-phenylation of methyl ketones with triphenylaluminium in the presence of (+)-benzopyranoisoxazolidine has been developed. The reaction proceeds via the in situ formation of a chiral N-alkoxyenamine and the subsequent diastereoselective nucleophilic phenylation to provide α-phenylated products in moderate to good yields, with high enantioselectivities.

Stepwise Growth of Fullerene Nanoparticles through Guest Exchange of γ-Cyclodextrin Complexes in Water.

Stepwise growth of fullerene nanoparticles (nCx ; x=60 or 70) was performed through guest exchange of a γ-cyclodextrin (γ-CD) complex. Fullerenes bicapped by γ-CD were mixed with presynthesized nCx in the presence of poly(ethylene glycol) (PEG) in water. Fullerenes expelled from the γ-CD hosts by PEG were piled on the original nCx , resulting in growth of nCx . This process could be repeated and the size of nCx increased according to the number of growth steps. The growth of fullerene nanoparticles was confirmed by UV/Vis absorption spectroscopy, dynamic light scattering measurements, and TEM observations. The stepwise growth method also enabled the preparation of C60 /C70 core/shell fullerene nanoparticles, which had the ability to photogenerate active oxygen, 1 O2 .

Reversible Vesicle-to-Disk Transitions of Liposomes Induced by the Self-Assembly of Water-Soluble Porphyrins.

Structural control of lipid membranes is important for mechanisms underlying biological functions and for creating high-functionality soft materials. We demonstrate the reversible control of vesicle structures (liposomes) using supramolecular assemblies. Specifically, water-soluble anionic porphyrin molecules interact with positively charged lipid membrane surfaces to form one-dimensional self-assembled structures (J-aggregates) under acidic conditions. Cryogenic transmission electron microscopy revealed that porphyrin J-aggregates on the membrane surface induced an extensive structural change from vesicles to layered disks. Neutralization of the solution deformed the porphyrin J-aggregates, thereby reforming nanosized liposomes from the layered disks.

Incorporation of large guest molecules into liposomes via chemical reactions in lipid membranes.

The incorporation of hydrophobic guest molecules into lipid membranes by the exchange of the guest molecule from a cyclodextrin (CDx) complex to a liposome is limited to guest molecules that can be included in CDxs. To solve this problem, large guest molecules were incorporated into liposomes by chemical reactions of guest molecules in lipid membranes. Stable lipid-membrane-incorporated fullerene derivatives with large substituent(s) were prepared by Diels-Alder reactions in lipid membranes.

Lipid-membrane-incorporated arylboronate esters as agents for boron neutron capture therapy.

Arylboronate esters bearing methyl groups in both of their ortho positions were stably incorporated into lipid membranes at high concentrations without undergoing hydrolysis to the corresponding boronic acids. This method could be used in combination with previous methods to increase the maximum ratio of boron atoms in liposomal boron carriers.

Nucleophilic Arylation of N,O-Ketene Acetals with Triaryl Aluminum Reagents: Access to α-Aryl Amides through an Umpolung Process.

A novel approach for the umpolung α-arylation of amides is presented. By the nucleophilic phenylation of O-silyl N,O-ketene acetals, generated in situ from N-alkoxy amides, a phenyl group can be introduced onto the α-carbon atom of amides through N-O bond cleavage in a two-step, one-pot process. The asymmetric synthesis of α-aryl amides through the diastereoselective arylation of a chiral N,O-ketene acetal is also described.

Gold-Catalyzed [3+2]/Retro-[3+2]/[3+2] Cycloaddition Cascade Reaction of N-Alkoxyazomethine Ylides.

A novel cascade reaction has been developed for the synthesis of 2,6-methanopyrrolo[1,2-b]isoxazoles based on the gold-catalyzed generation of an N-allyloxyazomethine ylide. This reaction involves sequential [3+2]/retro-[3+2]/[3+2] cycloaddition reactions, thus providing facile access to fused and bridged heterocycles which would be otherwise difficult to prepare using existing synthetic methods. Notably, this reaction allows the efficient construction of three C-C bonds, one C-O bond, one C-N bond and one C-H bond, as well as the cleavage of one C-C bond, one C-O bond and one C-H bond in a single operation. The intermolecular cycloaddition of an N-allyloxyazomethine ylide and the subsequent application of the product to the synthesis of tropenol is also described.

tert-Butyl Iodide Mediated Reductive Fischer Indolization of Conjugated Hydrazones.

A novel reductive Fischer indolization of readily available N-aryl conjugated hydrazones with tert-butyl iodide has been developed. In this reaction, tert-butyl iodide is used as anhydrous HI source, and the generated HI acts as a Brønsted acid and a reducing agent. This operationally simple method allows access to various indole derivatives. Furthermore, the procedure can be applied to the synthesis of biologically active compounds.