Palladium-Catalyzed C-H Arylation of [1,1'-Biphenyl]-2-ols with Chloroarenes.

Palladium-catalyzed, hydroxy-group-directed C-H arylation of [1,1'-biphenyl]-2-ols with chloroarenes was performed. The reaction showed a broad substrate scope and was successfully applied to pharmaceuticals containing a chloro group. Using 2-heteroarylphenols instead of [1,1'-biphenyl]-2-ols also yielded the desired products. The arylated product was further transformed into a triphenylene derivative.

A Highly Conductive n-Type Coordination Complex with Thieno[3,2-b]thiophene Units: Facile Synthesis, Orientation, and Thermoelectric Properties.

An organometallic nickel complex containing thieno[3,2-b]thiophene units was designed and synthesized. Composite films of the resulting nickel complex and polyvinylidene difluoride, which can be fabricated via a simple solution process under atmospheric conditions, exhibit remarkably high n-type conductivity (>200 S cm-1). Moreover, the thermoelectric power factor of the n-type composite film was proven to be air stable. A grazing-incidence wide-angle X-ray diffraction analysis indicated a significant impact of introducing the thieno[3,2-b]thiophene core into the backbone of the nickel complex on the orientation within the composite films.

Direct C3-Selective Arylation of N-Unsubstituted Indoles with Aryl Chlorides, Triflates, and Nonaflates Using a Palladium-Dihydroxyterphenylphosphine Catalyst.

A palladium-dihydroxyterphenylphosphine (DHTP) catalyst was successfully applied to the direct C3-arylation of N-unsubstituted indoles with aryl chlorides, triflates, and nonaflates. This catalyst showed C3-selectivity, whereas catalysts with other structurally related ligands exhibited N1-selectivity. Complex formation between the lithium salts of the ligand and the indole is assumed to accelerate the arylation at the C3 position. Reactions using 3-alkylindoles afforded 3,3-disubstituted indolenines, which can be further converted to the corresponding indoline derivatives.

Palladium-Catalyzed External-CO-Free Carbonylation of Aryl Bromides Using 2,4,6-Trichlorophenyl Formate.

A practical Pd-catalyzed carbonylation of (hetero)aryl bromides using a crystalline carbon monoxide (CO) surrogate, 2,4,6-trichlorophenyl formate (TCPF), was developed. This reaction proceeds without the slow addition technique that was previously required and with a low catalyst loading (1 mol%). The utility of this Pd-catalyzed external-CO-free carbonylation using TCPF was demonstrated in the synthesis of a histone deacetylase inhibitor.

Three-step synthesis of 2,5,7-trisubstituted indoles from N-acetyl-2,4,6-trichloroaniline using Pd-catalyzed site-selective cross-coupling.

We report a facile three-step synthesis of 2,5,7-trisubstituted indoles from N-acetyl-2,4,6-trichloroaniline, with the first step featuring Pd/dihydroxyterphenylphosphine (DHTP)-catalyzed ortho-selective Sonogashira coupling followed by cyclization to afford 2-substituted 5,7-dichloroindoles. Subsequent introduction of aryl or alkenyl groups at the C7 position was achieved by Pd/DHTP-catalyzed site-selective Kumada-Tamao-Corriu coupling, with further substitution of the chlorine at the C5 position (Suzuki-Miyaura coupling or Buchwald-Hartwig amination) affording 2,5,7-trisubstituted indoles.

Ligand-Controlled Site-Selective Cross-Coupling.

Site-selective mono-cross-coupling reactions involving dichloro- or dibromo(hetero)aryl substrates are utilized to prepare substituted monochloro- or monobromo(hetero)arenes, which are used as drug components and synthetic precursors. In these reactions, selectivity toward the preferred reaction site of a dihalo(hetero)arene can vary depending on the ancillary ligand of the transition metal catalyst. This review summarizes the examples of ligand-controlled site-selective cross-coupling reactions, specifically those mediated by Pd complexes.

One-Pot Synthesis of Substituted Benzo[b]furans and Indoles from Dichlorophenols/Dichloroanilines Using a Palladium-Dihydroxyterphenylphosphine Catalyst.

Disubstituted benzo[b]furans were synthesized by ortho-selective Sonogashira coupling of dichlorophenols and terminal alkynes, followed by cyclization and Suzuki-Miyaura coupling in one pot, using a palladium-dihydroxyterphenylphosphine (Cy-DHTP) catalyst. The use of substoichiometric amounts of tetrabutylammonium chloride was effective in accelerating the Suzuki-Miyaura coupling. This protocol was also successfully applied to the one-pot synthesis of disubstituted indoles from dichloroaniline derivatives.

Three-Step Synthesis of Fluoranthenes through Pd-Catalyzed Inter- and Intramolecular C-H Arylation.

A three-step synthetic method for the preparation of fluoranthenes, involving Miura's intermolecular C-H arylation, nonaflation, and intramolecular C-H arylation, has been developed. Various 1-naphthols and haloarenes were successfully used as substrates. Reaction conditions that afford high site selectivity have been developed for the intramolecular C-H arylation step.

Practical Synthesis of Axially Chiral Dicarboxylates via Pd-Catalyzed External-CO-Free Carbonylation.

We have developed a safe and practical synthetic method for preparing axially chiral diphenyl dicarboxylates using Pd-catalyzed external-CO-free carbonylation with phenyl formate as a CO surrogate. Optimized conditions consisted of axially chiral [1,1'-binaphthalene]-2,2'-diyl ditriflate and its congeners, each easily prepared from commercially available enantiomerically pure diols, Pd(OAc)2, 1,3-bis(diphenylphosphino)propane, ethyldiisopropylamine, and no solvent. To demonstrate the potential utility of these products, this method was conducted on gram-scale and the phenyl ester products were converted to other useful compounds, and both processes were carried out without difficulty.

One-pot synthesis of substituted benzo[b]furans from mono- and dichlorophenols using palladium catalysts bearing dihydroxyterphenylphosphine.

A dihydroxyterphenylphosphine bearing cyclohexyl groups on the phosphorus atom (Cy-DHTP) was found to be a powerful ligand for the palladium-catalyzed one-pot synthesis of substituted benzo[b]furans from 2-chlorophenols and terminal alkynes. This catalyst system was also applicable to the sequential one-pot synthesis of disubstituted benzo[b]furans from dichlorophenols via the Suzuki-Miyaura cross-coupling of chlorobenzo[b]furan with boronic acids. The use of two ligands, Cy-DHTP and XPhos, is the key to promoting the reactions. Mechanistic studies suggest that the Pd-Cy-DHTP catalyst is the active species in the Sonogashira cross-coupling step, while the Pd-XPhos catalyst accelerates the Suzuki-Miyaura cross-coupling step.

Repetitive two-step method for o,o,p- and o,p-oligophenylene synthesis through Pd-catalyzed cross-coupling of hydroxyterphenylboronic acid.

A repetitive two-step method involving the Pd-catalyzed Suzuki-Miyaura coupling of hydroxyterphenylboronic acid and the subsequent nonaflation of the hydroxy group has been developed for the synthesis of oligophenylenes. This method readily afforded o,o,p- and o,p-oligophenylenes with defined chain lengths. X-ray crystallography was employed to obtain the structure of the o,p-oligophenylene 9-mer.

Pyrroloindoline/Pyridoindoline Synthesis via C3-Dearomative Arylation/Cyclization of Tryptamine/Homotryptamine Derivatives Using Palladium-Dihydroxyterphenylphosphine Catalyst.

A palladium-dihydroxyterphenylphosphine (DHTP) catalyst was successfully applied to the dearomative C3-arylation of tryptamine derivatives with aryl nonaflates. The intramolecular cyclization of the resulting 3,3-disubstituted indolenines afforded C3a-arylated pyrroloindolines in one pot. We postulate that the formation of complexes between the lithium salts of DHTP and the tryptamine derivative is the key to promoting selective arylation at the C3-position of the indole ring. Furthermore, reactions using homotryptamine derivatives successfully provided C4a-arylated pyridoindolines.

Synthesis of Symmetrical Sulfides Enabled by a Sulfur Dioxide Surrogate Acting as a Divalent Sulfur Source.

Herein, we present a safe and practical methodology for synthesizing symmetrical sulfides using iodoarenes and potassium metabisulfite (K2S2O5). While K2S2O5 is known as a convenient sulfur dioxide surrogate, here it acts as a divalent sulfur source, pioneering its potential utility. The reaction exhibits wide substrate generality in which even highly bulky substrates can be applied to afford sterically congested sulfides.

Chiral Silica with Preferred-Handed Helical Structure via Chiral Transfer.

A strategy to obtain chiral silica using an achiral stereoregular polymer with polyhedral oligomeric silsesquioxane (POSS) side chains is described herein. The preferred helical conformation of the POSS-containing polymer could be achieved by mixing isotactic polymethacrylate-functionalized POSS (it-PMAPOSS) and a chiral dopant. The array structure of POSS molecules, which are placed along the helical conformation, is memorized even after removing the chiral dopant at high temperatures, leading to a chiral silica compound with exclusive optical activity after calcination.

Hydroxyterphenylphoshine-palladium catalyst for benzo[b]furan synthesis from 2-chlorophenols. bifunctional ligand strategy for cross-coupling of chloroarenes.

A catalyst composed of Pd and hydroxyterphenylphosphine was found to be effective for one-pot benzo[b]furan synthesis from 2-chlorophenols and alkynes.

Site-selective cross-coupling of dichlorinated benzo-fused nitrogen-heterocycles with Grignard reagents.

Site-selective cross-coupling of dihaloarenes constitutes a useful method for synthesis of multi-substituted arenes. In this paper, we report the site-selective cross-coupling of dichlorinated benzo-fused nitrogen-heterocycles having two chloro groups on the benzene ring. These dichlorinated heterocycles reacted with Grignard reagents in the presence of PdCl(2)(PCy(3))(2) at the positions ortho to the nitrogen-based substituents with high selectivities. A mechanism in which interaction between Lewis acidic Mg and Cl of the ortho position facilitates C-Cl bond cleavage is proposed.

Discovery of a Potent Anticancer Agent PVHD303 with in Vivo Activity.

As a part of our continuous structure-activity relationship (SAR) studies on 1-(quinazolin-4-yl)-1-(4-methoxyphenyl)ethan-1-ols, the synthesis of derivatives and their cytotoxicity against the human lung cancer cell line A549 were explored. This led to the discovery of 1-(2-(furan-3-yl)quinazolin-4-yl)-1-(4-methoxyphenyl)ethan-1-ol (PVHD303) with potent antiproliferative activity. PVHD303 disturbed microtubule formation at the centrosomes and inhibited the growth of tumors dose-dependently in the HCT116 human colon cancer xenograft model in vivo.

Synthesis of 2,2,5-Trisubstituted 2H-Pyrroles and 2,3,5-Trisubstituted 1H-Pyrroles by Ligand-Controlled Site-Selective Dearomative C2-Arylation and Direct C3-Arylation.

Palladium-catalyzed site-selective dearomative C2-arylation of 2,5-diaryl-1H-pyrroles with aryl chlorides was accomplished, and a series of 2,2,5-triaryl-2H-pyrroles were synthesized. In addition, the site selectivity of the reaction was switched by simply changing the ligand, and the direct C3-arylated 2,3,5-triaryl-1H-pyrroles were prepared. The obtained 2,2,5-triaryl-2H-pyrroles could be further transformed into 2,2,5,5-tetraarylpyrrolidines.

Histopathological analysis of the differential diagnosis of peripheral odontogenic fibroma from fibrous epulis.

OBJECTIVES: Peripheral odontogenic fibroma (POF) is a relatively rare odontogenic tumor of the gingiva. Although its histological differential diagnosis from fibrous epulis (FE) is important, no study has reported the differences in their expression of immunohistochemical markers. Here, we compared the expression of tumor markers that are frequently used for the differential diagnosis of fibroproliferative lesions between POF and FE. METHODS: Forty cases were selected, including 20 POF and 20 FE cases. CD34, B cell lymphoma (Bcl)-2, and Ki-67 were used as markers for immunohistochemical examination. The positive cell ratio was calculated, and Mann-Whitney U test was performed for statistical analysis. RESULTS: POF and FE were negative for CD34 expression but showed Bcl-2 and Ki-67 expression. The ratio of Bcl-2- and Ki-67-positive cells was significantly higher in POF than in FE (p < 0.001). CONCLUSIONS: POF is CD34 negative, and Bcl-2 and Ki-67 positive-cell ratio differs between POF and FE, suggesting that these proteins may serve as immunohistochemical markers for the differential diagnosis of POF.

Total Synthesis of Termicalcicolanone A via Organocatalysis and Regioselective Claisen Rearrangement.

A total synthesis of an anticancer xanthone natural product termicalcicolanone A utilizing multiple nucleophilic aromatic substitutions and pericyclic reactions has been developed. The pyrano[3,2- b]xanthen-6-one scaffold was constructed via NHC-catalyzed aroylation to produce the benzophenone intermediate, Claisen cyclization to form the pyran ring, and intramolecular 1,4-addition to construct the xanthone framework. The prenyl group was introduced in the final stages of the synthesis through regioselective Claisen rearrangement. The synthesis has been achieved in 19 steps.