N-Arylation of 3-Formylquinolin-2(1H)-ones Using Copper(II)-Catalyzed Chan–Lam Coupling

3-formyl-2-quinolones have attracted the scientific community’s attention because they are used as versatile building blocks in the synthesis of more complex compounds showing different and attractive biological activities. Using copper-catalyzed Chan–Lam coupling, we synthesized 32 new N-aryl-3-formyl-2-quinolone derivatives at 80 °C, in air and using inexpensive phenylboronic acids as arylating agents. 3-formyl-2-quinolones and substituted 3-formyl-2-quinolones can act as substrates, and among the products, the p-methyl derivative 9a was used as a substrate to obtain different derivatives such as alcohol, amine, nitrile, and chalcone.     

A mild and efficient copper-catalyzed N-arylation of unprotected sulfonimidamides using boronic acids

An efficient and low cost copper catalyzed system for N-arylation of sulfonimidamides has been developed. The reaction proceeds at room temperature under base free conditions. Various N-aryl, N-heteroaryl, and N-cyclopropyl sulfonimidamides were obtained in good to excellent yields.     

Copper(I) 3-Methylsalicylate Mediates the Chan–Lam N-Arylation of Heterocycles

Copper(I) 3-methylsalicylate (CuMeSal) mediates N-arylation reactions between aryl boronic acids and aromatic heterocycles (Chan–Lam coupling) under moderate reaction conditions (K₂CO₃, methanol, 65 °C, in air, 3–5 h). Both electron-rich and electron-deficient aryl boronic acids and a diverse set of N-heterocycles were allowed to react and gave N-arylation products in reasonable yields, which demonstrate the utility of this catalyst.     

Microwave‐promoted piperidination of halopyridines: a comparison between Ullmann,Buchwald–Hartwig and uncatalysed SNAr reactions

A comparative study between the most used methodologies for the preparation of piperidinyl pyridines (Buchwald–Hartwig reaction, Ullmann reaction and nucleophilic aromatic substitution (S_NAr)) by microwave‐assisted piperidination of halopyridines is reported. Our results suggest that the Ullmann reaction is most effective for less reactive halopyridines, while uncatalysed S_NAr is sufficient for more reactive ones. Copyright © 2012 John Wiley & Sons, Ltd.     

Highly regioselective synthesis of chiral diamines via a Buchwald–Hartwig amination from camphoric acid and their application in the Henry reaction

In this work the synthesis of new asymmetric diamine ligands from camphoric acid is described. The new diamines can be directly prepared in a regioselective arylation of the less hindered primary amine group of (+)‐cis‐1,2,2‐trimethylcyclopentane‐1,3‐diamine via a Buchwald–Hartwig amination in high yields. The resulting diamines incorporate a secondary and primary amine group and were successfully applied as ligands in a copper‐catalyzed Henry reaction. Copyright © 2014 John Wiley & Sons, Ltd.     

Synthesis of Novel Methyl 7-[(Hetero)arylamino]thieno[2,3-b]pyrazine-6-carboxylates and Antitumor Activity Evaluation: Effects in Human Tumor Cells Growth,Cell Cycle Analysis,Apoptosis and Toxicity in Non-Tumor Cells

Several novel methyl 7-[(hetero)arylamino]thieno[2,3-b]pyrazine-6-carboxylates were synthesized by Pd-catalyzed C–N Buchwald–Hartwig cross-coupling of either methyl 7-aminothieno[3,2-b]pyrazine-6-carboxylate with (hetero)arylhalides or 7-bromothieno[2,3-b]pyrazine-6-carboxylate with (hetero)arylamines in good-to-excellent yields (50% quantitative yield), using different reaction conditions, namely ligands and solvents, due to the different electronic character of the substrates. The antitumoral potential of these compounds was evaluated in four human tumor cell lines: gastric adenocarcinoma (AGS), colorectal adenocarcinoma (CaCo-2), breast carcinoma (MCF7), and non-small-cell lung carcinoma (NCI-H460) using the SRB assay, and it was possible to establish some structure–activity relationships. Furthermore, they did not show relevant toxicity against a non-tumor cell line culture from the African green monkey kidney (Vero). The most promising compounds (GI₅₀ ≤ 11 µM), showed some selectivity either against AGS or CaCo-2 cell lines without toxicity at their GI₅₀ values. The effects of the methoxylated compounds 2b (2-OMeC₆H₄), 2f and 2g (3,4- or 3,5-diOMeC₆H₃, respectively) on the cell cycle profile and induction of apoptosis were further studied in the AGS cell line. Nevertheless, even for the most active (GI₅₀ = 7.8 µM) and selective compound (2g) against this cell line, it was observed that a huge number of dead cells gave rise to an atypical distribution on the cell cycle profile and that these cells were not apoptotic, which points to a different mechanism of action for the AGS cell growth inhibition.     

Nickel‐catalyzed Buchwald–Hartwig amination of pyrimidin‐2‐yl tosylates with indole,benzimidazole and 1,2,4‐triazole

Nickel‐catalyzed Buchwald–Hartwig amination of pyrimidin‐2‐yl tosylates with indole and benzimidazole was achieved using Ni(dppp)Cl₂ as catalyst, yielding a variety of novel C2‐substituted pyrimidine derivatives in good yields. This reaction proved to be tolerant of various pyrimidin‐2‐yl tosylates bearing either electron‐donating or electron‐withdrawing groups as well as nucleophiles including indole, benzimidazole and 1,2,4‐triazole. Copyright © 2016 John Wiley & Sons, Ltd.     

Carbene adduct of cyclopalladated ferrocenylimine‐assisted synthesis of aminopyridine derivatives by the amination of chloropyridines with primary and secondary amines

An efficient, simple way to synthesize aminopyridine derivatives is presented, based on Buchwald–Hartwig aminations. Using 1 mol% N‐heterocyclic carbene adduct of cyclopalladated ferrocenylimine in the presence of 1.5 equiv. ^tBuOK as base in dioxane at 110°C offered moderate to excellent yields in the reaction of chloropyridines with primary and secondary amines, including sterically hindered amines and alkyl amines.     

1, 1'-Binaphthyl-2, 2'-diamine Dihydrochloride: an Efficient Ligand for the N-Arylation of Imidazole with Aryl/heteroaryl Halides Catalyzed by CuI

Employing 1,1'-binaphthyl-2,2'-diamine(BINAM) dihydrochloride as an efficient and commercially available ligand, relatively mild and highly efficient copper-catalyzed coupling reactions of imidazole with aryl and heteroaryl halides have been developed. Various N-arylimidazoles could be synthesized in moderate to excellent yields.     

Transamidation of Amides and Amidation of Esters by Selective N–C(O)/O–C(O) Cleavage Mediated by Air- and Moisture-Stable Half-Sandwich Nickel(II)–NHC Complexes

The formation of amide bonds represents one of the most fundamental processes in organic synthesis. Transition-metal-catalyzed activation of acyclic twisted amides has emerged as an increasingly powerful platform in synthesis. Herein, we report the transamidation of N-activated twisted amides by selective N–C(O) cleavage mediated by air- and moisture-stable half-sandwich Ni(II)–NHC (NHC = N-heterocyclic carbenes) complexes. We demonstrate that the readily available cyclopentadienyl complex, [CpNi(IPr)Cl] (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene), promotes highly selective transamidation of the N–C(O) bond in twisted N-Boc amides with non-nucleophilic anilines. The reaction provides access to secondary anilides via the non-conventional amide bond-forming pathway. Furthermore, the amidation of activated phenolic and unactivated methyl esters mediated by [CpNi(IPr)Cl] is reported. This study sets the stage for the broad utilization of well-defined, air- and moisture-stable Ni(II)–NHC complexes in catalytic amide bond-forming protocols by unconventional C(acyl)–N and C(acyl)–O bond cleavage reactions.     

Rational Design of Push–Pull Fluorene Dyes: Synthesis and Structure–Photophysics Relationship

Our work surveyed experimental and theoretical investigations to construct highly emissive D –π–A (D=donor, A=acceptor) fluorenes. The synthetic routes were optimised to be concise and gram‐scalable. The molecular design was first rationalised by varying the electron‐withdrawing group from an aldehyde, ketotriazole or succinyl to methylenemalonitrile or benzothiadiazole. The electron‐donating group was next varied from aliphatic or aromatic amines to saturated cyclic amines ranging from aziridine to azepane. Spectroscopic studies correlated with TD‐DFT calculations provided the optimised structures. The selected push–pull dyes exhibited visible absorptions, significant brightness, important solvatofluorochromism, mega‐Stokes shifts (>250 nm) and dramatic shifts in emission to the near‐infrared. The current library includes the comprehensive characterization of 16 prospective dyes for fluorescence applications. Among them, several fluorene derivatives bearing different conjugation anchors were tested for coupling and demonstrated to preserve the photophysical responses once further bound.     

Fluorescent Pyranoindole Congeners: Synthesis and Photophysical Properties of Pyrano[3,2-f], [2,3-g], [2,3-f], and [2,3-e]Indoles

This paper reports the synthesis of four types of annulated pyranoindole congeners: pyrano[3,2-f]indole, pyrano[2,3-g]indole, pyrano[2,3-f]indole, and pyrano[2,3-e]indole and photophysical studies in this series. The synthesis of pyrano[3,2-f], [2,3-g], and [2,3-e]indoles involve a tandem of Bischler–Möhlau reaction of 3-aminophenol with benzoin to form 6-hydroxy- or 4-hydroxyindole followed by Pechmann condensation of these hydroxyindoles with β-ketoesters. Pyrano[2,3-f]indoles were synthesized through the Nenitzescu reaction of p-benzoquinone and ethyl aminocrotonates and subsequent Pechmann condensation of the obtained 5-hydroxyindole derivatives. Among the pyranoindoles studied, the most promising were pyrano[3,2-f] and [2,3-g]indoles. These compounds were characterized by moderate to high quantum yields (30–89%) and a large (9000–15,000 cm⁻¹) Stokes shift. More detailed photophysical studies were carried out for a series of the most promising derivatives of pyrano[3,2-f] and [2,3-g]indoles to demonstrate their positive solvatochromism, and the data collected was analyzed using Lippert-Mataga equation. Quantum chemical calculations were performed to deepen the knowledge of the absorption and emission properties of pyrano[3,2-f] and [2,3-g]indoles as well as to explain their unusual geometries and electronic structures.     

The Biosynthesis Related Enzyme,Structure Diversity and Bioactivity Abundance of Indole-Diterpenes: A Review

Indole diterpenes are a large class of secondary metabolites produced by fungi, possessing a cyclic diterpenoid backbone and an indole moiety. Novel structures and important biological activity have made indole diterpenes one of the focuses of synthetic chemists. Although the discovery, identification, structural diversity, biological activity and especially structure–activity relationship of indole diterpenes have been reported in some papers in recent years, they are absent of a systematic and comprehensive analysis, and there is no elucidation of enzymes related to this kind of natural product. Therefore, it is necessary to summarize the relevant reports to provide new perspectives for the following research. In this review, for the first time, the function of related synthases and the structure–activity relationship of indole diterpenes are expounded, and the recent research advances of them are emphasized.     

Exploration of versatile reactions on 2-chloro-3-nitroimidazo[1,2-a]pyridine: expanding structural diversity of C2- and C3-functionalized imidazo[1,2-a]pyridines

Alternative strategies for functionalizing 2-chloro-3-nitroimidazo[1,2-a]pyridine have been developed. Suzuki–Miyaura cross-coupling reaction provided easily the corresponding 2-arylated compounds, and herefrom the nitro group was reduced into amine which afforded amides, anilines, and ureas in the 3-position. The amination of the key compound using a metal-catalyzed reaction was reported. This study highlighted the importance of the nitro group to facilitate the chlorine displacement. Other nucleophilic aromatic substitutions open a route to various products derived from imidazo[1,2-a]pyridine.     

Cobalt(III)‐Catalyzed Intramolecular Cross‐Dehydrogenative C−H/X−H Coupling: Efficient Synthesis of Indoles and Benzofurans

An efficient cobalt(III)‐catalyzed intramolecular cross‐dehydrogenative C?H/N?H coupling of ortho‐alkenylanilines has been developed utilizing O₂ as a terminal oxidant. The developed reaction tolerates various reactive functional groups and allows the synthesis of diverse indole derivatives in good to excellent yields. The method was successfully extended to the synthesis of benzofurans through the intramolecular cross‐dehydrogenative C?H/O?H coupling of ortho‐alkenylphenols.     

Evaluation of the Saponin Content in Panax vietnamensis Acclimatized to Lam Dong Province by HPLC–UV/CAD

Panax vietnamensis, or Vietnamese ginseng (VG), an endemic Panax species in Vietnam, possesses a unique saponin profile and interesting biological activities. This plant is presently in danger of extinction due to over-exploitation, resulting in many preservation efforts towards the geographical acclimatization of VG. Yet, no information on the saponin content of the acclimatized VG, an important quality indicator, is available. Here, we analyzed the saponin content in the underground parts of two- to five-year-old VG plants acclimatized to Lam Dong province. Nine characteristic saponins, including notoginsenoside-R1, ginsenoside-Rg1, -Rb1, -Rd, majonoside-R1, -R2 vina-ginsenoside-R2, -R11, and pseudoginsenoside-RT4, were simultaneously determined by HPLC coupled with UV and with a charged aerosol detector (CAD). Analyzing the results illustrated that the detection of characteristic ocotillol-type saponins in VG by CAD presented a superior capacity compared with that of UV, thus implying a preferential choice of CAD for the analysis of VG. The quantitative results indicating the saponin content in the underground parts of VG showed an increasing tendency from two to five years old, with the root and the rhizome exhibiting different saponin accumulation patterns. This is the first study that reveals the preliminary success of VG acclimatization and thereby encourages the continuing efforts to develop this valuable saponin-rich plant.