Synthesis of 1-Aminoisoquinolines and Their Application in a Host-Guest Doped Strategy To Construct Ultralong Room-Temperature Phosphorescence Materials for Bioimaging.

Organic ultralong room-temperature phosphorescence (RTP) materials have attracted great attention for their wide applications in optoelectronic devices and bioimaging. However, the development of these materials remains a challenging task, partially due to the lack of rational molecular design strategies and unclear luminescence mechanisms. Herein, we present a method for facile access to structurally diverse substituted 1-aminoisoquinoline derivatives through a copper-catalyzed one-pot three-component coupling reaction that provides a promising approach to rapidly assemble a library of 1-aminoisoquinolines for exploring the regularity of the host-guest doped system. A series of host-guest RTP materials with wide-ranging lifetimes from 4.4 to 299.3 ms were constructed by doping various substituted isoquinolines derivatives into benzophenone (BP). Furthermore, 4 r/BP nanoparticles could be used for in-vivo imaging with a signal-to-noise ratio value as high as 32, revealing the potential of the isoquinoline framework for the construction of high-performance RTP materials.

Palladium-Catalyzed Multicomponent Cascade Reaction of 3-Hydroxypropionitrile: Synthesis of Substituted Dihydrochalcones.

Direct access to substituted dihydrochalcones from the easily available starting materials 3-hydroxypropionitrile derivatives and arylboronic acids is described. The procedure involves a multicomponent aryl addition/hydroxyl elimination/reduction Heck approach in the presence of a Pd catalyst with excellent functional group tolerance and a wide range of substrates. In addition, mixed 1,3-diarylation of 3-hydroxypropanenitrile using two arylboronic acids with different electronic properties was also achieved.

Rational Design of a Near-Infrared Ratiometric Probe with a Large Stokes Shift: Visualization of Polarity Abnormalities in Non-Alcoholic Fatty Liver Model Mice.

Tracking liver polarity with noninvasive and dynamic imaging techniques is helpful to better understand the non-alcoholic fatty liver (NAFL). Herein, a novel near-infrared (NIR) fluorescent probe Cy-Mp is constructed using a "symmetry collapse" strategy. The structure modification leads to the conversion of locally excited state fluorescence to charge transfer state fluorescence. Cy-Mp emits at near-infrared (NIR) wavelengths with high photostability as well as a large Stokes shift. Cy-Mp exhibits a ratiometric response to polarity, providing more accurate analysis of intracellular polarity via the built-in internal reference correction. Most importantly, the in vivo studies indicate that Cy-Mp can accumulate in the liver and the decreased polarity in the liver of mice with NAFL is verified by the ratiometric imaging, implying the great potential of Cy-Mp in the diagnosis of NAFL.

Selective Synthesis of ß-Ketonitriles via Catalytic Carbopalladation of Dinitriles.

A practical, convenient, and highly selective method of synthesizing ß-ketonitriles from the Pd-catalyzed addition of organoboron reagents to dinitriles has been developed. This method provides excellent functional-group tolerance, a broad scope of substrates, and the convenience of using commercially available substrates. The method is expected to show further utility in future synthetic procedures.

Synthesis of 3-Selenylindoles through Organoselenium-Promoted Selenocyclization of 2-Vinylaniline.

A novel metal-free one-pot protocol for the synthesis of potential biologically active molecules 3-selenylindoles via intramolecular cyclization/selenylation with simple 2-vinylaniline has been developed with moderate to good yield, thus representing it as a facile route to diverse substitution patterns around the indole core. The reaction proceeded smoothly with a broad substrate scope and excellent functional group tolerance. Moreover, the present synthetic route could be readily scaled up to gram quantity without difficulty. Mechanistic studies have revealed that in situ formed selenium electrophile species may be the key intermediate for the selenocyclization process.

Pd-Catalyzed Approach for Assembling 9-Arylacridines via a Cascade Tandem Reaction of 2-(Arylamino)benzonitrile with Arylboronic Acids in Water.

A novel palladium-catalyzed protocol for the synthesis of 9-arylacridines via tandem reaction of 2-(arylamino)benzonitrile with arylboronic acids in water has been developed with good functional group tolerance. The present synthetic route could be readily scaled up to gram quantity without difficulty. This methodology was further extended to the synthesis of a 4'-OH derivative, which showed estrogenic biological activity. Preliminary mechanistic experiments showed that this transformation involves a nucleophilic addition of aryl palladium species to the nitrile to generate an aryl ketone intermediate followed by an intramolecular Friedel-Crafts acylation and dehydration to acridines.

Syntheses of Pyrroles, Pyridines, and Ketonitriles via Catalytic Carbopalladation of Dinitriles.

The first example of the Pd-catalyzed addition of organoboron reagents to dinitriles, as an efficient means of preparing 2,5-diarylpyrroles and 2,6-diarylpyridines, has been discussed here. Furthermore, the highly selective carbopalladation of dinitriles with organoboron reagents to give long-chain ketonitriles has been developed as well. Based on the broad scope of substrates, excellent functional group tolerance, and use of commercially available substrates, the Pd-catalyzed addition reaction of arylboronic acid and dinitriles is expected to be significant in future synthetic procedures.

Tandem addition/cyclization for synthesis of 2-aroyl benzofurans and 2-aroyl indoles by carbopalladation of nitriles.

The first example of the palladium-catalyzed tandem addition/cyclization of 2-(2-acylphenoxy)acetonitriles with arylboronic acids has been developed, providing a new strategy for the synthesis of 2-aroyl benzofurans with excellent chemoselectivity and wide functional group compatibility. Preliminary mechanistic experiments indicate that this tandem process involves sequential nucleophilic addition generating 2-(2-acylphenoxy)-1-phenylethan-1-one followed by an intramolecular cyclization. This methodology has also been applied to the synthesis of 2-aroyl indoles and the potent CYP19 inhibitor 1-(benzofuran-2-yl(phenyl)methyl)-1H-1,2,4-triazole.

Pd-Catalyzed Tandem Reaction of 2-Aminostyryl Nitriles with Arylboronic Acids: Synthesis of 2-Arylquinolines.

A novel palladium-catalyzed protocol for the synthesis of 2-arylquinolines via tandem reaction of 2-aminostyryl nitriles with arylboronic acids has been developed with good functional group tolerance. The presented approach offers a new synthetic pathway toward the core structures of 2-arylquinolines compared to classical condensation reaction of (E)-2-aminostyryl aryl ketones. Moreover, the present synthetic route could be readily scaled up to gram quantity without difficulty. Preliminary mechanistic experiments showed that this transformation involves a nucleophilic addition of aryl palladium species to the nitrile to generate an aryl ketone intermediate followed by an intramolecular cyclization and dehydration to quinoline ring.

Selenium-Catalyzed Oxidative C-H Amination of ( E)-3-(Arylamino)-2-styrylquinazolin-4(3 H)-ones: A Metal-Free Synthesis of 1,2-Diarylpyrazolo[5,1- b]quinazolin-9(1 H)-ones.

A novel metal-free catalysis protocol for the synthesis of 1,2-diarylpyrazolo[5,1- b]quinazolin-9(1 H)-ones via intramolecular oxidative C-H amination of ( E)-3-(arylamino)-2-styrylquinazolin-4(3 H)-ones has been developed in moderate to good yield. The method shows good functional group tolerance. The presented approach offers a new synthetic pathway toward the core structures of 2,3-fused quinazolinones. Moreover, the present synthetic route can be readily scaled up to gram quantity without difficulty. A possible mechanism involves a seleniranium ion followed by three-membered ring opening to form the C-N bond.

Efficient Tandem Addition/Cyclization for Access to 2,4-Diarylquinazolines via Catalytic Carbopalladation of Nitriles.

The first example of the palladium-catalyzed tandem addition/cyclization of 2-(benzylidenamino)benzonitriles with arylboronic acids has been developed. This transformation features good functional group tolerance and provides an alternative synthetic pathway to access 2,4-diarylquinazolines in moderate to good yields. A plausible mechanism for the formation of 2,4-diarylquinazolines involving sequential nucleophilic addition followed by an intramolecular cyclization is proposed.

Direct halosulfenylation of benzo[b]furans: a metal-free synthesis of 3-halo-2-thiobenzo[b]furans.

The first example of the direct halosulfenylation of benzo[b]furans with commercially available disulfides and N-halosuccinimides has been achieved, providing an efficient metal-free synthetic pathway to access diverse 3-halo-2-thiobenzo[b]furans in moderate to excellent yields. In particular, a halogen (e.g., bromo or iodo) substituent on the benzo[b]furan ring is amenable for further synthetic elaborations thereby broadening the diversity of the products.

Pd-Catalyzed tandem reaction of N-(2-cyanoaryl)benzamides with arylboronic acids: synthesis of quinazolines.

The synthesis of 2,4-disubstituted quinazolines by a palladium-catalyzed reaction of arylboronic acids with N-(2-cyanoaryl)benzamides has been developed with moderate to excellent yields. The method shows good functional group tolerance. In particular, halogen and hydroxyl substituents, which are amenable for further synthetic elaborations, are well tolerated. Moreover, the present synthetic route could be readily scaled up to gram quantity without difficulty. The mechanism possibly involves nucleophilic addition to the nitrile function, forming an imine intermediate followed by an intramolecular addition to the amide and dehydration to the quinazoline ring.

The Development of a Palladium-Catalyzed Tandem Addition/Cyclization for the Construction of Indole Skeletons.

A palladium-catalyzed tandem addition/cyclization of 2-(2-aminoaryl)acetonitriles with arylboronic acids has been developed for the first time, achieving a new strategy for direct construction of indole skeletons. This system shows good functional group tolerance and remarkable chemoselectivity. In particular, the halogen (e.g., bromo and iodo) substituents are amenable to further synthetic elaborations thereby broadening the diversity of the products. Preliminary mechanistic experiments indicate that this transformation involves sequential nucleophilic addition followed by an intramolecular cyclization.

Copper-Catalyzed Three-Component Coupling Reaction of Azoles, Se Powder, and Aryl Iodides.

A copper-catalyzed three-component coupling reaction of azoles, Se powder, and aryl iodide is described for the first time. This transformation provides a straightforward and facile pathway to synthesis 2-arylselanyl-azoles via a copper-catalyzed double C-Se bonds formation process. This reaction is attractive and practical since the cheap copper catalyst is employed and it does not require ligands, proceeds in generally good yields, and has a broad range of functional groups tolerance.

Palladium-catalyzed tandem addition/cyclization in aqueous medium: synthesis of 2-arylindoles.

An efficient protocol to construct 2-arylindoles was developed through palladium-catalyzed tandem addition/cyclization of potassium aryltrifluoroborates with aliphatic nitriles in aqueous medium. The use of water as the reaction medium makes the synthesis process environmentally benign. A plausible mechanism for the formation of 2-arylindoles involving sequential nucleophilic addition followed by an intramolecular cyclization is proposed. Moreover, the utility of this catalytic tandem transformation was also demonstrated in an efficient gram-scale synthesis. This method provides an alternative synthetic tool for accessing a more diverse array of 2-arylindoles.

Copper-catalyzed C-O bond cleavage and cyclization: synthesis of indazolo[3,2-b]quinazolinones.

The first example of a copper-catalyzed halogen-free protocol to construct indazolo[3,2-b]quinazolinones was developed through sequential inert C-O bond cleavage followed by intramolecular C-N bond formation. This protocol represents an efficient synthetic tool for accessing a more diverse range of functionalized indazolo[3,2-b]quinazolinones. The structure of the newly synthesized indazolo[3,2-b]quinazolinones was unambiguously confirmed by X-ray crystal diffraction analysis.

Efficient Approach to Carbinol Derivatives through Palladium-Catalyzed Base-Free Addition of Aryltriolborates to Aldehydes.

Palladium-catalyzed base-free addition of aryltriolborates to aldehydes has been developed, leading to a wide range of carbinol derivatives in good to excellent yields. The efficiency of this transformation was demonstrated by compatibility with a wide range of functional groups. The present synthetic route to carbinol derivatives could be readily scaled up to gram quantity without difficulty. Thus, this method represents a simple and practical procedure to access carbinol derivatives.

Copper-Catalyzed Three-Component Reaction for Regioselective Aryl- and Heteroarylselenation of Indoles using Selenium Powder.

A new and efficient copper-catalyzed C3 aryl- and heteroarylselenation of indoles employing selenium powder has been developed. The advantages of this chemistry involve the use of cheap selenating reagents, tolerance of a variety of functional groups, and practicality. In addition, this protocol has been further elaborated in an intramolecular phenylselenation of a (hetero) aryl C-H bond to construct an important motif of benzoselenopheno[3,2-b]indole. A preliminary mechanism study suggests that the reaction starts with a Ullman-type selenation between aryl iodides and selenium, followed by an oxidative cross-coupling with indole. The utility of this method has been demonstrated in an efficient gram-scale synthesis and an application to the synthesis of tubulin polymerization inhibitor.

Copper-Catalyzed Oxirane-Opening Reaction with Aryl Iodides and Se Powder.

Using Se powder as the selenating reagent, the copper-catalyzed double C-Se cross-coupling of aryl iodides, epoxides, and elemental selenium has been developed. This strategy provides a straightforward approach to the synthesis of ß-hydroxy phenylselenides with excellent regioselectivity of the ring opening reaction. This process proceeds in generally good yields and is compatible with a broad range of functional groups.