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.

Palladium-Catalyzed Cascade Reaction of o-Cyanobiaryls with Arylboronic Acids: Synthesis of 5-Arylidene-7-aryl-5H-dibenzo[c,e]azepines.

A palladium-catalyzed cascade reaction of 2'-acetyl-[1,1'-biphenyl]-2-carbonitriles with arylboronic acids is developed. This reaction affords a new class of seven-membered 5-arylidene-7-aryl-5H-dibenzo[c,e]azepines with good functional group compatibility and selectivity. Reaction mechanistic study suggests that this transformation involves carbopalladation of nitrile and subsequent intramolecular cyclization followed by oxidative Heck coupling.

Monodehydroascorbate Reductase Plays a Role in the Tolerance of Chlamydomonas reinhardtii to Photooxidative Stress.

Monodehydroascorbate reductase (MDAR; EC 1.6.5.4) is one of the key enzymes in the conversion of oxidized ascorbate (AsA) back to reduced AsA in plants. This study investigated the role of MDAR in the tolerance of Chlamydomonas reinhardtii P.A. Dangeard to photooxidative stress by overexpression and downregulation of the CrMDAR1 gene. For overexpression of CrMDAR1 driven by a HSP70A:RBCS2 fusion promoter, the cells survived under very high-intensity light stress (VHL, 1,800 µmol�m-2�s-1), while the survival of CC-400 and vector only control (vector without insert) cells decreased for 1.5 h under VHL stress. VHL increased lipid peroxidation of CC-400 but did not alter lipid peroxidation in CrMDAR1 overexpression lines. Additionally, overexpression of CrMDAR1 showed an increase in viability, CrMDAR1 transcript abundance, enzyme activity and the AsA: dehydroascorbate (DHA) ratio. Next, MDAR was downregulated to examine the essential role of MDAR under high light condition (HL, 1,400 µmol�m-2�s-1). The CrMDAR1 knockdown amiRNA line exhibited a low MDAR transcript abundance and enzyme activity and the survival decreased under HL conditions. Additionally, HL illumination decreased CrMDAR1 transcript abundance, enzyme activity and AsA:DHA ratio of CrMDAR1-downregulation amiRNA lines. Methyl viologen (an O2�- generator), H2O2 and NaCl treatment could induce an increase in CrMDAR1 transcript level. It represents reactive oxygen species are one of the factor inducing CrMDAR1 gene expression. In conclusion, MDAR plays a role in the tolerance of Chlamydomonas cells to photooxidative stress.

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.

Lanthanide-Catalyzed Tandem Insertion of Secondary Amines with 2-Alkynylbenzonitriles: Synthesis of Aminoisoindoles.

A lanthanide-catalyzed intermolecular hydroamination of 2-alkynylbenzonitriles with secondary amines has been disclosed, providing a streamlined access to a range of aminoisoindoles in moderate to excellent yields. The salient features of this reaction include high bond-formation efficiency, mild reaction conditions, 100 % atomic efficiency and good functional group tolerance. This methodology has also been successfully applied to the construction of other nitrogen-containing compounds, such as 5 H-imidazo[2,1-a]isoindoles and isoquinolines. A plausible mechanism for the formation of aminoisoindoles involving initial N-H activation by a lanthanide complex followed by C≡N insertion into a Ln-N bond to form an amidinate lanthanide intermediate, which undergoes the cyclization is proposed.

Palladium-Catalyzed Three-Component Tandem Process: One-Pot Assembly of Quinazolines.

The first example of the palladium-catalyzed, three-component tandem reaction of 2-aminobenzonitriles, aldehydes, and arylboronic acids has been developed, providing a new approach for one-pot assembly of diverse quinazolines in moderate to good yields. A noteworthy feature of this method is the tolerance of bromo and iodo groups, which affords versatility for further synthetic manipulations. Preliminary mechanistic experiments indicate that this tandem process involves two possible mechanistic pathways for the formation of quinazolines via catalytic carbopalladation of the cyano group.

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.

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.

Tandem Addition/Cyclization for Access to Isoquinolines and Isoquinolones via Catalytic Carbopalladation of Nitriles.

The first example of the palladium-catalyzed sequential nucleophilic addition followed by an intramolecular cyclization of functionalized nitriles with arylboronic acids has been achieved, providing an efficient synthetic pathway to access structurally diverse isoquinolines and isoquinolones. This methodology has also been successfully applied to the total synthesis of the topoisomerase I inhibitor CWJ-a-5 (free base).