Radical Phosphorylation of Aliphatic C-H Bonds via Iron Photocatalysis.

The synthesis of tertiary phosphines(III) has been a long-standing challenge in synthetic chemistry because of inevitable issues including harsh conditions, sensitive organometallic reagents, and prefunctionalized substrates in traditional synthesis. Herein, we report a strategically novel C(sp3)-H bond phosphorylation that enables the assembly of structurally diverse tertiary phosphines(III) from industrial phosphine(III) sources under mild photocatalytic conditions. The merger of ligand-to-metal charge transfer (LMCT) of FeCl3 with the hydrogen atom-transfer (HAT) process is the key for the generation of alkyl radicals from hydrocarbons. Strikingly, this catalytic system can be successfully applied for the polymerization of electron-deficient alkenes.

Organo-cyanamides: convenient reagents for catalytic amidation of carboxylic acids.

An unprecedented DMAP-catalysed amidation of aryl and alkyl carboxylic acids with organo-cyanamides has been developed. Unlike the use of N-cyano-N-phenyl-p-methylbenzenesulfonamide (NCTS) as an electrophilic cyanating reagent, an unusual desulfonylation/decyanation reaction model has been disclosed for the first time. Remarkable features of this reaction include readily available substrates, simple operation and broad scope, enabling the efficient synthesis of structurally diverse amides. The synthetic utility of this protocol was demonstrated by the late-stage amidation of bioactive carboxylic acids and a scale-up reaction.

Merging Annulation with Ring Deconstruction: Synthesis of (E)-3-(2-Acyl-1H-benzo[d]imidazol-4-yl)acrylaldehyde Derivatives via I2/FeCl3-Promoted Dual C(sp3)-H Amination/C-N Bond Cleavage.

An unprecedented I2/FeCl3-promoted cascade reaction of aryl methyl ketones with 8-aminoquinolines for the convenient synthesis of (E)-3-(2-acyl-1H-benzo[d]imidazol-4-yl)acrylaldehydes was developed by merging annulation with ring deconstruction. This novel strategy unlocked the new reactivity of 8-aminoquinolines and provided an attractive platform for the ring opening of unactivated N-heteroaromatic compounds. Preliminary mechanistic investigation suggested that dual C(sp3)-H amination/C-N bond cleavage were key reaction steps. Furthermore, late-stage modification of the obtained products successfully delivered pyrazole and isoxazole derivatives, increasing the practicability and application potential of this methodology in organic synthesis.

Copper-Catalyzed Multicomponent Domino Reaction of 2-Bromobenzaldehydes, Aryl Methyl Ketones, and Sodium Azide: Access to 1 H-[1,2,3]Triazolo[4,5- c]quinoline Derivatives.

A practical copper-catalyzed multicomponent reaction has been developed for the synthesis of 1 H-[1,2,3]triazolo[4,5- c]quinoline derivatives from commercially available 2-bromobenzaldehydes, aryl methyl ketones, and sodium azide. This protocol integrated consecutive base-promoted condensation, [3 + 2] cycloaddition, copper-catalyzed SNAr, and denitrogenation cyclization sequences. Preliminary mechanistic studies revealed that CuBr2 acted as a multifunctional catalyst to streamline this domino process. The mild catalytic system enabled effective construction of one C-C and four C-N bonds in one operation.

Switchable Access to 3-Carboxylate-4-quinolones and 1-Vinyl-3-carboxylate-4-quinolones via Oxidative Cyclization of Isatins and Alkynes.

An efficient transition-metal-free oxidative cyclization reaction using isatins and alkynes for the facile synthesis of structurally diverse 4-quinolones has been developed. Intriguingly, switchable access to substituted 3-carboxylate-4-quinolones and 1-vinyl-3-carboxylate-4-quinolones could be achieved by choosing a different base in the reaction. The obtained products could undergo further transformations, increasing the application potential of the method in organic synthesis.

Copper-catalyzed ambient-temperature decarboxylative annulation of isatins with amidine hydrochlorides: a facile access to 2-(1,3,5-triazin-2-yl)aniline derivatives.

A copper-catalyzed cascade reaction using isatins and amidine hydrochlorides for the synthesis of 2-(1,3,5-triazin-2-yl)aniline derivatives has been developed. This reaction features commercially available starting materials, mild reaction conditions and good functional group tolerance.

A concise construction of 12H-benzo[4,5]thiazolo[2,3-b]quinazolin-12-ones via an unusual TBHP/Na2CO3 promoted cascade oxidative cyclization and interrupted Dimroth rearrangement.

An efficient transition-metal-free cascade reaction has been developed for the facile synthesis of 12H-benzo[4,5]thiazolo[2,3-b]quinazolin-12-one derivatives from commercially available isatins and 2-haloaryl isothiocyanates. A preliminary mechanistic study suggested an interrupted Dimroth rearrangement was the key step for the successful transformation.

Substrates as Electron-Donor Precursors: Synthesis of Naphtho-Fused Oxindoles via Benzannulation of 2-Halobenzaldehydes and Indolin-2-ones.

An unusual benzannulation reaction has been realized by integrating intermolecular adol condensation with subsequent intramolercular base-promoted homolytic aromatic substitution. This novel cascade reaction provides a straightforward approach toward various naphtho-fused oxindoles from 2-halobenzaldehydes and indolin-2-ones in the presence of Cs2CO3 in DMSO. The enolates of indolin-2-ones as new and internal electron donors have been demonstrated to initiate intramolecular radical dehalogenative coupling.

Divergent Synthesis of Quinazolin-4(3H)-ones and Tryptanthrins Enabled by a tert-Butyl Hydroperoxide/K3PO4-Promoted Oxidative Cyclization of Isatins at Room Temperature.

A synergetic tert-butyl hydroperoxide/K3PO4-promoted oxidative cyclization has been developed for the facile synthesis of various functionalized quinazolin-4(3H)-ones from commercially available isatins and amidine hydrochlorides at room temperature. The synthetic utility of this strategy was illustrated by the convenient synthesis of tryptanthrin derivatives via a self-dimerization of isatins under the same conditions.

Copper-Catalyzed Multicomponent Domino Reaction of 2-Bromoaldehydes, Benzylamines, and Sodium Azide for the Assembly of Quinazoline Derivatives.

An efficient three-component domino reaction of 2-bromoaldehydes, benzylamines, and sodium azide has been developed for the synthesis of quinazoline derivatives. This domino process involves copper-catalyzed SNAr, oxidation/cyclization, and denitrogenation sequences. The mild catalytic system enabled the effective construction of three C-N bonds in one operation.

Expeditious Synthesis of 2-Phenylquinazolin-4-amines via a Fe/Cu Relay-Catalyzed Domino Strategy.

A highly efficient Fe/Cu relay-catalyzed domino protocol has been developed for the synthesis of 2-phenylquinazolin-4-amines from commercially available ortho-halogenated benzonitriles, aldehydes, and sodium azide. This elegant domino process involved consecutive iron-mediated [3 + 2] cycloaddition, copper-catalyzed SNAr, reduction, cyclization, oxidation, and copper-catalyzed denitrogenation sequences. The formed structure is the privileged core in drugs and bioactive molecules.

Consecutive Cycloaddition/S(N)Ar/Reduction/Cyclization/Oxidation Sequences: A Copper-Catalyzed Multicomponent Synthesis of Fused N-Heterocycles.

A highly efficient multicomponent domino protocol has been developed for the synthesis of 5-phenyl-[1,2,3]triazolo[1,5-c]quinazolines from simple and readily available (E)-1-bromo-2-(2-nitrovinyl)benzenes, aldehydes, and sodium azide. This elegant domino process involved consecutive [3 + 2] cycloaddition, copper-catalyzed S(N)Ar, reduction, cyclization, and oxidation sequences. Notably, sodium azide acted as a dual nitrogen source in the construction of this novel fused N-heterocycle.

Intramolecular decarboxylative coupling as the key step in copper-catalyzed domino reaction: facile access to 2-(1,3,4-oxadiazol-2-yl)aniline derivatives.

A copper-catalyzed domino protocol for the synthesis of 2-(1,3,4-oxadiazol-2-yl)aniline derivatives has been developed from simple and available isatins and hydrazides. This domino process integrated consecutive condensation, base-promoted ring-opening and the key copper-catalyzed decarboxylative coupling for intramolecular C-O bond formation.

An integration of condensation/Ullmann-type coupling/bicyclization sequences: copper-catalyzed three-component direct synthesis of [1,2,4]triazolo[1,5-b]isoquinolin-5(1H)-ones.

A highly efficient three-component domino protocol has been developed for the synthesis of [1,2,4]triazolo[1,5-b]isoquinolin-5(1H)-ones from simple and readily available o-halogenated benzohydrazides, aldehydes and nitriles. This domino process involves sequential selective condensation, copper-catalyzed intermolecular C-arylation and bicyclization. Notably, the use of ligands and anaerobic conditions can be avoided in this reaction.

A cascade coupling strategy for one-pot total synthesis of ß-carboline and isoquinoline-containing natural products and derivatives.

Multi-birds with one stone: A cascade coupling strategy was developed for the synthesis of ß-carbolines. The method can direct the synthesis of ß-carboline and isoquinoline-containing natural products with high yields. Moreover, this protocol can also be further applied towards the total synthesis of natural products fascaplysin and papaverin (see scheme).

Direct one-pot synthesis of luotonin F and analogues via rational logical design.

An efficient one-pot synthetic protocol has been proposed for the synthesis of luntonin F from easily available starting materials. Through a rational logical design, multifundamental reactions (iodination, Kornblum oxidation, and annulation) were assembled in one-pot. The developed approach can efficiently synthesize luntonin F and a diversity of analogues.

JNK phosphorylation promotes degeneration of cervical endplate chondrocytes through down-regulation of the expression of ANK in humans / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>C-Jun N-terminal kinase (JNK) signaling pathway and ankylosis gene (ANK) play a critical role in endplate chondrocytes degeneration. The purpose of this study was to investigate whether the expression levels of ANK was associated with the activation of JNK.</p><p><b>METHODS</b>Cartilage endplates of 49 patients were divided into the control group (n = 19) and the experimental group (n = 30). The patients in the control group were graded 0 and those in the experimental group were graded I-III according to Miller's classification. Endplate chondrocytes were isolated by enzyme digestion and cultured in vitro. The inverted phase contrast microscope, teluidine blue staining, HE staining, real time RT-PCR, and MTT were used to observe morphological appearances, biological characteristics, and growth curve of endplate chondrocytes from the cartilage endplate of the two groups. Real time RT-PCR and Western blotting were used to analyze the mRNA and protein expression levels of associated factors in the degeneration process in the cultured endplate chondrocytes with or without subjected SP600125.</p><p><b>RESULTS</b>The expression levels of type II collagen, aggrecan, and ANK in endplate chondrocytes of experimental group were lower than that of control group and phosphorylation level of JNK in the experimental group which was higher than that in the control group. Application of JNK phosphorylation inhibitor to degeneration chondrocytes resulted in a marked decrease in the phosphorylation level of JNK and a significant increase in the expression levels of type II collagen, aggrecan, and ANK.</p><p><b>CONCLUSION</b>The degeneration of the human cervical endplate chondrocytes might be promoted by JNK phosphorylation by down-regulating the expression of ANK.</p>

I2-CF3SO3H synergistic promoted sp3 C-H bond diarylation of aromatic ketones.

An I(2)-CF(3)SO(3)H synergistic promoted sp(3) C-H bond diarylation protocol was developed for the synthesis of 2,2-bis(4-(dimethylamino)phenyl)-1-aryl ethanones. The reaction performed well in the absence of any metal and ligand. It integrated three reactions with different mechanisms (iodination, Kornblum oxidation, and hydroarylation) in a single reactor.

I2 promoted domino oxidative cyclization for one-pot synthesis of 2-acylbenzothiazoles via metal-free sp3 C-H functionalization.

An I(2) promoted domino protocol was developed to construct 2-acylbenzothiazoles from simple and readily available aromatic ketones/unsaturated methyl ketones and o-aminobenzenethiols. The reaction proceeded smoothly under metal-free and peroxide-free conditions.

A multipathway coupled domino strategy: metal-free oxidative cyclization for one-pot synthesis of 2-acylbenzothiazoles from multiform substrates.

A multipathway coupled domino strategy has been developed for the efficient synthesis of 2-acylbenzothiazoles from multiform substrates arylethenes, arylacetylenes, 2-hydroxy-aromatic ketones, and carbinols via four distinct pathways. Through a logical coupled oxidation/heterocyclization domino process, a variety of 2-acylbenzothiazoles were synthesized free of metal in one pot.