Photoredox-Catalyzed Three-Component Amidoheteroarylation of Unactivated Alkenes.

A photoredox-catalyzed 1,2-amidoheteroarylation of unactivated alkenes with O-acyl hydroxylamine derivatives and heterocycles is presented. A range of heterocycles, including quinoxaline-2(1H)-ones, azauracils, chromones, and quinolones, are capable for this process, allowing the direct synthesis of valuable heteroarylethylamine derivatives. Structurally diverse reaction substrates, including drug-based scaffolds, were successfully applied, demonstrating the practicality of this method.

Photoinduced Radical Sulfinylation of C(sp3)-H Bonds with Sulfinyl Sulfones.

A direct C(sp3)-H sulfinylation reaction of alkanes with sulfinyl sulfones via decatungstate photocatalysis is reported. The sulfinyl sulfones generated in situ from sulfinates in the presence of an acylating reagent were able to trap the alkyl radicals that were produced via the photoinduced direct hydrogen atom transfer of alkanes, leading to a range of sulfoxides. This radical sulfinylation process provides an efficient and concise method for the synthesis of sulfoxides from abundant alkanes under mild conditions. Using the same strategy, aldehydes can also be transferred to the corresponding sulfoxides via decarbonylative sulfinylation.

Mechanism of the improved Fe(III)/persulfate reaction by gallic acid for ibuprofen degradation.

Gallic acid (GA), a natural plant polyphenol, was applied as amendment of Fe(III)/persulfate (PS) system for ibuprofen (IBP) degradation in this study. The impacts of all agentia (GA, Fe(III), PS) concentration and initial pH values on IBP removal efficiency were investigated, and their corresponding observed pseudo-first-order rate constants (kobs) were calculated. The addition of GA has significantly improved elimination efficiency of IBP due to the enhanced Fe(III)/Fe(II) cycle. Electron paramagnetic resonance (EPR) results confirmed that SO4•-, HO• and O2•- were involved in GA/Fe(III)/PS system. However, quenching experiments further affirmed the impact of SO4•- and HO• towards IBP decomposition instead of O2•-, with contribution ratio to IBP removal was 69.12% and 30.88%, respectively. SO4•- was the main radicals formed by directly activation of PS with Fe(II), while HO• was the transformation product of SO4•-. Based on instrumental analysis (stopped-flow UV-vis spectrum and MS) and theoretical calculation, the potential reaction mechanism between GA and Fe(III) in the presence of PS was further proposed. GA complexed with Fe(III) firstly and the Fe(III)-GA complex was then converted into quinone substance, accompanied by the generation of Fe(II). Furthermore, the application of GA extended the optimal pH range to neutral as well, which made it a promising treatment in practical application.

Transition-Metal-Free Intramolecular Radical Aminoboration of Unactivated Alkenes.

An efficient transition-metal-free cyclizing radical aminoboration of unactivated alkenes is reported. The B2(OH)4 reagent was used as the boron source, and the interaction between B2(OH)4 and an aryloxyamide N-radical precursor enabled the chain reaction to be initiated upon irradiation in the absence of any catalyst. This transformation proceeds via cyclization of an N-radical with subsequent intermolecular C-radical borylation. The cascade shows a broad scope and provides a wide range of high-value cyclic 1,2-aminoboronic esters.

Role of integrin­linked kinase in static compressive stress­induced autophagy via phosphatidylinositol 3 kinase in human periodontal ligament cells.

Orthodontic tooth movement (OTM) is achieved by using mechanical stimuli, which lead to the remodeling of periodontal tissues. Previous findings have demonstrated that autophagy may be one of the cell responses to mechanical stress. As a key structure in the integrin pathway, integrin linked­kinase (ILK) may play a role in the transmission of these mechanical signals. In addition, ILK is an important upstream molecule that regulates autophagy, under the influence of phosphatidylinositol 3 kinase (PI3K). Therefore, exploring the effect of mechanical stress on autophagy and the associated role of ILK/PI3K is of utmost significance to understanding the mechanism behind OTM. In the present study, human periodontal ligament cells (hPDLCs) were embedded into a collagen­alginate complex hydrogel for three­dimensional (3D) culturing. Static compressive stress (2.5 g/cm2) was loaded using the uniform weight method for 5, 15, 30, and 60 min. The autophagy of hPDLCs was detected by the expression of Beclin­1 (BECN1) and ATG­5 using RT­qPCR and LC3, respectively, using immunofluorescence. The results showed that the level of autophagy and gene expression of ILK increased significantly under static compressive stress. In ILK­silenced cells, static compressive stress could also upregulate ILK expression and increase the levels of autophagy. After PI3K inhibition, the increase in the autophagy level and the upregulation of ILK expression disappeared. These findings suggest that static compressive stress can induce autophagy in hPDLCs in a rapid, transient process, regulated by ILK and PI3K. Moreover, this static stress can upregulate ILK expression in a PI3K­dependent manner.

Photo-Mediated Intermolecular Coupling of Alkenes with Ketones via Acyloxy Nitroso Compounds.

An atom-economic intermolecular radical addition reaction of acyloxy nitroso compounds to electron-deficient alkenes mediated by visible light is reported. The starting nitroso derivatives are readily prepared by oxidation of the corresponding oximes prepared from ketones and the overall transformation represents an oxidative coupling of a ketone with a Michael acceptor. The cascade proceeds smoothly under mild conditions, providing a series of valuable functionalized oximes in moderate to good yields. Mechanistic studies suggest that these cascades proceed via addition/coupling processes that are controlled by the persistent radical effect (PRE) with NO acting as the persistent species.

Asymmetric Synthesis of Heterocyclic γ-Amino-Acid and Diamine Derivatives by Three-Component Radical Cascade Reactions.

An enantioselective three-component radical reaction of quinolines or pyridines with enamides and α-bromo carbonyl compounds by dual photoredox and chiral Brønsted acid catalysis is presented. A range of valuable chiral γ-amino-acid derivatives are accessible in high chemo-, regio-, and enantioselectivity from simple, readily available starting materials under mild reaction conditions. Using the same strategy, the asymmetric synthesis of 1,2-diamine derivatives is also reported.

Photoredox-catalyzed sulfonylation of alkyl iodides, sulfur dioxide, and electron-deficient alkenes.

A photoredox-catalyzed sulfonylation of alkyl iodides, sulfur dioxide, and electron-deficient alkenes under mild conditions is achieved. This reaction proceeds through alkyl radicals formed in situ from alkyl iodides under visible light irradiation in the presence of a photoredox catalyst. The alkyl radical intermediates would react with sulfur dioxide leading to alkylsulfonyl radicals, which would be trapped by electron-deficient alkenes giving rise to alkyl sulfones. Various functional groups including nitro, halo, acetyl, sufonyl, and pyridinyl are all tolerated under the photoredox conditions.

Photoinitiated Three-Component α-Perfluoroalkyl-ß-heteroarylation of Unactivated Alkenes via Electron Catalysis.

A visible-light-initiated α-perfluoroalkyl-ß-heteroarylation of various alkenes with perfluoroalkyl iodides and quinoxalin-2(1 H)-ones is presented. This three-component radical cascade reaction allows an efficient synthesis of a range of perfluoroalkyl containing quinoxalin-2(1 H)-one derivatives in moderate to excellent yields under mild conditions. Reactions proceed via acidic aminyl radicals that are readily deprotonated to give the corresponding radical anions able to sustain the radical chain as single electron transfer reducing reagents. Hence, the overall cascade classifies as an electron-catalyzed process.

Synthesis of Aromatic Sulfonamides through a Copper-Catalyzed Coupling of Aryldiazonium Tetrafluoroborates, DABCO·(SO2)2, and N-Chloroamines.

A copper-catalyzed aminosulfonylation of aryldiazonium tetrafluoroborates, DABCO·(SO2)2, and N-chloroamines is described. This coupling reaction provides an efficient and simple approach to a wide range of sulfonamides in moderate to good yields under mild conditions. Mechanistic investigation suggests that a radical process and transition-metal catalysis are merged in this tandem reaction.

Synthesis of ß-Keto Sulfones by a Catalyst-Free Reaction of Aryldiazonium Tetrafluoroborates, Sulfur Dioxide, and Silyl Enol Ethers.

A green approach for the generation of ß-keto sulfones through a reaction of aryldiazonium tetrafluoroborates and sulfur dioxide with silyl enol ether under catalyst- and additive-free conditions has been realized. This reaction proceeds efficiently at room temperature and goes to completion in half an hour. During the reaction process, aryldiazonium tetrafluoroborate is treated with DABCO⋅(SO2 )2 (DABCO=1,4-diazabicyclo[2.2.2]octane) to provide a sulfonyl radical as the key intermediate, which then initiates the transformation. Oxidants or metal catalysts are avoided, and the presence of DABCO also plays an important role in the reaction.

PTENp1, a natural sponge of miR-21, mediates PTEN expression to inhibit the proliferation of oral squamous cell carcinoma.

PTENp1, non-coding RNA (ncRNA) pseudogene, is involved in oral squamous cell carcinoma (OSCC). The precise effects mediated by PTENp1 transcripts within intricate regulatory networks involving molecular interactions with ancestral gene PTEN and tumorigenicity in OSCC remain unclear. Here, we found that PTENp1 was aberrantly expressed in OSCC. There was a positive correlation between the expression levels of PTENp1 and PTEN. Further, we showed that PTENp1 acted as a competing endogenous RNA that protects PTEN transcripts from being inhibited by miR-21, and consequently inhibited proliferation and colony formation and triggered S-G2/M cell cycle arrest through the AKT pathway. Also, the homogeneous relationship between expression of PTENp1 and PTEN was confirmed in OSCC tumor xenografts. Finally, low expression of PTENp1 and PTEN was negatively associated with histological differentiation and OSCC prognosis. The present work provided the first evidence for the extraordinary crosstalk among PTENp1, PTEN, and miR-21, and rendered a new light on the treatment of OSCC. © 2016 Wiley Periodicals, Inc.

Route for the Generation of Trifluoromethyl-Substituted Pyrrplo[3,2-c]quinolines.

Generation of trifluoromethyl-substituted pyrrolo[3,2-c]quinolines via a copper(II)-catalyzed tandem reaction of N-(σ-iodoaryl)alkynylimines with 2-isocyanoacetates is reported. The process involves a [3 + 2] cycloaddition and intramolecular C-C bond coupling, leading to the fluorine-containing N-heterocycles under mild conditions with high efficiency.

Generation of Sulfonyl Radicals from Aryldiazonium Tetrafluoroborates and Sulfur Dioxide: The Synthesis of 3-Sulfonated Coumarins.

A catalyst-free approach for the generation of sulfonyl radicals from aryldiazonium tetrafluoroborates in the presence of DABCO⋅(SO2 )2 is realized. The combination of aryldiazonium tetrafluoroborates, DABCO⋅(SO2 )2 , and aryl propiolates affords 3-sulfonated coumarins in good to excellent yields. This tandem reaction process involves radical addition, spirocyclization, and 1,2-migration of esters. Additionally, the in situ diazotization of a number of anilines allows the directional synthesis of desired 3-sulfonated coumarins in a one-pot, two-step process.

A four-component reaction of aryldiazonium tetrafluoroborates, sulfur dioxide, 1,2-dibromoethane, and hydrazines.

A four-component reaction of aryldiazonium tetrafluoroborates, sulfur dioxide, 1,2-dibromoethane, and hydrazines under metal-free conditions is described, providing a novel and efficient approach to 2-arylsulfonyl hydrazones. This transformation proceeds smoothly via insertion of sulfur dioxide under mild conditions with good functional group tolerance.

Synthesis of 1-(2,3-dihydrobenzofuran-3-yl)-methanesulfonohydrazides through insertion of sulfur dioxide.

A three-component reaction of 2-(allyloxy)anilines, sulfur dioxide and hydrazines under mild conditions is developed, which gives rise to 1-(2,3-dihydrobenzofuran-3-yl)-methanesulfonohydrazides in good yields. This radical process involves an intramolecular 5-exo-cyclization and insertion of sulfur dioxide.

An unexpected copper(II)-catalyzed three-component reaction of quinazoline 3-oxide, alkylidenecyclopropane, and water.

An unexpected copper(II)-catalyzed three-component reaction of quinazoline-3-oxide, alkylidenecyclopropane and water under mild conditions is reported. This transformation including [3+2] cycloaddition and intramolecular rearrangement leads to N-(2-(5-oxa-6-azaspiro[2.4]hept-6-en-7-yl)phenyl)formamides in good yields.

Aminosulfonylation of aromatic amines, sulfur dioxide and hydrazines.

A facile route to aryl N-aminosulfonamides under mild conditions is provided. The reaction of aromatic amines (including heteroaromatic amines), sulfur dioxide, and hydrazines proceeds efficiently with good functional group tolerance. The in situ generated diazonium ion is involved in the aminosulfonylation process.

Metal-free aminosulfonylation of aryldiazonium tetrafluoroborates with DABCO⋠(SO2)2 and hydrazines.

The coupling of aryldiazonium tetrafluoroborates, DABCO⋅(SO2)2, and hydrazines under metal-free conditions leads to the formation of aryl N-aminosulfonamides. The reaction proceeds smoothly at room temperature and shows broad functional-group tolerance. A radical process is proposed for this transformation.

Generation of 3-(1H-pyrrol-3-yl)-1H-inden-1-ones via a tandem reaction of 1-(2-alkynylphenyl)-2-enone, 2-isocyanoacetate, and water.

A silver triflate-catalyzed tandem reaction of 1-(2-alkynylphenyl)-2-enone, 2-isocyanoacetate, and water provides a novel and efficient route for the delivery of 3-(1H-pyrrol-3-yl)-1H-inden-1-ones. Four bonds are formed during the tandem process.