Atmosphere- and Solvent-Controlled Coupling and Acetylation of Phenols Induced by Visible Light.

A tunable coupling or acetylation of phenol derivatives with diacetyl was enabled through the switch of the atmosphere and solvent induced by visible light under metal-free conditions. Symmetric and asymmetric diphenols or binaphthols were obtained under oxygen in water or 1,1,1,3,3,3-hexafluoroisopropanol, whereas phenol acetates were formed under argon in the presence of diacetyl and acetic acid. The possibility to control the chemo- and regioselectivities enriches the synthetic versatility of photoreactions.

Recent progress in photoinduced direct desulfurization of thiols.

The reduction of mercaptans plays an important role in diverse areas such as protein synthesis, polymer science, environmental study, and pharmaceutical chemistry. Despite significant advancements in this area, particularly in light-induced transformations, review articles have rarely been reported on this topic. Thus, this review article emphasizes the direct photoinduced desulfurization and functionalization of thiols to alkanes or coupling products, with a focus on significant advancements made in the last decade. The progress is discussed according to the types of bonds formed from the cleavage of Csp3-SH bonds.

Catalyst-free photo-reductions of aromatic olefins and carbonyl compounds.

We describe herein a catalyst-free, traditional reductant-free strategy for the direct photoinduced hydrogenation or deuteration of aromatic olefins, ketones, and aldehydes with simple bases as the only additives. A broad range of substrates were demonstrated with high yields and deuterium incorporations. Mechanistic experiments indicate a radical mechanism.

Catalyst-free generation of acyl radicals induced by visible light in water to construct C-N bonds.

We describe herein a catalyst-free and redox-neutral photochemical strategy for the direct generation of acyl radicals from α-diketones, and its selective conversion of nitrosoarenes to hydroxyamides or amides with AcOH or NaCl as an additive. The reaction was carried out under mild conditions in water with purple LEDs as the light source. A broad scope of substrates was demonstrated. Mechanistic experiments indicate that α-diketones cleave to give acyl radicals, with hydroxyamides being further reduced to amides.

Visible-Light-Induced Direct Difluoroalkylation of Uracils, Pyridinones, and Coumarins.

An efficient and general method for the synthesis of difluoroalkylated uracils, pyridinones, and coumarins through visible-light-induced reaction with commercial materials is developed. The strategy proceeds with high efficiency under mild reaction conditions and shows excellent functional group compatibility, even toward bromide and hydroxyl group, thus demonstrates high potent application in a late-stage fluoroalkylation. Moreover, the difluoroalkylated products can be further transformed to a diverse variety of difluoroalkylated heterocycles, including molecules of potential biological activity.

A New Ligustrazine Derivative-Selective Cytotoxicity by Suppression of NF-κB/p65 and COX-2 Expression on Human Hepatoma Cells. Part 3.

A new anticancer ligustrazine derivative, 3ß-hydroxyolea-12-en-28-oic acid- 3,5,6-trimethylpyrazin-2-methylester (T-OA, C38H58O3N2), was previously reported. It was synthesized via conjugating hepatoprotective and anticancer ingredients of traditional Chinese medicine. We found that T-OA exerted its anticancer activity by preventing the expression of nuclear transcription factor NF-κB/p65 and COX-2 in S180 mice. However, the selective cytotoxicity of T-OA on various kinds of cell lines has not been studied sufficiently. In the present study, compared with Cisplatin, T-OA was more toxic to human hepatoma cell line Bel-7402 (IC50 = 6.36 ± 1.56 µM) than other three cancer cell lines (HeLa, HT-29, BGC-823), and no toxicity was observed toward Madin-Darby canine kidney cell line MDCK (IC50 > 150 µM). The morphological changes of Bel-7402 cells demonstrated that T-OA had an apoptosis-inducing effect which had been substantiated using 4',6-diamidino-2-phenylindole (DAPI) staining, acridine orange (AO)/ethidium bromide (EB) staining, flow cytometry and mitochondrial membrane potential assay. Combining the immumohistochemical staining, we found T-OA could prevent the expression of NF-κB/p65 and COX-2 in Bel-7402 cells. Both of the proteins have been known to play roles in apoptosis and are mainly located in the nuclei. Moreover subcellular localization was performed to reveal that T-OA exerts in nuclei of Bel-7402 cells. The result was in accordance with the effects of down-regulating the expression of NF-κB/p65 and COX-2.

A Non-Bonding Interaction-Based Fluorescent Probe for Detection of Halogenated Carbonyl Compounds.

The fluorescent detection of neutral and volatile carbonyl halogenated compounds had not been studied before. We describe here a simple and sensitive turn-on rhodamin fluorescent probe for the selective detection of fluorinated/brominated/chlorinated/iodinated carbonyl compounds. A wide range of linear or cyclic volatile organic halides was detected with a limit of detection as low as 45.6 nM within 1 min. Mechanistic experiments and DFT calculations indicate the reversible formation of a 1:1 complex of sensor and analyst through non-bonding interaction.

A synthetic study of chiral α-hydroxy-H-phosphinates based on proline catalysis.

A highly enantioselective synthesis of α-hydroxyphosphinates was achieved based on the L-proline-catalyzed aldol reaction of α-acylphosphinates and acetone. Due to the preexisting chirality at the phosphorus center, mixtures of two diastereomers of the α-hydroxyphosphinates were obtained in moderate to good yields, with simultaneously high enantioselectivity for both diastereomers. The products could be converted into α-hydroxy-H-phosphinates with satisfactory yields. Furthermore, an unprecedented oxidation-reduction reaction of the α-hydroxyphosphinates or α-hydroxy-H-phosphinates to form phosphonates was observed, and the mechanism involved in such a chemical transformation is discussed.

Enantioselective synthesis of H-phosphinic acids bearing natural amino acid residues.

The first systematic study on the asymmetric synthesis of H-phosphinic acids bearing natural protein amino acid residues was reported on the basis of the asymmetric addition of ethyl diethoxymethylphosphinate to N-tert-butanesulfinyl imines. Good yields and moderate to high enantioselectivities were obtained. Reliable methods were developed for the elucidation of the stereochemistry of these phosphinic acids and derivatives thereof. The transformation of the side chains of these analogues was studied. Methods for the conversion of the α-aminophosphinates to oligopetides were reported.

Stereospecific transformation of protected P-H group into P-O or P-N group in one-pot reaction.

A general and efficient procedure for converting 1,1-diethoxyalkylphosphinates into phosphonates or phosphonamides is described by the application of bromine with moderate to high yields and good purity in a one-pot reaction. H-Phosphinate reacts stereospecifically with bromine and subsequently couples with nucleophile to form the corresponding optically active R(1)P(O)(OEt)X with retention of configuration at the phosphorus center. For α-amino-H-phosphinates, the transformation could be realized without the protection of the amino group.

Synthesis of Secondary Trifluoromethylated Alkyl Bromides Using 2-Bromo-3,3,3-trifluoropropene as a Radical Acceptor.

Herein, the first example using commercially available 2-bromo-3,3,3-trifluoropropene (BTP) as a radical acceptor has been reported. Taking advantage of this strategy, a wide range of secondary trifluoromethylated alkyl bromides were synthesized in good to excellent yields with broad functional group tolerance by using redox-active esters as a radical precursor. The practicality of this protocol was further demonstrated by diverse derivations and direct modification of biologically active molecules.

Catalyst-free and visible light promoted trifluoromethylation and perfluoroalkylation of uracils and cytosines.

Fluoroalkylated enaminones, such as trifluridine and 5-trifluoromethyluracil, have widespread applications in pharmaceuticals and agrochemicals. Although these kinds of pharmaceutical agent often bear CF3 and perfluoroalkyl motifs in the core structure, access to such analogues typically requires multi-step synthesis. Here, we report a mild, metal-free and operationally simple strategy for the direct perfluoroalkylation of uracils, cytosines and pyridinones through a visible-light induced pathway from perfluoroalkyl iodides. This photochemical transformation features synthetic simplicity, mild reaction conditions without any photoredox catalyst, and high functional group tolerance, providing a facile route for applications in medicinal chemistry.

Development of an indicator for the direct visualization of radical intermediates in organic reactions.

A color-indicator based on a derivative of rhodamine amide was developed for the detection of radical intermediates in organic reactions. This derivative showed sensitive color changes for various radical intermediates initiated by chemical reagents or UV light.