C-N cleavage of secondary amide to access primary amide by a Co(II)/Oxone oxidation system.

Cleavage of the C-N bond of a secondary amide could provide alternative access to primary amides; however, this strategy remains challenging due to oxidation resistance of the amide. Herein, we employed the cobalt(II)/Oxone catalytic system, one of the advanced oxidation processes (AOPs), to make it available to break the strong C-N bond of various secondary (sulfon)amides, especially those bearing electron-poor or ortho-substituted N-arenes, en route to desirable primary (sulfon)amides. Control experiments showed that it was probably not the generally-considered persulfate anion radical in the cobalt/peroxymonosulfate (Co/PMS) system but the proposed high-valent cobalt-oxo intermediate that should be the major active species for the initial N-H oxidation of N-aryl amides. In the case of N-alkylated secondary amides, the α-C-H bond, rather than the N-H bond, should be oxidized first by both the reactive radicals and high-valent cobalt-oxo species. This work not only establishes an efficient method for removing the N-substituents of secondary amides at low cost, with readily available and eco-friendly reagents, but also demonstrates further synthetic application and provides more insight into intermediates for metal-based AOPs in environmental remediation.

Additive-free oxychlorination of unsaturated C-C bonds with tert-butyl hypochlorite and water.

Herein we report an additive-free protocol for the facile synthesis of α,α-dichloroketones and α-chlorohydrins from various aryl terminal, diaryl internal, and aliphatic terminal alkynes and alkenes, respectively. The commercially available tert-butyl hypochlorite (tBuOCl) was employed as a suitable chlorinating reagent, being accompanied by the less harmful tBuOH as the by-product. In addition, the oxygen atoms in the products came from water rather than molecular oxygen, based on the 18O-labelling experiments. Meanwhile, the diastereoselectivity of the Z- and the corresponding E-alkenes has been compared and rationalized. Using a group of control experiments, the possible mechanisms have been proposed as the initial electrophilic chlorination of unsaturated C-C bonds in a Markovnikov-addition manner in general followed by a nucleophilic addition with water. This work simplified the oxychlorination method with a mild chlorine source and a green oxygen source under ambient conditions.

Radical-Smiles Rearrangement by a Vitamin B2-Derived Photocatalyst in Water.

Herein, we report a catalytic radical-Smiles rearrangement system of arene migration from ether to carboxylic acid with riboflavin tetraacetate (RFT), a readily available ester of natural vitamin B2, as the photocatalyst and water as a green solvent, being free of external oxidant, base, metal, inert gas protection, and lengthy reaction time. Not only the known substituted 2-phenyloxybenzoic acids substrates but also a group of naphthalene- and heterocycle-based analogues was converted to the corresponding aryl salicylates for the first time. Mechanistic studies, especially a couple of kinetic isotope effect (KIE) experiments, suggested a sequential electron transfer-proton transfer processes enabled by the bifunctional flavin photocatalyst.

Alkyne Oxidation by a Vitamin B2-Based Photocatalytic System with Both H2O and O2 as the Oxygen Source.

The employment of readily available photocatalysts and green oxygen atom sources is recognized as a promising strategy to develop sustainable catalysis for oxidation reactions. We herein reported a sacrificial reagent-free system consisting of riboflavin tetraacetate (RFT), an ester of natural vitamin B2 as the photocatalyst, and Sc(OTf)3 and NaCl as the cocatalysts for alkyne oxidation under blue light or even sunlight irradiation to produce 1,2-diketone in which the oxygen atoms were from both water and molecular oxygen, respectively. A major Cl-/Cl• cycle was proposed to be involved and achieved by the excited [RFT-2Sc3+]* complex via single electron transfer for the first time, distinguished from the OCl- active species by a two-electron process in previous flavin-halide photo-oxidation systems.

Visible-light-induced aerobic epoxidation with vitamin B2-based photocatalyst.

Herein we described the catalytic epoxidation of α,ß-enone, with peroxide in situ generated, via a predominant single electron transfer and a minor energy transfer pathway. We use inexpensive natural vitamin B2 (riboflavin, RF) or its simple ester (riboflavin tetraacetate, RFT) as the photocatalysts, commonly used 1,8-diazabicyclo[5.4.0]-7-undecene (DBU) as both the electron source and organic base, and ambient air as the terminal oxidant, under visible-light irradiation and room temperature.

Fluorescent COFs with a Highly Conjugated Structure for Combined Starvation and Gas Therapy.

Covalent organic frameworks (COFs) show great potential in biomedicine, but the synthesis of fluorescent ones with a highly conjugated structure in mild conditions remains a challenge. Herein, we reported a facile method to synthesize a nanosized, highly conjugated, and N-enriched COF material with bright fluorescence and further integrated it as a novel nanoplatform for efficient cancer starvation/gas therapy. High surface area and a porous structure endowed COFs with large loading capacity for both glucose oxidase and l-arginine, while conjugated monomer and N-doping guaranteed bright fluorescence and relatively strong interactions between loaded cargos. Well-designed size allowed easy cell uptake of drug-loaded COFs, which finally resulted in a highly efficient starvation therapy by consuming large amounts of glucose in cancer cells. H2O2, the byproduct during glucose consumption, was made full use of oxidizing l-arginine to generate toxic NO. This constructed combined starvation and gas therapy and exhibited emerging antimigration performance. Both in vitro and in vivo experiments confirmed an excellent cancer therapeutic effect than a single therapy, and the novel therapeutic platform showed good biocompatibility. Detailed mechanism study demonstrated that cell apoptosis and lysosomal damage contributed most to the synergistic treatment. Our study developed a new strategy to synthesize highly conjugated COFs with fluorescence and reported the potential applications in cancer therapy.

Cerium Ammonium Nitrate-Mediated Access to Biaryl Lactones: Substrate Scopes and Mechanism Studies.

Herein we described an access to biaryl lactones from ortho-aryl benzoic acids via intramolecular O-H/C-H oxidative coupling with the commonly used cerium ammonium nitrate (CAN) as the one-electron oxidant under a thermal condition. The radical interrupting experiment suggested a radical process, while the kinetic isotope effect (KIE) showed that the C-H cleavage likely was not involved in the rate-determining step. Competitive reactions, especially the strikingly different ρ values of Hammett equations, indicated that the reaction rate was more sensitive to the electronic properties on the aryl moiety rather than the carboxylic moiety, which corresponded to the first single electron transfer (SET) step. In addition, the quite negative ρ values (-4.7) of the aryl moiety unveiled the remarkable electrophilic nature of the second intramolecular radical addition process, which was also consistent with product yields and regioselectivity. Moreover, control experiments disclosed that the single electron in the third step was also transferred to CeIV instead of molecular oxygen. Besides, the possible role of co-solvents trifluoroethanol (TFE) and its influences on the CeIV species were discussed. This work elucidated the possible mechanism by proposing the step that had more effects on the total reaction rate and the species that was responsible for the last single electron transfer.

Biomimetic synthesis of a novel O2-regeneration nanosystem for enhanced starvation/chemo-therapy.

Glucose oxidase-mediated starvation therapy that effectively cuts off energy supply holds great promise in cancer treatment. However, high glutathione (GSH) contents and anoxic conditions severely reduce therapy efficiency and cannot fully kill cancer cells. Herein, to resolve the above problem, this study constructed a biomimetic nanosystem based on nanreproo-MnO2with porous craspedia globose-like structure and high specific surface area, and it was further modified with dopamine and folic acid to guarantee good biocompatibility and selectivity toward cancer cells. This nanosystem responsively degraded and reacted with GSH and acid to regenerate O2, which significantly increased intracellular O2levels, accelerated glucose consumption, and improved starvation therapy efficiency. Moreover, anticancer drug of camptothecin was further loaded, and notably enhanced cancer growth inhibition was obtained at very low drug concentrations. Most importantly, this novel therapy could unprecedentedly inhibit cancer cell migration to a very low ratio of 19%, and detailed cell apoptosis analyses revealed late stage apoptosis contributed most to the good therapeutic effect. This work reported a new train of thought to improve starvation therapy in biomedicine, and provided a new strategy to design targeted nanocarrier to delivery mixed drugs to overcome the restriction of starvation therapy and develop new therapy patterns.

Catalyst-Free and Transition-Metal-Free Approach to 1,2-Diketones via Aerobic Alkyne Oxidation.

A catalyst-free and transition-metal-free method for the synthesis of 1,2-diketones from aerobic alkyne oxidation was reported. The oxidation of various internal alkynes, especially more challenging aryl-alkyl acetylenes, proceeded smoothly with inexpensive, easily handled, and commercially available potassium persulfate and an ambient air balloon, achieving the corresponding 1,2-diketones with up to 85% yields. Meanwhile, mechanistic studies indicated a radical process, and the two oxygen atoms in the 1,2-diketons were most likely from persulfate salts and molecular oxygen, respectively, rather than water.

Photocatalytic Asymmetric Epoxidation of Terminal Olefins Using Water as an Oxygen Source in the Presence of a Mononuclear Non-Heme Chiral Manganese Complex.

Photocatalytic enantioselective epoxidation of terminal olefins using a mononuclear non-heme chiral manganese catalyst, [(R,R-BQCN)MnII]2+, and water as an oxygen source yields epoxides with relatively high enantioselectivities (e.g., up to 60% enantiomeric excess). A synthetic mononuclear non-heme chiral Mn(IV)-oxo complex, [(R,R-BQCN)MnIV(O)]2+, affords similar enantioselectivities in the epoxidation of terminal olefins under stoichiometric reaction conditions. Mechanistic details of each individual step of the photoinduced catalysis, including formation of the Mn(IV)-oxo intermediate, are discussed on the basis of combined results of laser flash photolysis and other spectroscopic methods.