Electrochemical Azo-free Mitsunobu-type Reaction.

The classic chemical Mitsunobu reaction suffers from the need of excess alcohol activation reagents and the generation of significant by-products. Efforts to overcome these limitations have resulted in numerous creative solutions, but the substrate scope of these catalytic processes remains limited. Here we report an electrochemical Mitsunobu-type reaction, which features azo-free alcohol activation and broad substrate scope. This user-friendly technology allows a vast collection of heterocycles as the nucleophile, which can couple with a series of chiral cyclic and acyclic alcohols in moderate to high yields and excellent ee's. This practical reaction is scalable, chemoselective, uses simple Electrasyn setup with inexpensive electrodes and requires no precaution to exclude air and moisture. The synthetic utility is further demonstrated on the structural modification of diverse bioactive natural products and pharmaceutical derivatives and its straightforward application in a multiple-step synthesis of a drug candidate.

Discovery of pyrazole N-aryl sulfonate: A novel and highly potent cyclooxygenase-2 (COX-2) selective inhibitors.

Based on a new pyrazole sulfonate synthetic method, a novel class of molecules with a basic structure of pyrazole N-aryl sulfonate have been designed and synthesized. The interest in conducting intensive research stems from quite evident anti-inflammatory effects exhibited by the compounds in preliminary animal experiments. A series of compounds were synthesized by different substitutions of the R1, R2, and R3 groups. Within the series, 4-iodophenyl 5-methyl-3-(p-tolyl)-1H-pyrazole-1-sulfonate and phenyl 5-methyl-3-(4-(trifluoromethyl) phenyl)-1H-pyrazole-1-sulfonate exhibited excellent anti-inflammatory activity (% inhibition of auricular edemas = 27.0 and 35.9, respectively); the in vivo analgesic activity of phenyl 5-methyl-3-(p-tolyl)-1H-pyrazole-1-sulfonate and 2-chlorophenyl 5-methyl-3-(p-tolyl)-1H-pyrazole-1-sulfonate was confirmed to be effective (inhibition ratio of writhing = 50.7% and 48.5% separately), and compounds phenyl 5-methyl-3-(p-tolyl)-1H-pyrazole-1-sulfonate , 4-iodophenyl 5-methyl-3-(p-tolyl)-1H-pyrazole-1-sulfonate and 2-chlorophenyl 5-methyl-3-(p-tolyl)-1H-pyrazole-1-sulfonate were identified as selective COX-2 inhibitors (SI = 455, 10,497 and >189 severally). In Acute Oral Toxicity assays conducted in vivo, the lethal dose 50 (LD50) of 4-iodophenyl 5-methyl-3-(p-tolyl)-1H-pyrazole-1-sulfonate and 2-chlorophenyl 5-methyl-3-(p-tolyl)-1H-pyrazole-1-sulfonate to mice was >2000 mg/kg BW.

Visible-light promoted regioselective amination and alkylation of remote C(sp3)-H bonds.

The C-N cross coupling reaction has always been a fundamental task in organic synthesis. However, the direct use of N-H group of aryl amines to generate N-centered radicals which would couple with alkyl radicals to construct C-N bonds is still rare. Here we report a visible light-promoted C-N radical cross coupling for regioselective amination of remote C(sp3)-H bonds. Under visible light irradiation, the N-H groups of aryl amines are converted to N-centered radicals, and are then trapped by alkyl radicals, which are generated from Hofmann-Löffler-Freytag (HLF) type 1,5-hydrogen atom transfer (1,5-HAT). With the same strategy, the regioselective C(sp3)-C(sp3) cross coupling is also realized by using alkyl Hantzsch esters (or nitrile) as radical alkylation reagents. Notably, the α-C(sp3)-H of tertiary amines can be directly alkylated to form the C(sp3)-C(sp3) bonds via C(sp3)-H - C(sp3)-H cross coupling through the same photoredox pathway.

Visible-Light-Promoted Dearomative Fluoroalkylation of ß-Naphthols through Intermolecular Charge Transfer.

The first visible-light-promoted dearomative fluoroalkylation of ß-naphthols was realized without the assistance of any transition-metal catalysts or external photosensitizers. Inexpensive fluoroalkyl iodides were directly used as efficient fluoroalkylation reagents under very mild reaction conditions. The scope of this process was found to be general and broad, and both trifluoromethyl and perfluoroalkyl groups (-C4 F9 , -C6 F13 , and -C8 F17 ) were installed in excellent yields. Preliminary mechanistic studies suggest that visible-light-promoted intermolecular charge transfer within the naphtholate-fluoroalkyl iodide electron donor-acceptor (EDA) complex induces a single electron transfer in the absence of photocatalysts.

Photoinduced, copper-catalyzed three components cyanofluoroalkylation of alkenes with fluoroalkyl iodides as fluoroalkylation reagents.

In the past few years, Ru and Ir catalyzed photoredox radical coupling reactions have been widely applied in organic synthesis. In contrast, the applications of Cu catalysts in photoredox organic transformations were limited. We here report the first example of photoinduced, Cu-catalyzed three component cyanofluoroalkylation of alkenes by directly using fluoroalkyl iodides as fluoroalkylation reagents.

Wild food plants and fungi used in the mycophilous Tibetan community of Zhagana (Tewo County, Gansu, China).

BACKGROUND: The aim of the study was to investigate knowledge and use of wild food plants and fungi in a highland valley in the Gannan Tibetan Autonomous Region on the north-eastern edges of the Tibetan Plateau. METHODS: Field research was carried out in four neighbouring villages in a mountain valley of the Diebu (Tewo) county, surrounded by spruce forests. The study consisted of 30 interviews with single informants, or group interviews (altogether 63 informants). Apart from collecting voucher specimens, we also identified fungi using DNA barcoding. RESULTS: We recorded the use of 54 species of vascular plants. We also recorded the use of 22 mushroom taxa, which made up the largest category of wild foods. Fruits formed the largest category of food plants, with 21 species, larger than the wild greens category, which consisted of 20 species eaten after boiling or frying and 7 as raw snacks. We also recorded the alimentary use of 10 species of edible flowers and 3 species with underground edible organs. On average, 20.8 edible taxa were listed per interview (median - 21). The most listed category of wild foods was green vegetables (mean - 7.5 species, median - 8 species), but fruits and mushrooms were listed nearly as frequently (mean - 6.3, median - 6 and mean - 5.8, - median 6 respectively). Other category lists were very short, e.g., flowers (mean - 1.3, median - 1) and underground edible parts (mean - 0.7, median - 1). Wild vegetables are usually boiled and/or fried and served as side-dishes, or their green parts are eaten as snacks during mountain treks (e.g., peeled rhubarb shoots). Wild fruits are mainly collected by children and eaten raw, they are not stored for further use. The most widely used wild staple foods are Potetilla anserina roots, an important ceremonial food served on such occasions as New Year or at funerals. They are boiled and served with sugar and butter. The most important famine plants remembered by people are the aerial bulbils of Persicaria vivipara. Flowers are used as children's snacks - their nectar is sucked. CONCLUSIONS: The number of wild taxa eaten in the studied valley is similar to that of other Tibetan areas. The structure of wild food plant taxa is also very typical for Tibetan speaking areas (e.g., the use of rhubarb shoots, Potentilla anserina, Persicaria vivipara). The studied community show a high level of mycophilia.

Silver-Catalyzed Difluoroamidation of Activated Alkenes for the Construction of Difluorinated 3,3-Disubstituted Oxindoles.

A AgOAc catalyzed difunctionalization of activated alkenes through a difluoroamidic radical addition to afford difluoroamidated 3,3-disubstituted oxindoles has been developed. Various functional groups were well tolerated. Moreover, the product could be efficiently derived to the corresponding difluorofunctionalized alcohol, ketone, and ester in high yields. The mechanistic studies revealed that a radical pathway was involved in the transformation.

Iodine(III)-Mediated Oxy-fluorination of Alkenyl Oximes: An Easy Path to Monofluoromethyl-Substituted Isoxazolines.

A highly regioselective intramolecular oxy-fluorination of alkenyl oximes was achieved. This new transformation represents an efficient method for the preparation of monofluoromethyl-substituted isoxazolines. The synthetic application of the oxy-fluorination product was demonstrated by a one-step synthesis of monofluoromethyl-substituted ß-hydroxyl ketone derivatives.

C-H bonds phosphorylation of ketene dithioacetals.

C-H bond phosphorylation of ketene dithioacetals was achieved under transition-metal-free or AgNO3 mediated conditions. Synthetic transformations of the coupling product provided promising methods for the construction of highly functionalized phosphorylated N-heterocycles and tetrasubstituted alkenes.

Copper-catalyzed intramolecular oxytrifluoromethylthiolation of unactivated alkenes.

A mild, versatile, and convenient method for efficient intramolecular oxytrifluoromethylthiolation of unactivated alkenes catalyzed by Cu(OAc)2 has been developed. The reactions were carried out under aerobic conditions and formed a variety of isoxazolines bearing a -SCF3 substituent.

Wild food plants used by the Tibetans of Gongba Valley (Zhouqu county, Gansu, China).

BACKGROUND: The ethnobotany of Tibetans is a seriously under-studied topic. The aim of the study was to investigate knowledge and use of wild food plants in a valley inhabited by Tibetans in the Gannan Tibetan Autonomous Region. METHODS: The field research was carried out in a wooded mountain valley in 9 neighbouring villages the Zhouqu (Brugchu) county, and comprised 17 interviews with single informants and 14 group interviews, involving 122 people altogether. RESULTS: We recorded the use of 81 species of vascular plants from 41 families. Fruits formed the largest category, with 42 species, larger than the wild greens category, with 36 species. We also recorded the culinary use of 5 species of edible flowers, 7 species with underground edible organs and 5 taxa of fungi. On average, 16.2 edible taxa were listed per interview (median - 16). Green vegetables formed the largest category of wild foods (mean - 8.7 species, median - 9 species), but fruits were listed nearly as frequently (mean - 6.9, median - 6). Other categories were rarely mentioned: flowers (mean - 0.2, median - 0), underground edible parts (mean - 0.3, median - 0) and mushrooms (mean - 1.5, - median 1).Wild vegetables are usually boiled and/or fried and served as side-dishes (cai). They are often lacto-fermented. Wild fruits are mainly collected by children and eaten raw, they are not stored for further use. The most widely used wild vegetables are: Eleuterococcus spp., Pteridium aquilinum, Helwingia japonica, Aralia chinensis, Allium victorialis, Pteridium aquilinum, Ixeris chinensis, Thlaspi arvense and Chenopodium album. The culinary use of Caltha palustris as a green vegetable is very interesting. In its raw state, marsh marigold is a toxic plant, due to the presence of protoanemonin. In this area it is dried or lactofermented before use. The most commonly eaten fruits are: Pyrus xerophila, Prunus salicina, Berchemia sinica, Rubus spp. and Eleagnus umbellata. CONCLUSIONS: The number of wild taxa eaten in the studied valley is relatively large compared to most studies from around the world. However, compared to the northern slope of the Qinling, in Shaanxi, the list is considerably shorter, in spite of the similar methodology applied and similar research effort involved.