Alkyne Insertion Enabled Vinyl to Acyl 1,5-Palladium Migration: Rapid Access to Substituted 5-Membered-Dihydrobenzofurans and Indolines.

"Through space" palladium/hydrogen shift is an efficient strategy to achieve selective functionalization of a specific remote C-H bond. Compared with relatively extensive exploited 1,4-palladium migration process, the relevant 1,5-Pd/H shift was far less investigated. We herein report a novel 1,5-Pd/H shift pattern between a vinyl and an acyl group. Through the pattern, rapid access to 5-membered-dihydrobenzofuran and indoline derivatives has been achieved. Further studies have unveiled an unprecedented trifunctionalization (vinylation, alkynylation and amination) of a phenyl ring through 1,5-palladium migration relayed decarbonylative Catellani type reaction. A series of mechanistic investigations and DFT calculations have provided insights into the reaction pathway. Notably, it was unveiled that the 1,5-palladium migration in our case prefers a stepwise mechanism involving a PdIV intermediate.

Pd-Catalyzed C(sp3)-H Biarylation via Transient Directing Group Strategy.

Here, we describe a highly selective Pd-catalyzed C(sp3)-H biarylation of 2-methylbenzaldehydes using cyclic diaryliodonium salts as arylation reagents. The key strategy is the employment of tert-leucine as a bidentate transient directing group for the proximity-driven metalation to achieve reactivity and selectivity in C-H activation. Various functionalized biaryls bearing both aldehyde and iodine functional groups were prepared successfully, which could be further transformed into a wide range of compounds with potential applications in pharmaceutical chemistry and materials science.

Enantiospecific electrochemical rearrangement for the synthesis of hindered triazolopyridinone derivatives.

Triazolopyridinone derivatives are of high value in both medicinal and material chemistry. However, the chiral or hindered triazolopyridinone derivatives remain an underexplored area of chemical space because they are difficult to prepare via conventional methods. Here we report an electrochemical rearrangement for the efficient synthesis of otherwise inaccessible triazolopyridinones with diverse alkyl carboxylic acids as starting materials. This enables the efficient preparation of more than 60 functionalized triazolopyridinones under mild conditions in a sustainable manner. This method is evaluated for the late stage modification of bioactive natural products, amino acids and pharmaceuticals, and it is further applied to the decagram scale preparation of enantiopure triazolopyridinones. The control experiments support a mechanism involving an oxidative cyclization and 1,2-carbon migration. This facile and scalable rearrangement demonstrates the power of electrochemical synthesis to access otherwise-inaccessible triazolopyridinones and may find wide application in organic, material and medicinal chemistry.

A Tandem Oxidative Annulation Strategy for the Synthesis of Tetracyclic 3-Spirooxindole Benzofuranones.

A simple and efficient method was developed for the construction of the medicinally important tetracyclic 3-spirooxindole benzofuranones. In this highly atom- and step-economical one-pot protocol, one quaternary carbon center, two new cycles, and four new bonds (C-C/C-O/C-N) were formed under simple ligand-free copper-catalyzed conditions through a novel tandem oxidative annulation strategy.

Synthesis of Functionalized Biaryls and Poly(hetero)aryl Containing Medium-Sized Lactones with Cyclic Diaryliodonium Salts.

A novel one-pot procedure is described for the transition-metal catalyzed sequential difunctionalization of diaryliodonium reagents. Reaction of commercially available anthranilic acid derivatives with readily available cyclic diaryliodonium salts followed by a Sonogashira coupling afforded various alkyne substituted biaryls in good to excellent yields. The functionalized biaryls were then utilized for the rapid and efficient one-pot synthesis of novel poly(hetero)aryl containing 10-membered lactones which are potential G-quadruplex binders and telomerase inhibitors.

Copper-Catalyzed Selective Diphenylation of Carboxylic Acids with Cyclic Diaryliodonium Salts.

Herein, we describe a novel one-step copper-catalyzed diphenylation of readily available aliphatic or (hetero)aromatic carboxylic acids with cyclic hypervalent diaryliodonium reagents. The selective diphenylation of benzoic acids with high atom economy can be achieved without observation of the arylation at the phenyl hydroxyl/thio/amino position. The valuable biphenyl esters with an additional iodo-substituent were obtained in good to excellent yields, which can be further transformed to diversified building blocks for the synthesis of bioactive natural products, pharmaceuticals, and functional materials. A wide range of different functional groups are compatible under the optimized reaction conditions.

The H+/K+-ATPase inhibitory activities of Trametenolic acid B from Trametes lactinea (Berk.) Pat, and its effects on gastric cancer cells.

Trametenolic acid B (TAB), the bioactive component in the Trametes lactinea (Berk.) Pat, was reported to possess cytotoxic activities and thrombin inhibiting effects. This study was performed to investigate the effects of TAB on H(+)/K(+)-ATPase and gastric cancer. The H(+)/K(+)-ATPase inhibitory activity was determined by gastric parietal cells. Compared to the normal control group, TAB (10, 20, 40 and 80 µg/mL) inhibited the H(+)/K(+)-ATPase activity by 15.97, 16.96, 24.86 and 16.25%, respectively. In the study, 36 Kunming mice were randomly divided into six groups: control, model, TAB-L (TAB, 5 mg/kg/day, i.g.), TAB-M (TAB, 20 mg/kg/day, i.g.), TAB-H (TAB, 40 mg/kg/day, i.g.) and omeprazole (OL, 10 mg/kg/day, i.g.). All mice except the control group were administrated with anhydrous alcohol (5.0 mL/kg, i.g.) for induced gastric-ulcer 1h after the 5th day. At the same time, the control mice were given the same volume of physiological saline. After 4h, TAB was evaluated for H(+)/K(+)-ATPase inhibitory activities of ulcerative gaster, gastric ulcer index and ulcer inhibition. In vitro, the anti-proliferation effect of TAB to gastric cancer cell (HGC-27) in acid environment was detected by MTT, and the apoptosis morphological changes were also observed by Hoechst 33258 dye assay. The results indicated that TAB inhibited moderately H(+)/K(+)-ATPase activity in vitro. Compared to the model group, TAB showed anti-ulcer effects in gastric tissue with the dosages of 20 and 5 mg/kg in vivo. Apart from that, TAB could selectively inhibit gastric cancer cell viability and reduce cell apoptosis against HGC-27 cells at low doses in acid environment.

(2S*,3S*,3aS*,6S*,7aR*)-3-Hy-droxy-2-[(2R*,3S*)-3-isopropyl-oxiran-2-yl]-3,6-dimethyl-3,3a,5,6,7,7a-hexa-hydro-1-benzofuran-4(2H)-one.

In the title compound, C(15)H(24)O(4), the six-membered ring shows a distorted chair conformation and the five-membered ring adopts an envelope conformation with the C atom bearing the methyl and OH groups as the flap. In the crystal, O-H⋯O hydrogen bonds link the mol-ecules into chains running along the a-axis direction.