Palladium-Catalyzed Cascade Endo-dig Cycloisomerization and Olefination with Alkenes to Access Fused Oxatricyclic Compounds.

A novel cascade Pd(II)-catalyzed endo-dig cycloisomerization and olefination reaction of 2-benzyl-3-alkynyl chromones with activated/unactivated alkenes has been developed for the synthesis of fused oxatricyclic compounds. This concise one-pot synthetic approach was applied to the difunctionalization of unbiased alkynes based on 2-benzyl-3-(alkynyl)-4H-chromen-4-one via O-attack endo-dig cycloisomerization, followed by olefination with both activated and unactivated alkenes.

Palladium-Catalyzed Chemo- and Regiocontrolled Tandem Cyclization/Cross-Coupling of 2-Benzyl-3-alkynyl Chromones with Aryl Iodides for the Synthesis of 4H-Furo[3,2-c]chromenes and Xanthones.

A novel Pd-catalyzed chemo- and regiocontrolled tandem cyclization/cross-coupling reaction of 3-alkynyl chromone with aryl iodide was developed for the synthesis of 4H-furo[3,2-c]chromenes and xanthones. The difunctionalization of alkynes through O-attack/5-exo-dig and C-attack/6-endo-dig cyclization was reported by this rare approach, which was selectively controlled by the addition of KF or a bidentate phosphine ligand. A one-pot tandem process was demonstrated directly from γ-alkynyl-1,3-diketone for this method.

Pd-Catalyzed and ligand-enabled alkene difunctionalization via unactivated C-H bond functionalization.

Palladium-catalyzed and ligand-enabled C-H functionalization methods have emerged as a powerful approach for the preparation of therapeutically important motifs and complex natural products. Olefins, owing to their natural abundance, have been extensively employed for the formation of C-C and C-X bonds and the generation of various heterocycles. Traditionally, activated as well as starting materials with preinstalled functional groups, and also halide substrates under transition metal catalysis, have been employed for olefin difunctionalization. However, strategies for employing unactivated C-H bond functionalization to achieve alkene difunctionalization have rarely been explored. A possible solution to this challenge is the application of bulky ligands which enhances the reductive elimination pathway and inhibits ß-hydride elimination to selectively yield difunctionalized alkene products. This feature article summarizes the utilization of unreactive C-H bonds in the Pd-catalyzed and ligand-enabled difunctionalization of alkenes.

Synthesis, biological evaluation, and correlation of cytotoxicity versus redox potential of 1,4-naphthoquinone derivatives.

A series of 1,4-naphthoquinone derivatives of lawsone (1), 6-hydroxy-1,4-naphthoquinone (2), and juglone (3) were synthesized by alkylation, acylation, and sulfonylation reactions. The yields of lawsone derivatives 1a-1k (type A), 6-hydroxy-1,4-naphthoquinone derivatives 2a-2j (type B), and juglone derivatives 3a-3h (type C) were 52-99%, 53-96%, and 28-95%, respectively. All compounds were tested in vitro for the cytotoxicity against human oral epidermoid carcinoma (KB) and cervix epithelioid carcinoma (HeLa) cells and their structure-activity relationship was studied. Compound 3c was found to be most potent in KB cell line (IC50 = 1.39 µM). Some compounds were evaluated for DNA topoisomerase I inhibition. Compounds 2c, 3, 3a, and 3d showed topoisomerase inhibition activity with IC50 values of 8.3-91 µM. Standard redox potentials (E°) of all naphthoquinones in phosphate buffer at pH 7.2 were examined by means of cyclic voltammetry. A definite correlation has been found between the redox potentials and inhibitory effects of type A compounds.

Copper-catalyzed oxidative coupling of formamides with salicylaldehydes: synthesis of carbamates in the presence of a sensitive aldehyde group.

A diverse library of novel carbamates was synthesized utilizing copper-catalyzed oxidative C-O coupling of formamides and salicylaldehydes. Sensitive aldehyde groups remained intact in the presence of an oxidant and a transition-metal salt. Salicylaldehydes bearing electron-donating, electron-withdrawing, and halogen groups as well as 1-hydroxy-2-naphthaldehydes provided the desired carbamates in good to excellent yields.

Iron-catalyzed oxidative direct α-C-H bond functionalization of cyclic ethers: selective C-O bond formation in the presence of a labile aldehyde group.

Iron catalyzed oxidative coupling of salicylaldehydes with cyclic ethers proceeded through the direct α-C-H functionalization of ethers, forming the corresponding acetals in moderate to excellent yields. This is the first example of iron catalyzed selective C-O bond formation in the presence of a sensitive aldehyde moiety.

Insights on the isolation, biological activity and synthetic protocols of enyne derivatives.

Enyne derivatives isolated from terrestrial plants and fungi have recently attracted attention due to their interesting biological activities. It was found that these derivatives possess in general potent antiinflammatory activity which was attributed to the structural similarity of enynes with the natural antiinflammatory agents secreted in the human body. The biosynthesis of some of the isolated enynes has been proposed based on detailed isotope labeling studies. Computational calculations have been utilized to analyze the conformational preferences and forces affecting interaction of some enynes with the target binding sites. Synthesis of enynes has been achieved using several coupling techniques. In the current review we shed some light on the isolation, biological activity, and biosynthetic routes of enynes. We also recount different synthetic methodologies developed for the synthesis of compounds containing enyne functional group.