Scandium-Catalyzed Phenol-Directed Construction of 5-Carbonyl-4-hydroxybenzofurans via Intramolecular Friedel-Crafts Reaction.

Herein we report a scandium-catalyzed regioselective synthesis of 5-carbonyl-4-hydroxybenzofurans via a phenol-directed intramolecular Friedel-Crafts reaction. This synthetic method was applied for the total synthesis of furanoflavones. Experimental studies and density functional theory calculations suggest that hydrogen bond interactions between the phenolic hydroxy group and the scandium complex realize regioselective intramolecular cyclization.

A visible-light activated secondary phosphine oxide ligand enabling Pd-catalyzed radical cross-couplings.

Although transition metal-catalyzed reactions have evolved with ligand development, ligand design for palladium-catalyzed photoreactions remains less explored. Here, we report a secondary phosphine oxide ligand bearing a visible-light sensitization moiety and apply it to Pd-catalyzed radical cross-coupling reactions. The tautomeric phosphinous acid coordinates to palladium in situ, allowing for pseudo-intramolecular single-electron transfer between the ligand and palladium. Molecular design of the metal complexes aided by time-dependent density functional theory calculations enables the involvement of allyl radicals from π-allyl palladium(II) complexes, and alkyl and aryl radicals from the corresponding halides and palladium(0) complex. This complex enables radical cross-couplings by ligand-to-Pd(II) and Pd(0)-to-ligand single-electron transfer under visible-light irradiation.

Mechanistic Studies of the Pd- and Pt-Catalyzed Selective Cyclization of Propargyl/Allenyl Complexes.

Following the discovery of an unusual transition-metal-catalyzed reaction, the elucidation of the underlying mechanism is essential to understand the characteristic reactivity of the metal. We previously reported a synthetic method for tricyclic indoles using Pt-catalyzed Friedel-Crafts-type C-H coupling. In this reaction, the Pt catalyst selectively formed a seven-membered ring, but the Pd catalyst only afforded a six-membered ring. However, the reasons for the different selectivities caused by Pd and Pt were unclear. We performed density functional theory (DFT) calculations and experimental studies to reveal the origin of the different behaviors of the two metals. The calculations revealed that the formation of the six- and seven-membered rings proceeds via η1-allenyl and η3-propargyl/allenyl complexes, respectively. A molecular orbital analysis of the η3-propargyl/allenyl complex revealed that, for the platinum complex, the energy required to convert the unoccupied molecular orbital on the reactive carbon into the lowest unoccupied molecular orbital (LUMO) was lower than that for the palladium complex. In addition, DFT calculations revealed that the combination of platinum and bis[2-(diphenylphosphino)phenyl] ether (DPEphos) reduced the activation energy of the seven-membered cyclization in comparison with palladium or PPh3. Additional experimental studies, including NMR studies and stoichiometric reactions, support the aforementioned examination.

Py3-FITC: a new fluorescent probe for live cell imaging of collagen-rich tissues and ionocytes.

Polypyrrole-based polyamides are used as sequence-specific DNA probes. However, their cellular uptake and distribution are affected by several factors and have not been extensively studied in vivo. Here, we generated a series of fluorescence-conjugated polypyrrole compounds and examined their cellular distribution using live zebrafish and cultured human cells. Among the evaluated compounds, Py3-FITC was able to visualize collagen-rich tissues, such as the jaw cartilage, opercle and bulbus arteriosus, in early-stage living zebrafish embryos. Then, we stained cultured human cells with Py3-FITC and found that the staining became more intense as the amount of collagen was increased. In addition, Py3-FITC-stained HR cells, which represent a type of ionocyte on the body surface of living zebrafish embryos. Py3-FITC has low toxicity, and collagen-rich tissues and ionocytes can be visualized when soaked in Py3-FITC solution. Therefore, Py3-FITC may be a useful live imaging tool for detecting changes in collagen-rich tissue and ionocytes, including their mammalian analogues, during both normal development and disease progression.

Visible-Light-Induced Metal-/Photocatalyst-Free C-H Bond Imidation of Arenes.

In this study, a visible-light-induced intermolecular C-H bond imidation of arenes was achieved at ambient condition. By using simple phthalimide with (diacetoxyiodo)benzene and molecular iodine, direct metal-/photocatalyst-free C-N bond formation was achieved. The imidation protocol was designed by using time-dependent density functional theory calculations and experimentally demonstrated for 28 substrates with as high as 96% yield. Mechanistic studies indicated that radical-mediated aromatic substitution occurred via photolysis of N-iodophthalimide under visible-light irradiation.

A Direct S0 →Tn Transition in the Photoreaction of Heavy-Atom-Containing Molecules.

According to the Grotthuss-Draper law, light must be absorbed by a substrate to initiate a photoreaction. There have been several reports, however, on the promotion of photoreactions using hypervalent iodine during irradiation with light from a non-absorbing region. This contradiction gave rise to a mystery regarding photoreactions involving hypervalent iodine. We demonstrated that the photoactivation of hypervalent iodine with light from the apparently non-absorbing region proceeds via a direct S0 →Tn transition, which has been considered a forbidden process. Spectroscopic, computational, and synthetic experimental results support this conclusion. Moreover, the photoactivation mode could be extended to monovalent iodine and bromine, as well as bismuth(III)-containing molecules, providing new possibilities for studying photoreactions that involve heavy-atom-containing molecules.