論文種別：

　総合論文

論文題名：

　縮環π拡張（APEX）反応による多環芳香族化合物の精密合成

著者：

　伊藤英人^＊，松岡 和，矢野裕太，柴田万織，伊丹健一郎^＊

掲載誌：

　有機合成化学協会誌第78巻7号pp671-682　2020

論文取り下げの理由：

　総合論文中で引用している原著論文が取り下げられたため，著者の申し出により当該論文を取り下げる。

［n］Circulenes belong to a class of polycyclic aromatic hydrocarbon (PAH) having an n-membered ring at the center. Encouraged by recent advancements in heteronanographene chemistry, we have explored novel hetero［8］circulenes and related molecules with exceptional properties and functions. As the first synthetic target, tetraaza［8］circulene was designed in conjunction with our interests in the 8π antiaromaticity of porphyrin sheet. Tetrabenzotetraaza［8］circulene was successfully synthesized by fold-in type oxidative fusion reaction in a good yield. It is revealed that the central cyclooctatetraene (COT) unit in this molecule did not exhibit antiaromatic characteristics. This molecule rather behaves as a highly fluorescent molecule like typical aromatic fluorophores. The optical property can be further tuned by N-alkylation reactions. In relation with the developed synthetic protocol, quasi-aza［8］circulenes, triazaoxa［8］circulene, and azahelicenes were synthesized and characterized. In most cases, good solubility in hydrogen-bond accepting solvents such as acetone and THF represented a notable feature in these molecules, contrary to usual large PAHs that are insoluble in these solvents. Unexpected helicene forming reactions were found upon oxidation of ortho-phenylene-bridged cyclic hexapyrrole and hexathiophene. Finally, attempts toward the formation of a tribenzotriazasumanene skeleton were made, that resulted in the formation of partly fused products under both oxidative and reductive conditions.

Formation of monosubstituted vinylidenes from terminal alkynes at metal complexes as well as its mechanisms has been well studied, and this process is now recognized as a powerful and reliable method for the activation of terminal alkynes in organic chemistry. In contrast, the formation of disubstituted vinylidenes from carbon-based internal alkynes via 1,2-migration of a carbon substituent remained elusive. In this article, we describe our studies on the vinylidene rearrangement of common internal alkynes at group 8 metal complexes and its application to organic synthesis. Anionic and cationic group 8 metal complexes can affect the vinylidene rearrangement of carbon-substituted internal alkynes via the 1,2-migration of aryl and alkyl groups. The migratory aptitude of aryl groups was investigated experimentally and theoretically, and the results reveal that, unlike the general nucleophilic rearrangements, the less-electron-donating aryl group preferentially migrates as the nucleophile in the vinylidene rearrangement. This vinylidene rearrangement using a cationic ruthenium complex was successfully applied for catalytic transformations of 2-alkynylaniline, 3-amino-4-alkynylcoumarin, and 2-alkynylstyrene derivatives that lead to 3-substituted indole, 1-arylpyrrolocoumarin, and 1-disubstituted naphthalene derivatives, respectively.

Fluorine-containing amino acids have attracted considerable recent attention, owing to their potential application in widespread scientific fields. To date, several types of fluorinated α- and β-amino acids have been studied, whose characteristics change dramatically depending on the position of fluorine atoms. Among them, γ-fluorinated α-amino acids and γ-fluorinated β-amino acids are of particular importance, because they serve as suitable components for peptide-bond formation, because of their stability, tolerance toward racemization, and proper reactivity. By incorporating these fluorinated amino acids into peptides and proteins, their structures and functions can be analyzed and controlled in a rational way. At present, however, stereoselective synthesis of these fluorinated amino acids still remains a challenge. We have developed highly practical asymmetric synthesis of ᴅ-4,4,4-trifluoro-allo-threonine and (S)-3-trifluoromethyl-β-alanine. Each of them can be synthesized in a stereopure form and in a large scale without using any expensive reagent and special apparatus. In particular, the synthesis of (S)-3-trifluoromethyl-β-alanine does not require column chromatography for the purification process of all steps. By using (R)-3-trifluoromethyl-β-alanine as a component of peptides, we also investigated the effects of the attachment of CF₃ groups to the backbone of an oligo-β-peptides that tend to adopt a 14-helix structure. Our systematic studies revealed that the attachment of CF₃ groups to the peptide backbones enhances the hydrogen-bonding ability of the NH groups adjacent to the CF₃ groups, so that the 14-helix structure of the oligo-β-peptides was significantly stabilized.

In plants, there are several kinds of intercellular signal transduction systems, such as with phytohormones and with peptide hormones. Small post-translationally modified peptides, which act as cell-to-cell signaling molecules, constitute the largest group of peptide hormones with various functions in intercellular signal transductions. We explored peptide hormones by in silico gene screening coupled with biochemical peptide detection. We also identified specific direct ligand-binding receptors for these peptides. In general, receptor genes are highly redundant in Arabidopsis and thus it is often difficult to identify the specific receptors by using classical forward and reverse genetics. To overcome this problem, we identify peptide hormone receptors by detecting direct peptide hormone-receptor interaction using photoaffinity labeling with photoactivatable peptide derivatives and custom-made receptor library. This review summarizes how we discovered these peptide hormone-receptor pairs and how these pairs function in plant growth and development.

Although arene hydrogenation is one of the most straightforward reactions to access saturated cyclic compounds, there were huge limitations mostly due to undesired hydrodefunctionalization reactions. This review focuses on recent developments of catalytic arene hydrogenation with high functional tolerance.

The catalysts for the synthesis of formic acid from CO₂ and H₂ have been energetically studied. In recent years, formic acid synthesis reactions using non-precious metal complexes as catalysts are attracting attention from the viewpoint of environmental harmony and economy. This short review describes recent studies of catalysts for the synthesis of formic acid form CO₂ and H₂ without using precious metals: (1) phosphine free iron complexes catalyst combined with MOF, (2) transition metal free B(C₆F₅)₃ catalysts.

Quinonemethides (QM) are reactive chemical species which can be generated from o- and p-hydroxy benzyl alcohol derivatives even in aqueous media. Its unique reactivity is frequently utilized in organic synthesis and chemical biology. The high electrophilicity of QM would result in the rapid formation of a covalent bond with nucleophilic amino-acid residues in peptide or nucleic-acid bases. In addition, released leaving groups in the formation of QM can be designed as, for example, bioactive molecules for drug-delivery system and fluorophores for activity-based probe. Herein, recent reports associated with the quinonemethide chemistry are described.