Abstract The palladium‐catalyzed reaction of aromatic amides with maleimides results in the formation of a double C−H bond activation product, which occurs at both the benzylic and meta positions. Computational chemistry studies suggest that the first C−H bond activation unfolds via a six‐membered palladacycle, maleimide insertion, protonation of the Pd−N bond, and then activation of the meta C−H bond. The process concludes with reductive elimination, producing an annulation product. The energy decomposition analysis (EDA) showed that the deformation energy favors the ortho C−H bond activation process. However, this route is non‐productive. The interaction energy controls the site where the maleimide is inserted into the Pd−C(sp³) bond, which determines its site selectivity. The energetic span model indicates that the meta C−H bond activation step is the one that determines the turnover frequency. Regarding the directing group, it has been concluded that the strong Pd−S bonding and the destabilizing effect of the deformation energy allow the 2‐thiomethylphenyl to function effectively as a directing group.

Abstract The transformation of cyclobutanones into acyclic carbonyl compounds through a Pd-catalyzed C–C bond cleavage is reported. The use of an N-heterocyclic carbene ligand efficiently promoted the ring opening and functionalization of various cyclobutanones, not only with alcohols, but also with N-centered nucleophiles, such as aniline or amide derivatives. Cyclobutanones were also found to react with arylboronic esters, resulting in the production of acyclic aryl ketones.

Nucleophilic aromatic substitution (S_NAr) reactions of non-activated aryl fluorides with amide enolates are reported. DFT calculations suggest that the reaction proceeds through a concerted S_NAr pathway.

A palladium-catalyzed reaction of N-phthaloyl hydrazones derived from aldehydes and cyclobutanones, leading to the production of nitriles, is described.

DYASIN of racemic dynamic chiral heterohelicenes afforded their highly enantioenriched forms in quantitative yields. These heterohelicenes were readily converted into semi-static axial-chiral 1,1′-binaphthyl derivatives in a stereospecific manner.

The first Pd-catalyzed 1,1-alkynylbromination of terminal alkenes using alkynyl bromides, which provides direct access to a variety of functionalized propargylic bromides without the need for an external brominating reagent, is reported.

Copyright © 2020 American Chemical Society. During the past decades, synthetic organic chemistry discovered that directing group assisted C-H activation is a key tool for the expedient and siteselective construction of C-C bonds. Among the various directing group strategies, bidentate directing groups are now recognized as one of the most efficient devices for the selective functionalization of certain positions due to fact that its metal center permits fine, tunable, and reversible coordination. The family of bidentate directing groups permit various types of assistance to be achieved, such as N,N-dentate, N,O-dentate, and N,S-dentate auxiliaries, which are categorized based on the coordination site. In this review, we broadly discuss various C-H bond functionalization reactions for the formation of C-C bonds with the aid of bidentate directing groups.

The Ni-catalyzed reaction of aromatic amides with alkynes in the presence of KOBut involves C-H/N-H oxidative annulation to give 1(2H)-isoquinolinones. A key to the success of the reaction is the use of a catalytic amount of strong base, such as KOBut. The reaction shows a high functional group compatibility. The reaction with unsymmetrical alkynes, such as 1-arylalkynes, gives the corresponding 1(2H)-isoquinolinones with a high level of regioselectivity. This discovery would lead to the development of Ni-catalyzed chelation-assisted C-H functionalization reactions without the need for a specific chelation system.

Axially chiral biaryl units are key components of natural products and biologically active compounds as well as chiral molecular catalysts, and thus significant efforts have been focused on the efficient synthesis of atropisomerically enriched axially chiral biaryls. Among a variety of strategies, dynamic kinetic resolution is considered as an efficient method in asymmetric synthesis since highly enantio-enriched products could be furnished in quantitative yields from racemic starting materials in the best case. This review highlights recent progress of dynamic kinetic asymmetric transformations of racemic axially chiral biaryls by using transition-metal catalysts.

In this research, activation methods for nitrogen-nitrogen bonds and their application for organic synthesis were investigated. As a result, the palladium/N-heterocyclic carbene-catalyzed transformation of hydrazones into nitriles was developed. This transformation involves the cleavage of a nitrogen-nitrogen bond of hydrazones to provide nitrile moiety. In addition, new reactions catalyzed by various palladium complexes have been developed during this research. These results would be helpful for future research regarding direct molecular transformations.

In this study, design and synthesis of dynamic planar-chiral cyclic amines were carried out. The stereochemical analysis of newly obtained planar-chiral cyclic amines revealed that they can be racemized rapidly at room temperature. Control of their dynamic stereochemical behavior by using intramolecular hydrogen bond or coordination of metal complexes were also examined. In addition, stereospecific transformation methods of optically active planar-chiral cyclic amines to central chiral molecules were developed. For example, transannular reaction with strong base and epoxidation proceeded stereospecifically. Furthermore, enantioselective synthesis of planar chiral cyclic amines was accomplished based on the Pd-catalytzed asymmetric cyclization reaction.

有機強酸として知られるスクアリン酸は、2つのカルボニル基と2つの酸性プロトンを対称に有するため、水素結合の受容体あるいは供与体として振る舞うことのできる化合物である。本研究では、スクアリン酸のユニークな構造的特徴を活用したブレンステッド触媒の開発と、その有機合成反応への応用を目的としている。今年度は、触媒合成法の確立と適用可能な有機反応の探索に関して検討を行った。 スクアリン酸アミド触媒は、スクアリン酸ジメチルに対し、側鎖に用いるアミンとトリフルオロメタンスルホンアミドを逐次的に導入することで合成できる。トリフルオロメタンスルホンアミドの導入には、1当量のジブチルマグネシウムの添加が必要であることがわかった。 得られた触媒をα―ベンゾイルラクトンの加水分解反応に用いたところ、目的の反応に続いて脱炭酸が進行し、対応するアルコール生成物が得られた。一方、メタノール中で同様の反応を行うと、対応するメチルエステルが得られることがわかった。他のエステルの加水分解も試みたが、触媒活性は見られなかった。 スクアリン酸アミド触媒と金属試薬を組み合わせた不斉反応の検討も行ったところ、ケトン類のボラン還元において不斉誘起が確認された。また、不斉誘起にはヒドロキシ基の酸性プロトンが必須であることがわかった。 以上のように、スクアリン酸アミド触媒はエステルの加水分解やケトンの不斉還元などの有機合成反応に一定の効果を持つこと明らかになった。従来のスクアリン酸アミド触媒にはない強酸性プロトンが、カルボニル基の活性化に寄与することが示唆される。

炭素-水素結合は有機化合物に普遍的に見られる化学結合である。この結合を選択的に切断し、新たな化学結合形成に利用する研究は、天然資源に乏しいわが国において効率的な化学合成プロセスの構築につながる重要な研究である。これまでに金属触媒に対して配位可能なヘテロ原子を有する配向基を利用した、ベンゼン誘導体とプロモアセチレンの直接クロスカップリング反応がパラジウム触媒により進行することを見出している。今回、複数の配位点を持つ配向基として、8-アミノキノリンや2-ピリジニルメチルアミン由来のアミド基を用いた直接アルキニル化反応を前年度に引き続き検討した。その結果、添加剤として酢酸セシウムを用いると、良好な収率で芳香族オルト位炭素-水素結合の直接アルキニル化が進行した。また、これまで適用が困難であった電子不足性置換基を有する安息香酸アミドであっても効率良く反応が進行した。 さらに、同じ配向基を利用してより反応性の乏しい炭素-水素結合を有する脂肪族カルボン酸アミドのアルキニル化反応を検討したところ、添加剤に酢酸銀と塩化リチウムを用いることでアミドのβ-位の直接アルキニル化が良好な収率で進行した。アミノ酸誘導体や胆汁酸などの生物由来のカルボン酸アミドのアルキニル化に対してもが可能であり、生体内分子の修飾に有効であることがわかった。 一方、パラジウム触媒では適用が困難であった含窒素複素環を配向基とする芳香族化合物の直接アルキニル化が、ルテニウム触媒により進行することがわかった。本触媒系ではピバル酸セシウムが効果的な添加剤であり、ピリジンやピリミジン、ピラジンなど様々な窒素配向基が適用可能であった。また、活性水素を持つイミダゾールを有する基質でも良好な収率でアルキニル化体を与えた。したがって、配向基と金属触媒を適切に選択することで新たな反応性を見出すことが期待できる。