Shigeru Arai
Verified @chiba-u.jp
Gradate School of Pharmaceutical Sciences
Chiba University
RESEARCH INTERESTS
Organic Synthesis, Heterocyclic Chemisytry, Catalysis, Natural Products, Total Synthesis
Scopus Publications
Scopus Publications
Nanaka Ishihara, Shinji Harada, Masaya Nakajima, and Shigeru Arai
American Chemical Society (ACS)
Here, we describe a unique reactivity of isatogen derivatives bearing a hydroxy group at the C3-position (isatogenol) and their synthetic application to highly regio- and stereoselective [3 + 2] cycloaddition reactions. This method provides facile access to polyfused and highly functionalized heterocycles including consecutive stereocenters. Furthermore, DFT calculations revealed that hydrogen bonding is a key to controlling the regio- and stereoselectivity in the cycloaddition using acrylates.
Shigeru Arai, Koichi Nakazawa, Xiao-Fei Yang, Masaya Nakajima, Shinji Harada, and Atsushi Nishida
Royal Society of Chemistry (RSC)
This work discloses the origin of regio- and stereoselectivity of hydrocyanation of alkynoates.
Ryoka Sakai, Nanaka Ishihara, Shinji Harada, and Shigeru Arai
Elsevier BV
Natsuki Ito, Shigeru Arai, and Atsushi Nishida
Wiley
AbstractWe report a reduction‐condensation‐1,3‐dipolar cycloaddition sequence to create C2‐C3 contiguous stereogenic centers in indoline derivatives. This method includes a one‐pot procedure starting from easily obtainable nitroketones and can be applied to intrarmolecular cycloaddition to give highly functionalized isoxazolidines. Both a length of methylene tether and olefinic substituents strongly affect the cycloaddition mode (exo/endo approach) to give highly stereo‐controlled tri‐ and tetracyclic systems through a single operation. Intermolecular cycloaddition is also applicable to the construction of 3 stereocenters in range of 47–87 % yield.
Shinji Harada, Shihori Sekino, Marisa Inaba, Ayumi Okita, Tetsuhiro Nemoto, Shigeru Arai, Hitomi Ohmagari, Miki Hasegawa, and Atsushi Nishida
American Chemical Society (ACS)
This study analyzes the feasibility of utilizing the catalytic and enantioselective [4 + 2] cycloaddition of sterically demanding heterocycle-incorporated siloxydienes to yield polycyclic skeletons with a tetrasubstituted carbon. A catalyst derived from lanthanide triflimide enabled the reaction. The mechanistic investigations and transformations of the adducts are also discussed. The proposed approach facilitates the synthesis of intricate polysubstituted skeletons, each with multiple contiguous chiral centers, thereby aiding in the production of diverse hydrocarbazoles for drug discovery purposes.
Shinji Harada, Juntaro Yamamoto, Akito Okabe, and Shigeru Arai
Wiley
AbstractWe report the synthesis of seven‐membered carbocycles through the dearomative intermolecular reaction of benzofurans with vinylcyclopropanes. The significant feature of this method involves activating benzofurans through energy transfer from an activated photocatalyst. Substituent effects were investigated for each substrate, and hydrocyclohepta[b]benzofurans with a tetrasubstituted carbon were obtained as a single diastereomer. This synthetic approach compliments the reported methodologies for synthesizing this type of skeleton and introduces a new feedstock for this skeleton with a different substitution pattern. Computational studies of the reaction mechanism suggested that the reaction proceeds stepwise through addition, small ring opening, and re‐cyclization. This novel synthetic approach opens up new possibilities for efficiently constructing seven‐membered carbocycles. Moreover, it provides a valuable platform for discovering unique molecules with diverse substitution patterns.
Shinji Harada, Ryotaro Koyama, Ryuya Masuda, and Shigeru Arai
Wiley
AbstractA trichloromethylative olefin lactonization reaction using an iridium photoredox catalyst was developed. The reactions proceeded at room temperature for olefins with various substituents and substitution patterns, and a variety of lactones with a tetrasubstituted carbon and trichloromethyl group were obtained regio‐ and stereoselectively. The reaction mechanism was elucidated through isotope labeling experiments. The chemical properties of the lactones containing the trichloromethyl groups were investigated, and synthetic transformations of the product were realized.
Shigeru Arai, Saki Inagaki, Masaya Nakajima, and Atsushi Nishida
Royal Society of Chemistry (RSC)
Vinylallenes have been recognized as versatile C2 and C4 components for nickel-catalyzed intramolecular [4+2] and [2+2] cycloadditions.
Yuna Kawata, Shigeru Arai, Masaya Nakajima, and Atsushi Nishida
Elsevier BV
Shigeru Arai and Atsushi Nishida
The Japan Institute of Heterocyclic Chemistry
Shigeru Arai, Yuichi Sato, Natsuki Ito, and Atsushi Nishida
Elsevier BV
Shigeru Arai, Arisa Izaki, Yuka Amako, Masaya Nakajima, Masanobu Uchiyama, and Atsushi Nishida
Wiley
Shigeru Arai, Yuna Kawata, Yuka Amako, and Atsushi Nishida
Elsevier BV
Shigeru Arai, Koichi Nakazawa, Xiao-fei Yang, and Atsushi Nishida
Elsevier BV
S. Arai, Koki Matsumoto and A. Nishida
H. Hori, S. Arai and A. Nishida
An efficient synthesis of carbo- and heterocycles using C[double bond, length as m-dash]C, C[double bond, length as m-dash]O and C[double bond, length as m-dash]N bonds under cobalt catalysis is described. The substituents on olefins are key for controlling the regio- and chemoselectivity in the initial hydrogen atom transfer step and quaternary carbons are efficiently constructed under mild conditions. Cyclopropane cleavage and tandem cyclization give highly functionalized bicyclic skeletons in a single operation.
Shigeru Arai
Pharmaceutical Society of Japan
Cyano (CN) groups are equivalent to carbonyl as well as amino- and hydroxymethyl groups. Therefore, their catalytic introduction under metal catalysis is an important issue in synthetic organic chemistry. Ni-catalyzed hydrocyanation is one of the most well-investigated, powerful tools for installing a CN group. However, it is still difficult to control chemo- and regioselectivity. In this review, the author uses allenes to enable regio-, stereo-, and face-selective transformations to natural product synthesis and axial chirality transfer.
Shigeru Arai, Yuka Amako, Hiroto Hori, and Atsushi Nishida
The Society of Synthetic Organic Chemistry, Japan
Koki Matsumoto, Shigeru Arai, and Atsushi Nishida
Elsevier BV
Shigeru Arai, Masaya Nakajima, and Atsushi Nishida
The Society of Synthetic Organic Chemistry, Japan
Hiroto Hori, Shigeru Arai, and Atsushi Nishida
Wiley
A nickel-catalyzed hydrocyanation triggered by hydronickelation of the carbon-carbon double bonds of allenes followed by cyclopropane cleavage is described. The observed regio- and stereochemistries in the products are strongly influenced by the initial hydronickelation step, and allenyl- and methylenecyclopropanes reacted smoothly to promote the cleavage of cyclopropane. In contrast, this cleavage was not observed with vinylidenecyclopropanes, because the initial hydronickelation does not give a suitable intermediate for cleavage of the cyclopropanes.
Shigeru Arai, Masaya Nakajima, and Atsushi Nishida
Elsevier
Yuka Amako, Shigeru Arai, and Atsushi Nishida
Royal Society of Chemistry (RSC)
The transfer of axial chirality of allenes is beginning to be exploited as a powerful method for creating central chirality, particularly through the use of transition metal catalysis.
Kazuyuki Tokumaru, Toshiyuki Ohfusa, Shigeru Arai, and Atsushi Nishida
Springer Science and Business Media LLC
Masaya Nakajima, Shigeru Arai, and Atsushi Nishida
Wiley
Enantioselective total syntheses of the Kopsia alkaloids (+)-grandilodine C and (+)-lapidilectine B were accomplished. A key intermediate, spirodiketone, was synthesized in 3 steps and converted into the chiral enone by enantioselective deprotonation followed by oxidation with up to 76 % ee. Lactone formation was achieved through stereoselective vinylation followed by allylation and ozonolysis. The total synthesis of (+)-grandilodine C was achieved by palladium-catalyzed intramolecular allylic amination and ring-closing metathesis to give 8- and 5-membered heterocycles, respectively. Selective reduction of a lactam carbonyl gave (+)-lapidilectine B. The absolute stereochemistry of both natural products was thereby confirmed. These syntheses enable the scalable preparation of the above alkaloids for biological studies.