Synthesizing Chiral Hydrocarbazoles with a Tetrasubstituted Carbon Using Holmium-Catalyzed Enantioselective [4 + 2] Cycloaddition: Mechanistic Insights from Luminescence and DFT Studies Shinji Harada, Shihori Sekino, Marisa Inaba, Ayumi Okita, Tetsuhiro Nemoto, et al. Journal of Organic Chemistry, 2024 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.
Isatogenols as Precursors for the Synthesis of Fully Substituted Indolines through Regio- and Stereoselective [3 + 2] Cycloaddition Using Various Olefins Nanaka Ishihara, Shinji Harada, Masaya Nakajima, Shigeru Arai Organic Letters, 2024 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.
Construction of C2-C3 Contiguous Stereogenic Centers in Indoline Derivatives by 1,3-Dipolar Cycloaddition Natsuki Ito, Shigeru Arai, Atsushi Nishida Asian Journal of Organic Chemistry, 2024 We 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.
Photocatalytic Dearomative Intermolecular Seven-Membered Ring Construction of Benzofurans Shinji Harada, Juntaro Yamamoto, Akito Okabe, Shigeru Arai Asian Journal of Organic Chemistry, 2023 We 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.
Trichloromethylative Olefin Lactonization by Photoredox Catalysis Shinji Harada, Ryotaro Koyama, Ryuya Masuda, Shigeru Arai European Journal of Organic Chemistry, 2023 A 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.
