Formation of Isolable Dearomatized [4 + 2] Cycloadducts from Benzenes, Naphthalenes, and N-Heterocycles Using 1,2-Dihydro-1,2,4,5-tetrazine-3,6-diones as Arenophiles under Visible Light Irradiation

Kazuki Ikeda; Riku Kojima; Kentaro Kawai; Takayasu Murakami; Takashi Kikuchi; Masahiro Kojima; Tatsuhiko Yoshino; Shigeki Matsunaga

doi:10.1021/jacs.3c02556

Formation of Isolable Dearomatized [4 + 2] Cycloadducts from Benzenes, Naphthalenes, and N-Heterocycles Using 1,2-Dihydro-1,2,4,5-tetrazine-3,6-diones as Arenophiles under Visible Light Irradiation

J Am Chem Soc. 2023 Apr 26;145(16):9326-9333. doi: 10.1021/jacs.3c02556. Epub 2023 Apr 13.

Authors

Kazuki Ikeda¹, Riku Kojima¹, Kentaro Kawai¹, Takayasu Murakami¹, Takashi Kikuchi², Masahiro Kojima¹, Tatsuhiko Yoshino^{1

3}, Shigeki Matsunaga^{1

3}

Affiliations

¹ Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
² Rigaku Corporation, 3-9-12 Matsubara-cho, Akishima-shi, Tokyo 196-8666, Japan.
³ Global Station for Biosurfaces and Drug Discovery, Hokkaido University, Kita-12 Nishi-6, Kita-ku, Sapporo 060-0812, Japan.

PMID: 37055373
DOI: 10.1021/jacs.3c02556

Abstract

We report that the dearomative [4 + 2] cycloaddition between 1,2-dihydro-1,2,4,5-tetrazine-3,6-diones (TETRADs) and benzenes, naphthalenes, or N-heteroaromatic compounds under visible light irradiation affords the corresponding isolable cycloadducts. Several synthetic transformations including transition-metal-catalyzed allylic substitution reactions using the isolated cycloadducts at room temperature or above were demonstrated. Computational studies revealed that the retro-cycloaddition of the benzene-TETRAD adduct proceeds via an asynchronous concerted mechanism, while that of the benzene-MTAD adduct (MTAD = 4-methyl-1,2,4-triazoline-3,5-dione) proceeds via a synchronous mechanism.