Identification of the Optimal Framework for Nitroxyl Radical/Hydroxylamine in Copper-Cocatalyzed Aerobic Alcohol Oxidation

Masaki Toda; Yusuke Sasano; Masaya Takahashi; Shogo Fujiki; Koki Kasabata; Tetsuya Ono; Katsuhiko Sato; Yoshitomo Kashiwagi; Yoshiharu Iwabuchi

doi:10.1021/acs.joc.2c02327

Identification of the Optimal Framework for Nitroxyl Radical/Hydroxylamine in Copper-Cocatalyzed Aerobic Alcohol Oxidation

J Org Chem. 2023 Feb 3;88(3):1434-1444. doi: 10.1021/acs.joc.2c02327. Epub 2023 Jan 19.

Authors

Masaki Toda¹, Yusuke Sasano¹, Masaya Takahashi¹, Shogo Fujiki¹, Koki Kasabata¹, Tetsuya Ono², Katsuhiko Sato³, Yoshitomo Kashiwagi², Yoshiharu Iwabuchi¹

Affiliations

¹ Graduate School of Pharmaceutical Sciences, Tohoku University; 6-3 Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan.
² School of Pharmaceutical Sciences, Ohu University, 31-1 Misumido, Tomita-machi, Koriyama, Fukushima 963-8611; Japan.
³ Faculty of Pharmaceutical Science, Tohoku Medical and Pharmaceutical University; 4-4-1 Komatsushima, Aoba, Sendai 981-8558, Japan.

PMID: 36655914
DOI: 10.1021/acs.joc.2c02327

Abstract

8-Azabicyclo[3.2.1]octan-8-ol (ABOOL) and 7-azabicyclo[2.2.1]heptan-7-ol (ABHOL) are the main homologues of hydroxylamine 2-azaadamantan-2-ol (AZADOL) and 9-azabicyclo[3.3.1]nonan-9-ol. Both homologues feature a small bicyclic backbone and are known to be stable; however, to date, they have not been used as catalysts for alcohol oxidation. Herein, we report that these hydroxylamines can efficiently catalyze the oxidation of various secondary alcohols to their corresponding ketones using molecular oxygen in ambient air as the terminal oxidant and copper cocatalysts at room temperature. Furthermore, we show that ABOOL and ABHOL can be easily synthesized from commercially available materials.