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

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.

Electrochemical Characterization of a Novel Organoelectrocatalyst, 7-Azabicyclo[2.2.1]heptan-7-ol (ABHOL), and Its Application to Electrochemical Sensors

“…11) ABHOL had better performance as an electrochemical probe than AZADO because of its more compact bicyclic structure, which reduces steric hindrance around the nitroxyl radical moiety. 23) In addition, the high oxidation potential may have contributed to the high peak current. The proposed electrochemical reaction of ABHOL based on these results is shown in Chart 1.…”

“…In contrast, although ABHOL requires a six-step synthesis, the starting material, trans-4-aminoyclohexanol, is relatively cheap, and several of the steps are simple reactions, such as protection-deprotection, and have high yields, making ABHOL suitable for use as a general-purpose analytical probe. 23)…”

“…Experimental Materials ABNO 19) and ABHOL 23) were synthesized according to the literature. TEMPO was purchased from TCI.…”

“…[9][10][11][12][13] We reported that 7-azabicyclo[2.2.1] heptan-7-ol (ABHOL), a highly active hydroxylamine catalyst with a new structure, exhibits high catalytic activity for alcohol oxidation under aerobic oxidation conditions using a copper salt as a co-catalyst. 23) ABHOL is oxidized to the corresponding nitroxyl radical (7-azabicyclo[2.2.1] heptane N-oxyl; ABHO) under oxidation reaction conditions and exhibits oxidation catalytic activity. ABHOL was synthesized in six steps from trans-4-aminocyclohexanol (32.00 USD/25 g from TCI America), which is cheaper than nortropine (103.00 USD/25 g from TCI America), the starting material for 3-HO-ABOO.…”

Oxidative Deprotection of Benzyl Protecting Groups for Alcohols by an Electronically Tuned Nitroxyl-Radical Catalyst

“…Nitroxyl radicals such as 2,2,6,6-tetramethylpiperidine N -oxyl (TEMPO), 2-azaadamantane N -oxyl (AZADO), and their derivatives are well-known and highly chemoselective oxidation catalysts for alcohols under environmentally benign conditions . Hence, these catalysts can be used even in large-scale industrial syntheses .…”