KetoABNO/NO_x Cocatalytic Aerobic Oxidation of Aldehydes to Carboxylic Acids and Access to α-Chiral Carboxylic Acids via Sequential Asymmetric Hydroformylation/Oxidation

Abstract

A method for aerobic oxidation of aldehydes to carboxylic acids has been developed using organic nitroxyl and NOx co-catalysts. KetoABNO (9-azabicyclo[3.3.1]nonan-3-one N-oxyl) and NaNO2 were identified as the optimal nitroxyl and NOx sources, respectively. The mildness of the reaction conditions enable sequential asymmetric hydroformylation of alkenes/aerobic aldehyde oxidation to access α-chiral carboxylic acids without racemization. The scope, utility, and limitations of the oxidation method are further evaluated with a series of achiral aldehydes bearing diverse functional groups.

Chemoselective Conversion from α-Hydroxy Acids to α-Keto Acids Enabled by Nitroxyl-Radical-Catalyzed Aerobic Oxidation

“…The reaction completed in MeCN to provide α-keto acid 1b in high yield, without the recovery of 1a (entry 13). Keto-ABNO- and ABNO-catalyzed aerobic oxidation afforded moderate yields of 1b together with the recovery of 1a (entries 14 and 15) …”

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

“…Among the various conditions for nitroxyl radical-catalyzed alcohol oxidation, we chose aerobic oxidation conditions using nitroxyl radical catalysts because molecular oxygen is an abundant and environmentally benign oxidant. Because the nitroxyl radical itself does not promote aerobic alcohol oxidation efficiently, a NO x source and copper salt , were used as cocatalysts to efficiently promote aerobic alcohol oxidation. Both nitroxyl radical/NO x and nitroxyl radical/copper catalytic systems efficiently oxidized alcohols at ambient temperatures under ambient air pressures; however, their active species differed.…”

Condensation Oligomers with Sequence Control but without Coupling Reagents and Protecting Groups via Asymmetric Hydroformylation and Hydroacyloxylation

“…Oxidation of the aldehydes afforded the corresponding carboxylic acids 3 , 6 , 9 , and 12 in 70 to 95% yield under Pinnick oxidation conditions without epimerization. Although Pinnick oxidation uses stoichiometric reagents, emerging catalytic aldehyde oxidation methods have the potential to improve the efficiency of this step …”