Reimagining the Wolff-Kishner Reduction: Light-Driven Carbonyl Deoxygenation without Strong Base

Abstract

The Wolff-Kishner reduction is a classical method for the deoxygenation of ketones and aldehydes, yet superstoichiometric amounts of strong base and high temperatures are generally required. Herein, we report a light-driven protocol for the Wolff-Kishner reduction of aryl and aliphatic carbonyls at near-ambient temperature under essentially neutral conditions. By harnessing light energy to overcome thermodynamic constraints, this method addresses central drawbacks of traditional Wolff-Kishner reactivity, such as ester and amide hydrolysis, α-carbonyl epimerization, and azine formation. Preliminary mechanistic studies provide insights into the distinct, substrate-dependent activation modes and reaction pathways. This work further illustrates the ways in which excited-state reactivity paradigms can enable the reimagination of classical organic transformations.