康 · 学术 | Reaction of the Day No. 1773

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

Andrew G. Feng, Supeng Wu, Eric Palomo, and Robert R. Knowles*

Department of Chemistry, Princeton University, Princeton, New Jersey 08544, United States

—J. Am. Chem. Soc., 2026, doi: 10.1021/jacs.6c16630

Recommended by Zijing Chen_PDM

KEY WORDS: Carbonyl deoxygenation, Carbonyl reduction, photo chemistry, Wolff-Kishner reduction (反应类型); C(sp2)-H (成键类型); Ketones, aldehydes, Hydrazones (原料); Alkanes(产物)

ABSTRACT: The Wolff-Kishner reduction is a classical method for the deoxygenation of ketones and aldehydes, yet super stoichiometric 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 nearambienttemperature under essentially neutral conditions. By harnessing light energy to overcome thermodynamic constraints, this method addresses central drawbacks of traditional Wolff Kishnerreactivity, 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.

Background and this work

Substrate Scope of Aliphatic Carbonyls

Substrate Scope of Aryl Hydrazones

Plausible mechanism for aliphatic hydrazone reduction

Plausible mechanism for aryl hydrazone reduction

Summary and Comments

In summary, Robert R. Knowles et al. have developed a light-driven protocol for the Wolff-Kishner reduction of aryl and aliphatic carbonyls proceeding under essentially neutral conditions and near ambient temperature. Under these conditions, base-labile functional groups such as esters, amides, and α-carbonyl stereocenters are well tolerated. The significantly improved functional group compatibility of this method enables the application of the Wolff-Kishner reduction to more functionalized substrates than can be accommodated protocols. Preliminary mechanistic investigations distinct reactivities for aryl and aliphatic provided insights into how the thermodynamic constraints of classic ground-state transformations can be circumvented using visible-light photocatalysis. These insights into activation and reactivity may be applicable to other classical reactions mediated by strong base, such as the Bamford Stevens and Shapiro reactions, or potentially toward the design of new C?C bond-forming reactions.