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Updated: Aug 18, 2025

A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species
Published on: August 16, 2018
LiHMDS-Mediated Deprotonative Coupling of Toluenes with Ketones
Masanori Shigeno1,2, Akihisa Kajima1, Eito Toyama1
1Department of Biophysical Chemistry Graduate School of Pharmaceutical Science, Tohoku University, 6-3 Aoba, Sendai, 980-8578, Japan.
Abstract:
We demonstrate that lithium hexamethyldisilazide (LiHMDS) acts as an effective base for deprotonative coupling reactions of toluenes with ketones to afford stilbenes. Various functionalities (halogen, OCF3 , amide, Me, aryl, alkenyl, alkynyl, SMe, and SPh) are allowed on the toluenes. Notably, this system proved successful with low-reactive toluenes bearing a large pKa value compared to that of the conjugate acid of LiHMDS (hexamethyldisilazane, 25.8, THF), as demonstrated by 4-phenyltoluene (38.57, THF) and toluene itself (∼43, DMSO).
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