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Updated: Aug 11, 2026

A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species
Published on: August 16, 2018
Reactive ketimino radical acceptors: intermolecular alkyl radical addition to imines with a phenolic hydroxyl group
Hideto Miyabe1, Yousuke Yamaoka, Yoshiji Takemoto
1Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.
Abstract:
Intermolecular carbon radical addition to the carbon-nitrogen double bond of ketimines was studied. In the study on the reactivity of various aldimines, we found that the aldimine 7 having a phenolic hydroxyl group shows an excellent reactivity toward nucleophilic carbon radicals. A remarkable effect of phenolic hydroxyl group is assumed to be the stabilization of intermediate aminyl radical provided by a hydroxyl group. The screening of reactive ketimino acceptors showed that ketimines 15, 17, and 19 having a phenolic hydroxyl group exhibit excellent reactivities. The radical addition to ketimines 15, 17, and 19 took place regioselectively at the imino carbon to give the C-alkylated products without the formation of N-alkylated products. Enantioselective ethyl radical addition to ketimine 15 using chiral box ligand and Zn(OTf)2 gave the diethylated product 30 in 80% ee.
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