Intramolecular Cyclopropanation of Active Methylene Derivatives Based on FeCl2 or FeCl3-Promoted Radical-Polar Crossover Reactions

Eito Yoshioka; Yuuki Imoto; Yousuke Yamaoka; Tomoko Ikeda; Hiroki Takahashi; Ryousuke Tanaka; Naoki Hayashi; Hideto Miyabe

doi:10.1002/chem.202400602

Intramolecular Cyclopropanation of Active Methylene Derivatives Based on FeCl2 or FeCl3-Promoted Radical-Polar Crossover Reactions

Chemistry. 2024 Apr 24:e202400602. doi: 10.1002/chem.202400602. Online ahead of print.

Authors

Eito Yoshioka¹, Yuuki Imoto¹, Yousuke Yamaoka¹, Tomoko Ikeda¹, Hiroki Takahashi¹, Ryousuke Tanaka¹, Naoki Hayashi¹, Hideto Miyabe²

Affiliations

¹ Hyogo Medical University, School of Pharmacy and Department of Pharmacy, JAPAN.
² Hyogo Medical University: Hyogo Ika Daigaku, School of Pharmacy and Department of Pharmacy, Minatojima 1-3-6, Chuo-ku, 650-8530, Kobe, JAPAN.

PMID: 38658317
DOI: 10.1002/chem.202400602

Abstract

Radical-polar crossover reactions were studied for the intramolecular cyclopropanation of active methylene derivatives. In the presence of FeCl3 as a stoichiometric oxidant and K2HPO4 as a base, the dehydrogenative cyclopropanation of active methylenes proceeded through the FeCl3-promoted oxidative radical cyclization followed by the ionic cyclization to give the bicyclic cyclopropanes. The use of α-chloro-active methylenes leads the subcatalytic cyclopropanation involving two redox pathways. In the presence of K2HPO4, the redox cyclopropanation proceeded by using FeCl2 (20 mol%) in combination with ligand (20 mol%).

Keywords: cyclopropanation; iron chloride; oxidative; radical; redox.