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Updated: May 29, 2025

A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species
Published on: August 16, 2018
Universal Reagent for Mild and Stereospecific Nucleophilic Substitution of Alcohols with Amines
William S Bechara1, Irina K Sagamanova1, Léa Thai-Savard1
1Université de Montréal, FRQNT Centre in Green Chemistry and Catalysis, Centre for Continuous Flow Synthesis, Department of Chemistry, 1375 av. Thérèse Lavoie-Roux, Montréal, QC, H2V 0B3, Canada.
Abstract:
A user-friendly reagent for mild and general activation of alcohols towards bimolecular nucleophilic substitution (SN2) leveraging diverse nucleophiles, including primary and secondary amines is reported herein. The new ion-paired reagent discovery was based upon the putative zwitterionic betaine intermediate of the Mitsunobu reaction and enabled the one-step conversion of enantioenriched alcohols to valuable chiral C-X bonds (where X=N, C, S, O or halide). The described activating reagent has also been applied to a one-step methylation reaction using methanol and to an intermolecular amination/intramolecular cyclization sequence that generates heterocycles, such as tetrahydroisoquinolines. This work provides the first evidence by X-ray crystallography of a protonated betaine as intermediate in the Mitsunobu reaction.
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