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Updated: Jan 4, 2026

A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species
Published on: August 16, 2018
Intermolecular Stereospecific Substitution of Underivatized Enantioenriched Secondary Alcohols by Organocatalysis
Sunisa Akkarasamiyo1, Joseph S M Samec2
1Laboratory of Medicinal Chemistry, Chulabhorn Research Institute, 54 Kamphaeng Phet 6 Road, Laksi, Bangkok, 10210, Thailand.
Abstract:
The stereospecific substitution of non-derivatized and non-allylic enantioenriched alcohols with only water as a by-product would enable the use of readily available alcohols as substrates for green and sustainable transformations. However, the poor leaving group ability of the OH group has hampered the development of such a process. Denton and co-workers recently described the use of (2-hydroxybenzyl)diphenylphosphine oxide as a catalyst of a redox-neutral and zero-waste-generating Mitsunobu reaction. This innovative process constitutes the first intermolecular stereospecific substitution of non-allylic alcohols, and might find industrial applications.
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Preparation of Alcohols via Substitution Reactions
Alcohols can be synthesized from alkyl halides via nucleophilic substitution reactions. The highly polar carbon-halogen bond in the substrate makes halide a good leaving group. The hydroxide ion or water can act as a nucleophile to take the place of halide and form an alcohol. The substitution reactions occur via two different reaction pathways, SN1 or SN2, depending on the nature of carbon attached to the halide.
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