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Updated: Jun 27, 2026

A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species
Published on: August 16, 2018
Catalytic, asymmetric alpha-fluorination of acid chlorides: dual metal-ketene enolate activation
Daniel H Paull1, Michael T Scerba, Ethan Alden-Danforth
1Johns Hopkins University, Department of Chemistry, 3400 North Charles Street, Baltimore, Maryland 21218, USA.
Abstract:
In this Communication, we disclose a catalytic, highly enantioselective (up to >99% ee) alpha-fluorination of acid chlorides to produce a variety of optically active carboxylic acid derivatives from readily accessible and commercially available starting materials. The reaction depends on dually activated ketene enolates generated from two discrete catalysts--a chiral nucleophile and an achiral transition metal complex working in tandem. The active, putative alpha-fluorobis(sulfonimide) intermediates readily transacylate in situ under mild conditions upon addition of a wide variety of nucleophiles, including complex natural products. As a consequence, the power of this method is witnessed by the broad range of alpha-fluorinated products that can be accessed efficiently depending on the work up conditions.
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