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Please login to access the full content or check if you have access via Enantioselective α-Fluorination of Arylacetic Acid Chlorides

DOI: 10.1055/sos-SD-134-00059

Champagne, P. A.; Drouin, M.; Paquin, J.-F.Science of Synthesis Knowledge Updates, (20161419.

While working on enantioselective chlorination and bromination of acid chlorides, Lectka wanted to extend this method to the analogous fluorination of acid chlorides (Scheme 1).[‌2‌] The dual activation strategy used a chiral nucleophile, benzoylquinidine (BQd, 2), and a transition-metal catalyst, such as palladium- or nickel-based phosphine complexes. Starting from acid chlorides, a ketene enolate coordinated to the metal is formed. Thus, electrophilic fluorine from N-fluorobenzenesulfonimide [NFSI; (PhSO2)2NF] is added in an enantioselective manner. The use of different nucleophiles to quench the reaction allows the formation of a broad range of products 3, such as carboxylic acids, amides, esters, and even peptide derivatives (total of 12 examples).

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Me8 Meeeeeee Me ee (%) Meeee (%) Mee
8-MeMM8M8 MeMe8(eeee) MMe 88 88 [‌8‌]
8-MeMM8M8 eeeee-MeMe8(MMe8)8 MMe 88 88 [‌8‌]
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