Abstract
Site-selective nucleophilic ring-opening reactions of 2-arylazetidine-2-carboxylic acid ester-derived tetraalkyl ammonium salts 2 with tetrabutylammonium halides (Bu4NX) to give tertiary alkyl halides are successfully demonstrated. For example, a nucleophilic ring-opening reaction of 2-(o-tolyl) derivative 2a with 1.2 equivalents of tetrabutylammonium fluoride (Bu4NF) in THF at 60 °C preferentially proceeded at a more substituted carbon atom (2-position) compared to a less-substituted carbon atom (4-position) and afforded tert-butyl 4-(dimethylamino)-2-fluoro-2-(o-tolyl)butanoate 3aa in 71% yield as the corresponding tertiary alkyl fluoride. This result was applied to synthesize optically active organofluorine compounds starting from commercially available (R)-1-phenylethylamine.
Highlights
Ring-strained four-membered N-heterocycle azetidines are valuable building blocks in organic synthesis
We attempted a reaction with a THF solution of Bu4NF, and the desired 3aa was obtained in 33% yield with trace amounts of 4aa (
We described that the site-selective nucleophilic ring-opening reaction of 2-arylazetidine-2-carboxylic acid esterderived ammonium salts 2 with Bu4NF or Bu4NCl proceeded at a much-substituted 2-position preferentially over a lesssubstituted 4-position and produced the corresponding tertiary alkyl uorides and chlorides 3
Summary
Ring-strained four-membered N-heterocycle azetidines are valuable building blocks in organic synthesis. We attempted the reactions of 5-substituted aryl derivatives 2a–e with Bu4NF and obtained the corresponding organo uorine compounds 3ba–ea in moderate yields (entries 1–4).
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