Formamides as Lewis Base Catalysts in S N Reactions—Efficient Transformation of Alcohols into Chlorides, Amines, and Ethers

A simple formamide catalyst facilitates the efficient transformation of alcohols into alkyl chlorides with benzoyl chloride as the sole reagent. These nucleophilic substitutions proceed through iminium‐activated alcohols as intermediates. The novel method, which can be even performed under solvent‐f...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2016-08, Vol.55 (34), p.10145-10149
Main Authors: Huy, Peter H., Motsch, Sebastian, Kappler, Sarah M.
Format: Article
Language:English
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Summary:A simple formamide catalyst facilitates the efficient transformation of alcohols into alkyl chlorides with benzoyl chloride as the sole reagent. These nucleophilic substitutions proceed through iminium‐activated alcohols as intermediates. The novel method, which can be even performed under solvent‐free conditions, is distinguished by an excellent functional group tolerance, scalability (>100 g) and waste‐balance (E‐factor down to 2). Chiral substrates are converted with excellent levels of stereochemical inversion (99 %→≥95 % ee ). In a practical one‐pot procedure, the primary formed chlorides can be further transformed into amines, azides, ethers, sulfides, and nitriles. The value of the method was demonstrated in straightforward syntheses of the drugs rac ‐Clopidogrel and S ‐Fendiline.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201604921