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Formamides as Lewis Base Catalysts in S N Reactions—Efficient Transformation of Alcohols into Chlorides, Amines, and Ethers
Author(s) -
Huy Peter H.,
Motsch Sebastian,
Kappler Sarah M.
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201604921
Subject(s) - formamides , chemistry , formamide , catalysis , reagent , organic chemistry , iminium , acetonitrile , nucleophile , lewis acids and bases , alkyl , combinatorial chemistry
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.