Tetrahedral intermediates in reactions of carboxylic acid derivatives with nucleophiles

Transacylation reactions of carboxylic acids, carboxylic acid esters, carboxylic acid amides and other carboxylic acid derivatives are among the most widespread and most important reactions in chemistry and biochemistry. Already in 1887, Claisen suggested a tetrahedral intermediate in transformations of carboxylic acid derivatives with nucleophiles. A historical overview gives insight into the studies to detect possible tetrahedral intermediates in such reactions. However, only in recent years has detailed information concerning the structures of such species become available. In this review, neutral, cationic and anionic tetrahedral intermediates are described which serve as models for transacylations under neutral, acid-catalysed or basic conditions. The characteristically different structures correspond nicely with experimental experience with reactions of carboxylic acid derivatives and with quantum chemical model calculations on tetrahedral intermediates. Finally, by means of model calculations, an explanation is given for the fast reactions of Weinreb amides, RC(O)N(CH3)OCH3, with organolithium and even with Grignard reagents: the reactions are determined by comparatively stable chelate transition states. Copyright (C) 2004 John Wiley Sons, Ltd.