Grob Fragmentation

Abstract

The cleavage of an amine of a suitable β‐leaving group in the presence of a base, where the leaving group is a halogen or tosyl group, is generally referred to as the Grob fragmentation. This reaction occurs via either a concerted or stepwise mechanism, depending on the stereochemical and stereoelectronic factors. A two‐step concerted mechanism with zero activation energy for the second step has also been reported. Under basic conditions, this reaction has been challenged by nucleophilic substitution, elimination, and cyclization; therefore, some modifications have been developed to carry out such fragmentation under milder conditions. The intramolecular version of this reaction has been extensively applied to the synthesis of compounds with medium‐size rings. When central carbon atom is replaced by a nitrogen atom, the comparable cleavage is known as aza ‐Grob fragmentation.