Grob Fragmentation

An interesting and generally useful skeletal transformation, involving specific carbon-carbon bond cleavage with accompanying conversion of certain sigma-bonds to pi-bonds, is known as the Grob fragmentation. As background for discussing this reaction, it is helpful to define the concept of ethylogy, which may be regarded as the sigma-bond equivalent of vinylogy. This is illustrated in the following diagram. Here a simple nucleophilic fragmentation at M is converted to an ethylagous analog by the insertion of a two carbon (ethyl) segment between the reacting moieties.

A simple example of an ethylagous relationship may be found by comparing the acid or base-catalyzed loss of water from a carbonyl hydrate with the retro aldol cleavage reaction. This will be shown above by clicking on the diagram. The carbon atoms of the ethylagous unit are colored green.

Whenever functional group interactions occur through a chain of covalent bonds (sigma or pi), stereoelectronic factors will play an important role. This is demonstrated by the stereoisomeric amino chlorides in the following diagram. The non-ethylagous analog for the reaction is drawn in the gray-shaded box. A Grob fragmentation takes place in the top example, because the orbitals of the bonding and non-bonding electron pairs participating in the reaction are aligned properly. These are the non-bonding pair on nitrogen and the bonding pairs in the green-colored covalent bonds. Their alignment is a function of their relative orientation on the brown-colored bonds. As drawn, the reacting electron pairs on each such bond are anti, the preferred configuration for maximum overlap. In the bottom epimer the chlorine atom is not oriented properly, and a slower bimolecular E2 elimination is observed.

Other examples of Grob fragmentations will be shown above . The first is a useful ring enlargement reaction in which the common bond of a fused bicyclic skeleton is cleaved, yielding a larger carbocycle.