Grob fragmentation

A Grob fragmentation, named for the British chemist Cyril A. Grob, is an elimination reaction taking place when an electrofuge and nucleofuge are situated in positions 1 and 3 on an aliphatic chain. The reaction product is an electrofugal fragment (carbonium ion, acylium ion), an unsaturated fragment (alkene, alkyne, imine) and a nucleofugal fragment (leaving group such as tosyl, hydroxyl).



The reaction mechanism varies with reactant and reaction conditions with the fragmentation taking place in a concerted reaction, taking place in two steps with a carbocationic intermediate when the nucleofuge leaves first or taking place in two steps with an anionic intermediate when the electrofuge leaves first.

An example of a Grob-like fragmentation in organic synthesis is the expansion of the Wieland-Miescher ketone (1 in scheme 1) to Thapsigargin.



Another example is an epoxy alcohol fragmentation reaction as part of the Holton Taxol total synthesis.