Grob fragmentation
A Grob fragmentation is an elimination reaction taking place when an electrofuge and nucleofuge are situated in positions 1 and 3 on an aliphatic chain [1]. 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 was first published about by C.A. Grob in 1955.
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 [2] [3]
Another example is an epoxy alcohol fragmentation reaction as part of the Holton Taxol total synthes
References
- ^ Strategic Applications of Named Reactions in Organic Synthesis Laszlo Kurti, Barbara Czako Academic Press (March 4, 2005) ISBN 0124297854
- ^ Synthesis of the thapsigargins Steven V. Ley et. al PNAS | August 17, 2004 | vol. 101 | no. 33 | Abstract and online article
- ^ Reaction details: organic reduction of Wieland-Miescher ketone with sodium borohydride to alcohol 2 followed by functionalizion to mesylate 3 with mesyl chloride in pyridine. Then reduction of enone to allyl alcohol 4 with tri-tert-butoxyaluminum hydride in tetrahydrofuran followed by hydroboration with borane in THF to borane 5 (only one substituent displayed for clarity). The Grob fragmentation to 6 takes place with sodium methoxide in methanol at reflux