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.^[1][2][3] 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).

Additional recommended knowledge

Recognize and detect the effects of electrostatic charges on your balance

Daily Visual Balance Check

How to ensure accurate weighing results every day?

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.^[4][5]

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

References

1. ^ Grob, C. A.; Baumann, W. Helv. Chim. Acta 1955, 38, 594.
2. ^ Weyerstahl, P.; Marschall, H. Comp. Org. Syn. 1991, 6, 1044-1065. (Review)
3. ^ Strategic Applications of Named Reactions in Organic Synthesis Laszlo Kurti, Barbara Czako Academic Press (March 4, 2005) ISBN 0-12-429785-4
4. ^ Synthesis of the thapsigargins Steven V. Ley et. al PNAS | August 17, 2004 | vol. 101 | no. 33 | Abstract and online article
5. ^ 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. A methoxide group attacks boron giving the borate complex which fragments. As each boron atom can hold three substrate molecules (R), the ultimate boron byproduct is trimethyl borate

See also

• Eschenmoser fragmentation
• Wharton reaction