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).

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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