Reaction of epoxides with nucleophiles under basic conditions
Description: When epoxides are treated with negatively charged nucleophiles, they will add to the least substituted position of the epoxide in an SN2 reaction.
Notes: Recall that epoxides are unlike normal ethers in that they have considerable ring strain due to the 3 membered ring.
- The purpose of the acid in the second step is to protonate the negatively charged oxygen that is formed when the epoxide is opened. This results in formation of a neutral alcohol.
- Where addition occurs to a stereocenter, the stereochemistry of the carbon will invert.
- Some examples of nucleophiles that will add to epoxides include hydroxyl (HO-) alkoxy (RO-), Grignard reagents and (sometimes) organocuprates (Gilman reagents)
Notes: This depicts opening of an epoxide by a Grignard reagent. The second step is protonation of the oxygen with H3O(+).
Note that there is nothing special about Cl(-) here, it’s just a spectator ion with H3O(+)
(Advanced) References and Further Reading
- Base-Promoted Isomerizations of Epoxides
Crandall, Jack K.; Apparu, Marcel
React. 1983, 29, 345-443
- Selective transformations of 2,3-epoxy alcohols and related derivatives. Strategies for nucleophilic attack at carbon-3 or carbon-2
Carl H. Behrens and K. Barry Sharpless
The Journal of Organic Chemistry 1985, 50 (26), 5696-5704
- Stereochemistry of the base-induced rearrangement of epoxides to allylic alcohols
Randolph P. Thummel and Bruce Rickborn
Journal of the American Chemical Society 1970, 92 (7), 2064-2067
- Organoaluminum reagents of type R1R2NAlEt2 which allow regiospecific isomerization of epoxides to allylic alcohols
Arata Yasuda, Shin Tanaka, Koichiro Oshima, Hisashi Yamamoto, and Hitosi Nozaki
Journal of the American Chemical Society 1974, 96 (20), 6513-6514
- Controlled chemical synthesis of the enzymically produced eicosanoids 11-, 12-, and 15-HETE from arachidonic acid and conversion into the corresponding hydroperoxides (HPETE)
E. J. Corey, Anthony Marfat, J. R. Falck, and John O. Albright
Journal of the American Chemical Society 1980, 102 (4), 1433-1435
- CYCLOHEXENE IMINE (7-AZA-BICYCLO[4.1.0]HEPTANE)
Iain D. G. Watson, Nicholas Afagh and Andrei K. Yudin
Org. Synth. 2010, 87, 161-169
This is a particularly useful procedure, as it is a Staudinger reaction for converting epoxides to NH-aziridines (the nitrogen analog of epoxides). The synthesis can be tricky, but a lot of detail has been provided here so that this can be reproduced, as fitting a procedure in Organic Syntheses.