Does anyone know if it is possible to open an epoxide and do a 2-C extension using an enolate ion, say, of acetone? Here's an example of what I mean:

enter image description here

Based on what I know of enolate chemistry, this shouldn't be problematic, but I've never seen it.

I have done some preliminary literature searching and checked out masterorganicchemistry.com, etc. but have not been able to find anything about this.


Never say never! :-) Here is the answer for your question (Ref.1):

Abstract: We report here that (1) enolate anions of five- to seven-membered cycloalkanones nucleophilically open cyclopentene and cyclohexene oxides in 57−76% yields and with 4−8:1 diastereoselectivity; (2) enolate anions formed regiospecifically via kinetic deprotonation of 2-cyclohexenone and 2-cycloheptenone open cyclohexene oxide in 60−62% yields and with 32−95:1 diastereoselectivity; and (3) an aryl methyl ketone enolate anion opens a monosubstituted epoxide as the key step in a short synthesis of the $\gamma$-hydroxyketone (GHK) aglycon of the natural product curculigine.

Graphical Abstract:

Epoxide Opening by Enolates

The product(s) and selectivity are depicted in following scheme:

Epoxide Opening


  1. G. H. Posner, J. P. Maxwell†, M. Kahraman, "Mild, Fast, and Stereoselective Epoxide Opening by Ketone Enolate Anions. Application to Synthesis of the Norlignan Curculigine," J. Org. Chem. 2003, 68(8), 3049–3054 (DOI: 10.1021/jo020744q).
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    $\begingroup$ That's somewhat interesting that the O-alkylation decreases when the counterion is changed from Li -> Na -> K; I would have expected it the other way around (Li should associate tightly with the negatively charged oxygen). $\endgroup$ – orthocresol Apr 12 at 6:24

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