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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: Note that the nucleophiles add to the less substituted position of the epoxide.Base is catalytic in the bottom three reactions. Note that the fourth example is a tricky example of an intramolecularreaction. NaOH deprotonates the alcohol, which then attacks the epoxide.
Mechanism: Attack of the nucleophile on the least substituted carbon of the epoxide (SN2 reaction) (Step 1, arrows A and B) results in opening of the strained epoxide. This is followed by protonation of the resulting negatively charged oxygen (“alkoxide”) with acid (Step 2, arrows C and D) to give the neutral alcohol.

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(+)