Opening of epoxides with nucleophiles under acidic conditions

by James

Description: When acid is added to epoxides, nucleophiles will add to the more substituted position. The stereochemistry of the addition is trans.
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Notes: Some examples of nucleophiles that will add to epoxides are water, alcohols and halides. Remember that epoxides are unusually reactive due to their considerable ring strain.

Examples: Note that in the second example the stereochemistry is trans and the nucleophile (water) has attacked the more substituted position of the epoxide. In the third example, methanol is the solvent. Note the fourth example is an intramolecular reaction (often gives students trouble!)

Notes: Note that the addition is Markovnikoff in each case (nucleophile adding to the most substituted carbon). In the last example, this is an example of an intramolecular reaction.

Mechanism: Protonation of the epoxide (Step 1, arrows A and B) make the carbons adjacent to the oxygen much more susceptible to nucleophilic attack (more electrophilic). The nucleophile will preferentially attack the carbon best able to support positive charge – that is, the most substituted carbon. Attack on this carbon from the backside (Step 2, arrows C and D) lead to a trans product, which is then deprotonated (Step 3, arrows E and F).

Notes: There’s nothing special about HSO4(-) here. Addition of sulfuric acid to water gives H3O(+) HSO4(-) which is often abbreviated H3O(+). My personal preference is to show the counter-ion.

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{ 3 comments… read them below or add one }

sam

So helpful thank you!!!!

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Jeremy McMurray

Sir does the methyl substituent have any stereochemistry at the end?

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james

yes, it is “up” in the example shown in the mechanism. The fact that OH is drawn as a “dash” implies that the methyl group is a “wedge” (up) although I was lazy and did not draw it in as such.
The reaction proceeds with inversion of configuration.

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