Epoxides – Basic and Acidic

Epoxides are cyclic ethers with a lot of ring strain (since they’re 3 membered rings – interior angle of 60 degrees instead of the ideal 109 degrees). So opening of epoxides is a very favorable reaction. Ring-opening reactions of epoxides can be a little bit confusing to some students because the patterns change depending on conditions.  Thankfully, once you see the pattern, identifying which pattern to apply is fairly straightforward. What’s better, these are patterns you’ve already learned in Org 1. 

There are two ways to open epoxides:  under acidic conditions or under basic conditions. And the conditions used will affect the products that you get.

• Under acidic conditions [e.g. if you see H3O(+) or H(+) ] , you protonate the epoxide oxygen. This makes it into an “oxonium ion”, which is now similar in reactivity to a bromonium ion. Back in Org 1 you could have seen examples where nucleophiles add to the more substituted carbon of a bromonium ion because that’s the carbon which stabilizes positive charge the best. In that sense it resembles “Markovnikoff selectivity” – adding to the most substituted carbon, except here it’s the more substituted carbon of theepoxide intstead of that of the double bond.
• Under basic conditions (e.g. HO–, CH3O–, RMgX, etc.)  you can think of opening an epoxide as being like an SN2 reaction. The big barrier to the SN2 is steric hindrance, so the nucleophile will go after the less substitutedcarbon of the epoxide.

Last thing: if the nucleophilic attack occurs on a stereocenter, don’t forget that you’re going to have inversion of stereochemistry at that carbon.

Tomorrow: The single best contribution of France to organic chemistry – the Grignard reaction.
Thanks for reading! James