If the epoxide is protonated first, the acid will destroy the Grignard. It’s possible to accelerate Grignard-type additions to epoxides with Lewis acids (e.g. BF3) that are compatible with strong bases.

But what if the epoxide is protonated first (activated), and Grignard reagent is added later, would it still add at the less substituted carbon, or would addition take place at the more substituted carbon, like that of epoxide opening in acidic medium.

OK, so what’s the strongest base? The epoxide oxygen. So protonate the oxygen, forming a new O-H bond and breaking the H-Cl bond. Now you have a protonated epoxide with a Cl- floating around. Cl- can be a good nucleophile. So what happens next?

Thank you, Bo, for taking the time to write out a long explanation to help a reader.

You’d start with the appropriately substituted alkene and then do an epoxidation reaction. For acrylonitrile you’d need a nucleophilic epoxidizing reagent like H2O2/NaOH.

The acetylide ion is a basic nucleophile and will attack the least substituted carbon in SN2 fashion. The water is added after the reaction is over to quench the alkoxide anion.

Generally not. LiBH4 can do it.

Amines are at least 10 orders of magnitude more basic than epoxides, so any acid added to the system will protonate the amine, not the epoxide. Protonating the amine makes it into an ammonium salt, which is non-nucleophilic. That’s why the reaction slows down. Acid slows down the rate of addition of Grignards to epoxides too.

No, they wouldn’t be carbocation rearrangements, in acidic opening of epoxides, because there likely won’t be a free carbocation.

However, there are pinacol-related rearrangements that can occur with epoxides when acid is added in the absence of nucleophiles, such as the epoxide-aldehyde rearrangement.