Chapter 16: Ethers, Epoxides and Sulfides

S_N2 type Reactions of Epoxides

• Reactive nucleophiles react with epoxides in an S_N2 type of reaction.
• Reactive nucleophiles are usually anions so the reaction conditions are essentially basic.
• Examples of such nucleophilic systems are :  RMgX, RLi, RC≡CM, LiAlH₄, HO^-, RO^-
• The leaving group is the oxygen atom of the epoxide in the form of the alkoxide which is converted to the alcohol on an acidic work-up.
• For non-symmetrical epoxides, there is a question of regioselectivity:

Scenario 1: The Nu attacks the more substituted C of the epoxide at 180o to the C-O bond that breaks.
Scenario 2: The Nu attacks the least hindered end of the epoxide at 180o to the C-O bond that breaks.

• Experimental results show that scenario 2 is observed by these stronger nucleophiles such as Grignard reagents, RMgBr.
• Recall that S_N2 reactions of alkyl halides follow the order CH₃-  >  1^o  >  2^o  (i.e. favours the less substituted system)
• Reactive nucleophiles attack the least hindered end of the epoxide in an S_N2 type fashion at 180^o to the leaving group bond.
• This results in the formation of the more substituted alcohol.
• What about stereochemistry ? Since the nucleophile attacks on the opposite side as the epoxide O leaves, there is an inversion at that center.

• Under basic conditions, epoxides open in an "S_N2 like" fashion with the nucleophile attacking the less substituted end and with inversion of stereochemistry at that center.

© Dr. Ian Hunt, Department of Chemistry