Reactions of epoxides involve attack by a nucleophile and proceed with ring-opening. For ethylene oxide: Nu—H + Nu—CH 2 CH 2 O—H H2CH2CH2CH2C CH 2 O In general...

For epoxides where the two carbons of the ring are differently substituted: In general... CH 2 O CRH Nucleophiles attack here when the reaction is catalyzed by acids: Anionic nucleophiles attack here:

Nucleophilic Ring-Opening Reactions of Epoxides

NaOCH 2 CH 3 CH 3 CH 2 OH (50%) Example O H2CH2CH2CH2C CH 2 CH 3 CH 2 O CH 2 CH 2 OH

O H2CH2CH2CH2C CH 2 CH 3 CH 2 O –Mechanism

O H2CH2CH2CH2C CH 2 CH 3 CH 2 O –– CH 3 CH 2 O CH 2 CH 2 O Mechanism

O H2CH2CH2CH2C CH 2 CH 3 CH 2 O –– CH 3 CH 2 O CH 2 CH 2 O O CH 2 CH 3 –H Mechanism

O H2CH2CH2CH2C CH 2 CH 3 CH 2 O –– CH 3 CH 2 O CH 2 CH 2 O CH 3 CH 2 O CH 2 CH 2 O H O CH 2 CH 3 – O CH 2 CH 3 –H Mechanism

(99%) Example O H2CH2CH2CH2C CH 2 KSCH 2 CH 2 CH 2 CH 3 ethanol-water, 0°C CH 2 CH 2 OH CH 3 CH 2 CH 2 CH 2 S

Stereochemistry Inversion of configuration at carbon being attacked by nucleophile Suggests S N 2-like transition state NaOCH 2 CH 3 CH 3 CH 2 OH O HHH OHOHOHOH H OCH 2 CH 3 (67%)

NH 3 H2OH2OH2OH2O (70%) R S R R Stereochemistry H3CH3CH3CH3C CH 3 H3CH3CH3CH3C O H H H H OH H2NH2NH2NH2N Inversion of configuration at carbon being attacked by nucleophile Suggests S N 2-like transition state

NH 3 H2OH2OH2OH2O (70%) ++++ ---- R S R R Stereochemistry H3CH3CH3CH3C CH 3 H3CH3CH3CH3C O H H H H OH H2NH2NH2NH2N H3NH3NH3NH3N O H3CH3CH3CH3C H H3CH3CH3CH3C H

NaOCH 3 CH 3 OH CH 3 CH CCH 3 CH 3 OHOHOHOH CH 3 O (53%) C C H H3CH3CH3CH3C CH 3 O consistent with S N 2-like transition state Anionic nucleophile attacks less-crowded carbon

(90%) Hydride attacks less-crowded carbon Lithium aluminum hydride reduces epoxides O H2CH2CH2CH2C CH(CH 2 ) 7 CH 3 1. LiAlH 4, diethyl ether 2. H 2 O OHOHOHOH H3CH3CH3CH3C CH(CH 2 ) 7 CH 3

Acid-Catalyzed Ring-Opening Reactions of Epoxides

Example O H2CH2CH2CH2C CH 2 CH 3 CH 2 OCH 2 CH 2 OH (87-92%) CH 3 CH 2 OCH 2 CH 2 OCH 2 CH 3 formed only on heating and/or longer reaction times CH 3 CH 2 OH H 2 SO 4, 25°C

Example O H2CH2CH2CH2C CH 2 HBr 10°C BrCH 2 CH 2 OH (87-92%) BrCH 2 CH 2 Br formed only on heating and/or longer reaction times

Mechanism O H2CH2CH2CH2C CH 2 + H Br – O H2CH2CH2CH2C CH 2 + H Br

Mechanism O H2CH2CH2CH2C CH 2 + H O Br CH 2 CH 2 H Br – O H2CH2CH2CH2C CH 2 + H Br

Acid-Catalyzed Hydrolysis of Ethylene Oxide O H2CH2CH2CH2C CH 2 + H O H2CH2CH2CH2C CH 2 + O HHH + O H H Step 1

Acid-Catalyzed Hydrolysis of Ethylene Oxide O H2CH2CH2CH2C CH 2 O +HH H Step 2 + O O CH 2 CH 2 HH H

Acid-Catalyzed Hydrolysis of Ethylene Oxide O HH Step 3 + O O CH 2 CH 2 HH H O HH + H O O CH 2 CH 2 HH

Acid-Catalyzed Ring Opening of Epoxides nucleophile attacks more substituted carbon of protonated epoxide inversion of configuration at site of nucleophilic attack Characteristics:

CH 3 OH CH 3 CH CCH 3 CH 3 OHOHOHOH OCH 3 (76%) C C H H3CH3CH3CH3C CH 3 O consistent with carbocation character at transition state Nucleophile attacks more-substituted carbon H 2 SO 4

Stereochemistry Inversion of configuration at carbon being attacked by nucleophile (73%) HHO HBr H OHOHOHOH Br H

(57%) R S R R Stereochemistry H3CH3CH3CH3C CH 3 H3CH3CH3CH3C O H H H H OH CH 3 O Inversion of configuration at carbon being attacked by nucleophile CH 3 OH H 2 SO 4

R S R R Stereochemistry H3CH3CH3CH3C CH 3 H3CH3CH3CH3C O H H H H OH CH 3 O CH 3 OH H 2 SO 4 ++++ ++++ CH 3 O O H3CH3CH3CH3C H H3CH3CH3CH3C H H ++++ H