Chem 215 F07 Notes – Dr. Masato Koreeda - Page 1 of 4.

Date: September 21, 2007

Chapter 13. Alcohols, Diols, and Ethers: V. Reactions of alcohols: Alcohols to alkyl halides

VIII. Epoxides (or Oxiranes):

b. Ring-opening reactions of epoxides: Epoxides are highly strained and easily undergo
ring-opening reactions under both acidic and basic conditions.
Acidic conditions: ring-opening reactions proceed rapidly at low temperatures (usually at room temp or
below); elongated C-O bonds of the protonated, highly strained epoxides believed to be the origin of high
reactivity.
Acyclic epoxides
H Br
O H OH HO CH3
HBr H3C
H H H + H H
0 °C
H3C CH3 Br CH3 H3C Br
meso (2S,3S) (2R,3R)
racemic mixture

H H
SN2-like O O SN2-like
inversion of H inversion of
H H H
stereochemistry H3C CH3 H3C CH3 stereochemistry
here! here!
Br Br

Cyclic-fused epoxides
O H O H trans-
H product
O O H
CH3OH
O O CH3
H CH3
O
H CH3 + enantiomer
O
inversion of H CH3
stereochemistry or simply B

Note: The mechanism for the ring-opening of epxodies under acidic conditions is quite similar to that of
bromination of alkenes.
bromonium Br
Br Br Br ion trans-
intermediate product
Br
inversion of
Br stereochemistry + enantiomer

Stereochemical/regiochemical issues:
O H3C OH regiochemically, stereochemically
H3O18 D3C clean formation of this diol.
H3C H H
0 °C
D3C CH3 CH3
HO18
retention
stereochemical
inversion Specific incorporation of HO18 here!
observed here!
Chem 215 F07 Notes – Dr. Masato Koreeda - Page 2 of 4. Date: September 21, 2007

Mechanistic interpretation on the stereochemical/regiochemical outcome under acidic

conditions:
more elongated C--OH bond;
-charge delocalized because
this more substituted C can
H better stalilize the postive charge
O18 H
H H H
O O O

H3C H H3C H H3C H

D3C CH3 D3C CH3 D3C CH3

Can accommodate
In the transition state for the attack of H2O (H2O18 in this case), H
charge better here!
the nucleophile attacks preferentially the carbon center that can O
better stabilize a positive character (i.e., the more substituted H3C
carbon). H
D3C
CH3
H2O18
H3C OH
D3C an SN2-like stereochemical
H
inverstion at a more substituted
CH3
HO18 carbon center
retention
stereochemical
inversion Specific incorporation of HO18 here!
observed here!

Epoxide-ring opening under basic conditions

A straight SN2 process at the less-substituted carbon with a stereochemical inversion.

Na H OCH2CH3
O O
H3CCH2O Na H
H O H
H3C H3CCH2OH H3C D
D
H3C D H3C H3C
H3CCH2O H3C OCH2CH3

less-substituted C; Na
SN2 reaction here! HO H
D
OCH2CH3 + H3C
Na H3C OCH2CH3

Summary of epoxide-ring opening reactions:

Acidic conditions: SN2 like interm of the stereochemical inversion, but at the more
substituted C.
Ring opening at the more substituted C with the inversion of stereochemistry.
Basic conditions: pure SN2
Ring opening at the less substituted C with the inversion of stereochemistry.
Chem 215 F07 Notes – Dr. Masato Koreeda - Page 3 of 4. Date: September 21, 2007

1,2-Diaxial opening of cyclohexene oxide

H3O OH
O OH
OH HO more stable conformer

H
H O OH
O
axial-like axial

axial-like axial
OH
H2O
thermodynamically
only 1,2-diaxial transition state feasible less favored conformer
for an SN2 like process to occur
This is the form produced first, then
inverts to the top conformer.

Problems: Show the structure of the expected major product for each of the following two
epoxide ring-opening reactions.

CH3OH, H+

H3CO Na
CH3OH