Analysis of the Stereoselectivity of Dihydroxylation Reactions
Question: Are dihydroxylation reactions stereoselective or not stereoselective? If the
reactions are stereoselective, which isomer is formed preferentially under each set of
conditions?
Background: Dihydroxylation is the process of adding two hydroxyl groups to an alkene
to form a diol. Because the same group is being added to both sides of the double bond,
the regiochemistry of dihydroxylation is unambiguous, but the stereochemistry of the
addition must be considered. There are two possible stereochemical outcomes for
dihydroylation: syn addition leads to the cis diol product; anti addition leads to a racemic
mix of the trans diol product. Two possible stereochemical outcomes for the
dihydroxylation of cylclohexene are shown in Figure 1.
Figure 1
OH
OH
+
?
OH
OH
?
OH
OH
In this lab period, you will perform two reactions that transform alkenes into diols. In the
first experiment, you will use an oxidizer that you may not have discussed in lecture
called Oxone ®. Oxone is a persulfate mix that reacts with acetone to produce
dimethyldioxirane. (Figure 2) Consider the dioxirane to have the same reactivity as
peroxyacids such as mCPBA or MMPP, which transform alkenes into epoxides. In the
second experiment, you will use a common oxidizing agent, KMnO4 under cold, basic
conditions.
Figure 2. Formation of cyclohexane-1,2-diol from cyclohexene
O
A.
O
HO S OH
O O
O O
oxone
dimethyldioxirane
B.
KMnO4, OH-, cold
H3O+
OH
O
OH
epoxide
OH
OH
diol
Procedure Part A: Oxone reaction: Dissolve 0.40 g Oxone ® in 2.0 mL of water by
shaking vigorously, but carefully, in a sealed vial. (SAFETY: Be sure that the flask is
sealed well. Oxone ® solution is strongly oxidizing and should not come into contact
with skin.) Dissolve 50 μL of cyclohexene in 2.0 mL of acetone in a small Erlenmeyer
flask. Cool the cyclohexene solution in an icebath, then add the oxone solution dropwise
over 5 minutes with swirling in the icebath. Remove the Erlenmeyer flask from the
icebath and allow the reaction to sit for at least 15 minutes. (This is a good point to begin
the permanganate reaction.) After 15-30 minutes, add about 0.1 mL of conc. HCl to the
reaction dropwise with swirling. Allow the reaction to sit for about 10 minutes, swirling
occasionally.
Procedure Part B: Potassium permanganate reaction: Dissolve 100 mg of KMnO4 in
4.0 mL of 0.1 M NaOH solution in a small Erlenmeyer flask. Cool the KMnO4 solution
in an icebath. Dissolve 50 μL of cyclohexene in 2.0 mL of t-butanol in a separate
container. Quickly add the cyclohexene solution into the potassium permanganate. Swirl
the flask in the icebath for 3-5 minutes. Remove the Erlenmeyer flask from the icebath
and allow to sit for 10 minutes.
Procedure Part C: Thin Layer Chromatography: Obtain a TLC plate. Mark the plate
with four marks, two for each reaction mixture. Spot the crude reaction mixtures lightly.
It may be hard to spot the KMnO4 slurry, but keep trying, you may find it easier if you
use a slightly wider capillary for this one. Allow the plate to dry for a couple of minutes,
or use a heat gun to gently dry the aqueous spots. Develop the plate in a chamber with
ethyl acetate as the eluent. Remove it from the chamber and mark the solvent front. Stain
the plate using anisaldehyde stain, and heat the plate gently to develop the spots. The cis
isomer should stain red, and have an Rf value of ~0.37, the trans isomer should stain blue,
and have an Rf value of ~0.31.
Procedure: Cleanup: Add 2 mL of saturated NaHSO3 solution to quench the oxone
reaction. The quenched oxone reaction, and the permangante reaction should both go
into the container marked “aqueous cyclohexanediol.” If the potassium permanganate
reaction glassware is stained brown, take it to your instructor to be soaked in a dilute
nitric acid bath
Points for discussion:
- Was the oxone reaction stereoselective? What data support your conclusions? If it was
stereoselective, which product was formed preferentially? Did your experimental results
match your pre-lab prediction?
- Was the permanganate reaction stereoselective? What data support your conclusions?
If it was stereoselective, which product was formed preferentially? Did your
experimental results match your pre-lab prediction?