Chapter 33 — Stereoselective reactions of cyclic
compounds: Part B
- Iodolactonizations and stereoselectivity
- Baldwin’s rules for ring closure
- Epoxidations and stereoselectivity
Reading guide:
Ch. 18 Read only pages 457–474
Ch. 33 Skip section on unsaturated 6-membered rings (858–861)
A new reaction for making cyclic compounds:
Iodolactonization
Remember reactions of alkenes through bromonium ion intermediates?
RO
Br
Br
Br
RO–
Br
(±)
Br–
Iodine reacts with alkenes to make “iodonium ions” in the same way… and
an internal carboxylate the right number of atoms away can attack to give
a 5, 6, or 7-membered cyclic ester (“lactone”).
OH
O
I2, NaHCO3
O–
I
O
O
I
O
Two points on the stereoselectivity of iodolactonizations
O
O
OH
O
I2, NaHCO3
(±)
I
O
O
O
I2, NaHCO3
Because this is an Sn2-like reaction
proceeding through a iodonium
intermediate, the attacking oxygen and
the iodine must end up on opposite sides
of the alkene.
OH
Me
I
Me
H
H
I2, NaHCO3
Me
In a cyclic starting material, the
carboxylate is “tethered” to one side; it
can only reach one face of the alkene,
so that’s the face that ends up with the
oxygen atom.
I
Me
H
HO
O
O
H
O
O
O
OH
I2, NaHCO3
H
O
O
O
I
I
H
What can you do with an iodolactone?
1) Use the iodoalkyl part as an alkylating agent
OH
I2, NaHCO3
O
I
RO–
O
O
RO
O
O
2) Eliminate the iodine atom to give an alkene (DBN is a non-nucleophilic base)
O
O
OH
Me
O
I2, NaHCO3
Me
(±)
I
O
O
DBN
Me
(±)
3) Hydrolyze the ester, and then use the resulting hydroxy-iodo compound to
form an epoxide
O
O
I2, NaHCO3
O
OH
Me
NaOH,
H2O
O–
–O
O
I
Me
O–
I
Me
O
O
Me
What can you do with an iodolactone?
4) Reduce away the iodine atom via a free-radical methodology.
HO
O
O
I2, K2CO3
H
O
O
O
Bu3SnH, AIBN
H
I
H
An example of stereoselectivity that is not based on
steric repulsion
As expected, epoxidation by a peracid such as mCPBA normally chooses the side
of the alkene with a minimum of steric hindrance…
OMe
OMe
mCPBA
OMe
O
+
O
minor
major
… but this can be reversed when a neighbouring alcohol is present in the allyllic
position. The alcohol, by hydrogen bonding to the peracid, can direct the reagent
to the same face of the alkene as the alcohol.
OH
OH
mCPBA
OH
O
minor
+
O
major
VO(acac)2, t-BuOOH also
makes epoxides from alkenes,
and is directed even more
strongly to the same face as a
neighbouring alcohol (CGWW
pg. 877–888)
I can make that! (Ch. 33)
4- and 5-membered rings with stereochemistry
O
Bn
O
Me
Me
Bn
O
O
O
O
O
O
O
O
Ph
Bu
6-membered rings with stereochemistry
OH
OH
Me
I can make that! (Ch. 33)
Iodolactones/Lactones in general (with or without subsequent iodine elimination)
O
O
or
O
O
O
OH
I
Epoxides — using mCPBA, VO(acac)2/t-BuOOH, or two-step methods that rely
on bromoalcohol or iodoalcohol intermediates
To pick the right epoxidation method, pay attention to starting material and
product stereochemistry!
or
O
H
HO
R
R
O
HO
O
HO
Br
H
or
H
HO
I
H