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?

Br RO Br
Br (±)
Br RO–
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”).

I2, NaHCO3
OH O– O
O
I I
O O
Two points on the stereoselectivity of iodolactonizations

O O
O
OH
I2, NaHCO3 Because this is an Sn2-like reaction
(±) proceeding through a iodonium
I
intermediate, the attacking oxygen and
O the iodine must end up on opposite sides
O
I2, NaHCO3
O of the alkene.
OH
Me I Me
In a cyclic starting material, the
H H carboxylate is “tethered” to one side; it
I2, NaHCO3 can only reach one face of the alkene,
I
so that’s the face that ends up with the
Me H Me
O
H oxygen atom.
HO O O

O O O
H
OH I2, NaHCO3
O O
I I
H
What can you do with an iodolactone?

1) Use the iodoalkyl part as an alkylating agent

I2, NaHCO3 O RO– O
OH O O
I RO
O

2) Eliminate the iodine atom to give an alkene (DBN is a non-nucleophilic base)

O O O
O O
I2, NaHCO3 DBN
OH Me Me
Me
(±) (±)
I

3) Hydrolyze the ester, and then use the resulting hydroxy-iodo compound to
form an epoxide
O
O O NaOH, O– O–
I2, NaHCO3 H2O –O
OH O O
O
Me I Me I Me Me
What can you do with an iodolactone?

4) Reduce away the iodine atom via a free-radical methodology.

HO O O O
O O
I2, K2CO3 Bu3SnH, AIBN

I
H H 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 OMe

mCPBA
O + O

major minor

… 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 OH
mCPBA
VO(acac)2, t-BuOOH also
O + O makes epoxides from alkenes,
and is directed even more
minor major
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 Me O
O O O
O
Me Bn O
O O O Ph
Bu Me

6-membered rings with stereochemistry

OH OH
I can make that! (Ch. 33)

Iodolactones/Lactones in general (with or without subsequent iodine elimination)

O O
O
O or O
I OH

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!
Br I
H H
or or
H H
O HO HO

R R
O

HO
HO
O