Massachusetts Institute of Technology
Dr. Kimberly L. Berkowski
5.13, Fall 2006
Organic Chemistry II
EXAM #4 MORE PROBLEMS
DO THESE PROBLEMS BEFORE THE OTHER
SET OF EXTRA PROBLEMS!
(they are more relevant to the exam material)
What to expect on Exam #4:
1. pKas of ketones, diketones, esters, etc.
2. ~3 Transformations – supply missing reagents
3. ~10 Transformations – supply missing product
4. ~2 Mechanisms
5. ~2 Synthesis
What NOT to expect on Exam #4:
1.
Determine mechanism by crossover and stereochemical experiments
(end of Friday’s lecture)
2.
Neighboring Group Participation – Do not work through problems
#8, 24 & 25 on the Extra Problem Set.
1. Please provide a detailed mechanism for the following transformation. Show all
arrow pushing.
O
O
O
O
H
OMe
cat. MeO
+
MeO
OMe
OH
O
O
OH
O
OMe
O
H
OMe
O
O
O
OMe
O
OH
O
H
O
OMe
O
OMe
O
OMe
O
O
O
OMe
H
HO
OMe
H
O
H
H
CO2Me
O
O
O
O
O
O
OMe
H
O
O
O
Figure by MIT OCW.
1
2. (10 points) Please provide a detailed mechanism for the following transformation.
Show all arrow pushing.
O
OMe
Me
Me
Me
Me
Me
1. MeMgBr
2. H3O+
O
Me
Me
Me
MgBr
Me
Me
H2O
O
OH
H
H
O
Me
OMe
Me
Me
Me
Me
Me
Me
H2O
H
H
HO
Me
OMe
Me
Me
MeO
OH
Me
Me
Me
Me
Me
PT
H2 O
Me
Me
OMe
OH2
Me
Me
Me
Me
Me
Me
Me
OR:
OMe
Me
Me
Me
MeO
Me
O
H2 O
Me
Me
H2 O
Me
Me
Me
O
Me
Me
Figure by MIT OCW.
Me
2
3. (10 points) Please provide a detailed mechanism for the following transformation.
Show all arrow pushing. Hint: This mechanism is from problem set 6.
O
O
1. NaOMe, MeOH
2. H+ workup
O
Me
O
Me
OMe
H
O
O
O
OMe
Me
Me
O
O
OMe
O
OMe
O
H
O
Me
Me
O
O
OMe
Me
Figure by MIT OCW.
3
4. (10 points) Diastereomers A and B provide different products upon diazotization.
Please explain why only one product is formed selectively in each reaction. Your
explanation should include a 3-dimensional mechanism for the formation of each
product from the corresponding diazonium salt.
OH
OH
O
NaNO2
HCl
NH2
t-Bu
t-Bu
N2
t-Bu
A
O
OH
OH
NaNO2
H
HCl
t-Bu
NH2
t-Bu
N2
t-Bu
B
In the concerted Tiffeneau-Demjanov rearrangement, the migrating bond must be antiperiplanar
to the leaving group.
(A)
H
O
H
H
:B
-N2
OH
product
N2
H
(B)
OH
O
N2 H
:B
-N2
H
product
H
H
(Bolded bonds are antiperiplanar)
Figure by MIT OCW.
4
5. Please provide a detailed mechanism for the following transformation. Show all
arrow pushing.
O
O
Think about common
disconnection...
cat. -OH
H2O
Me
Me
Me
retroaldol
(aldol)
O
O
≡
O
O
O
O
O
H
OH
O
OH
OH
OH
OH
O
O
O
H2 O
O
H
O
O
O
OH
O
Me
HO
HO
H-OH
Me
H
O
O
OH
O
O
Target
Figure by MIT OCW.
5
6. Please provide a detailed mechanism for the following transformation. Show all arrow
pushing.
O
Cl
OH
O
O
O
O
O
Ar
O
O
H
O
O
HO
O
H
O
O
Ar
O
O
O
Ar
Figure by MIT OCW.
6
7. Please provide a synthesis of the indicated compound. All of the carbon atoms
should be derived from methyl acetate.
Target
O
O
Me
Me
methyl acetate
Me
O
O
O
+
OMe
OMe
Me
O
O
MeO
OMe
O
H+
1 equiv
MeO-
MeO
1. 1 equiv 2.
Br
NaOMe
(below)
O
O
O
O
O
1. 1 equiv
NaOMe
H3O, Δ
2.
MeO
Br MeO
(below)
O
O
H3O
OMe
+
MeOH
PBr3
OH
1. LiAlH4
2. workup
MeBr
OH
PBr3
Br
Figure by MIT OCW.
7
8. Please provide a synthesis of the indicated compound. All of the carbon atoms
should be derived from isopropanol.
Target
OH
OH
Me
Me
isopropanol
OH
OH
PCC
PBr3
O
OH
LDA
(1 equiv.)
Br
O
(below)
Br
1. LiAlH4
2. workup
Target
OR:
OH
PCC
O
O
1. cat. -OH
2. Δ
H2
Pd/C
O
1. LiAlH4
2. workup
Target
Figure by MIT OCW.
8
9. (12 points) Please provide a synthesis of the indicated compound. All of the carbon
atoms should be derived from methyl acetate. You will receive partial credit for a
complete retrosynthesis
Target
O
O
Me
Me
O
OMe
methyl acetate
O
O
+
Me
OMe
O
1. 1 equiv.
NaOMe
2. H+ wkup
OMe
Me
O
OMe
1. 1 equiv.
NaOMe
2. EtBr
O
O
O
O
H3O+
Δ
O
1. 1 equiv.
NaOMe
OMe
2. EtBr
OMe
mCPBA
Target
Figure by MIT OCW.
9
10. (12 points) Please provide a synthesis of the indicated compound. All of the
carbon atoms should be derived from dimethyl malonate and alcohols containing
three or fewer carbons. You will receive partial credit for a complete retrosynthesis.
Target
O
O
O
O
HO
MeO
MeO
O
OMe
alcohols containing
three or fewer carbons
dimethyl malonate
OH
O
MeOH
O
PCC
PCC
1. cat. H+, excess
formaldehyde
O
2. H+, Δ
H
H
O
O
O
1. 1 equiv.
NaOMe
2.
MeO
R
O
MeO
O
O
O
OMe
1. NaBH4
O
MeO
OMe
OH
2. workup
OMe
cat. H+
O
O
MeO
Figure by MIT OCW.
10