Name_______________________________
215 F10-Exam No. 3
Page 2
I. (36 points) Provide in the boxes below a step-by-step mechanism using the curved arrow convention for
each of the following transformations.
O
OCH2CH3
(1)
O
NaOCH2CH3
OCH2CH3
O
Na
HOCH2CH3
+ enantiomer
O
Mechanism:
You need not show Na+ for each step.
OCH2CH3
O
Na
OCH2CH3
O
non-charged diester intermediate
O
OCH2CH3
O
Na
26
(2)
O
O
+
NH2
H3CO
O
O
O
Mechanism:
O
O
O
O
H3CO
H
N
O
+
CO2
+
HO
O
O
O
O
O
H3CO
NH2
O
H3CO
H
N
O
O
10
Name_______________________________
215 F10-Exam No. 3
Page 3
II. (24 points) Provide in the box below a step-by-step mechanism using the curved arrow convention for
the following double Michael-addition reaction [J. Org. Chem. 2010, 75, 7491]. You do not need to
comment on the stereochemical outcome of the reaction.
Ph
O
H3CO
H
+
NaOCH3 (catalytic)
O
HOCH3
H
H3CO
H3CO
O
H3CO
Ph
O
Ph
O
O
Ph
Ph = C6H5
Mechanism:
O
H3CO
H
H3CO
H
Ph
OCH3
O
Ph
O
O
Ph
H3CO
O
H3CO
O
Ph
24
III. (8 points) Consider the predominant form of each amino acid in aqueous solution and identify all of the
ones that meet the criteria described in the boxes by writing the letters corresponding to those structures. It
is possible that some may be used more than once. pKa’s for underlined hydrogens are as indicated.
O
HO
4.07
E
O
H3N
9.47
OH
H 2.10
10.53
H3N
O
K
H3N
8.95
O
2.18
OH
10.07
HO
H
Y
O
8.00
HS
H3N
10.25
2.05
OH
H3N
9.11
2.20
OH
H
12.48
NH2
H2N
N
H
H
C
Those having a net positive charge at pH 6:
Those having a net negative charge at pH 8.5:
Those having no net charge at pH 6:
That having the highest isoelectric point (pI):
R
O
2.01
OH
H3N
9.04
H
Name_______________________________
215 F10-Exam No. 3
Page 4
IV. (10 points) Draw the full structure (including stereochemistry) for the tri-peptide Pro-Val-His (all L
amino acids) in the predominant form it would exist at its isoelectric point. Use the Fischer projections.
Structure at the isoelectric point:
The predominant form of this tripeptide at pH 1
has a net charge of: (circle one)
+2
+1
0
-1
-2
2
The predominant form of this tripeptide at pH 11
has a net charge of: (circle one)
+2
+1
0
-1
-2
6
2
V. (12 points) Complete each of the following transformations as indicated by the data provided.
(1) [J. Org. Chem. 2010, 75, 7869]
N C N
O
O
HOCH2Ph
(DCC)
N
O
N
N
OH
N
CH2Cl2
(solvent)
CH2Cl2 (solvent)
4
4
uncharged intermediate
+
H
N
H
N
O
(2) [J. Org. Chem. 2010, 75, 3027]
NH2
O
O
O
O
O
O
Ph
N
O
O
H2, Pd/C
N
H
N
O
O
O
CH3OH
(solvent)
Ph
4
+ CO2 + 2 CH3Ph
Name_______________________________
215 F10-Exam No. 3
Page 5
VI. (15 points) Complete the following reactions by providing in each of the boxes the structure of the
reagent, intermediate, or product. Indicate stereochemistry for the product/intermediate and if more than one
stereoisomer is formed, draw one structure and write “+ enantiomer” or “+ diastereomer.”
(1)
OCH3
O
O
OCH3
1. NaOCH3 (1 equiv)
2.
Br
NaOCH3
(1 equiv)
Br
(1 equiv)
2
3
+ NaBr + HOCH3
+ NaBr + HOCH3
H3O+
H2
heat
+ CO2 + 2 CH3OH
C7H12O2
3
(2) [Chem. Commun. 2010, 8436]
1.
O
NH3
N
H
O
O
2 equiv
3
OH
O
OCH3
N
N(CH2CH3)3
N
H
2. H3O+ (protonation)
1. KO
(2 equiv)
O
OCH3
2. H3O+ (protonation)
4
+ 2 HO
+ HOCH3
Name_______________________________
215 F10-Exam No. 3
Page 6
VII. (15 points) Complete the following reactions by providing in each of the boxes the structure of the
product or intermediate. Indicate stereochemistry for the product/intermediate and if more than one
stereoisomer is formed, draw one structure and write “+ enantiomer” or “+ diastereomer.”
(1)
1. LiAlH4
tetrahydrofuran
(THF, solvent)
O
O
2. aq NH4Cl
C8H18O2
3
(2) [Org. Biomol. Chem. 2010, 5525]
O
LiAlH4 (excess)
tetrahydrofuran
(THF, solvent)
N
N
O
H3CO
4
(3) [J. Am. Chem. Soc. 2010, 132, 14349]
O
Cl
room
temperature
(PhCH2)2CuLi
OCH3
CH2Cl2
-78 °C
hint:
"intramolecular
ring formation"
lithium enolate
2
C12H14O2
+ LiCl
+ PhCH2Cu
(4) [J. Am. Chem. Soc. 2010, 132, 14064]
O
N
OCH3
1. LiAlH4
tetrahydrofuran
(THF, solvent)
2. H3
O+,
+
H 2O
CH3
C8H14O
3
OCH3
H
N
H
CH3
3