Heterocyclic Chemistry Final Examination
June 9th, 2009
Professor Baran
Department of Chemistry
The Scripps Research Institute
Name: ______________________________________
Last 4 digits of your Social Security #: ___________
This is a 2-hour test that you have 4 hours to complete
Please present ONLY your FINAL answers on these sheets
Question 1
< (40 points)
Question 2
< (30 points)
Question 3
< (30 points)
Question 4
< (20 points)
Question 5
< (40 points)
Question 6
< (160 points)
Bonus Question
Total
< (20 points)
< (320 points)
1
Question # 1 (40 points): Please provide the intermediate where indicated and
reasonable mechanisms for the following transformations.
A.
H
MeO2C
NH
N
MeO2C
Me
HN
O
H
N
MeO2C
O
major
Me Me
+
EtOH, reflux
TFA, EtOH, r.t
Me
CO2Me
O
Me
H
N N
CO2Me
Me
O
minor
CO2Me
B.
O
Me
O
O
SOCl2
N
N
N
H
NH2
R.T.
83%
Me
O
S
N
N
N
N
2
C.
SH
Cl
S
S
S
S
S
Et3N, DMF
S
Cl
SH
S
S
S
S
D.
O
O
Me
CO2Et
CN
+
N
H
O
CH2N2
EtOH, Et2O
0 - 24°C
?
DMSO
NH2
N
O
3
Question # 2 (30 points): Tripyrranes are popular building blocks in the construction of
various porphyrinoids. They are used in the synthesis of porphyrins, hexaphyrins,
rubyrins and chlorins. It is known that they are difficult to synthesize. What do you think
could be the potential problems for the synthesis of (1)? Please provide a rational
synthesis of (1) avoiding those “potential problems”.
Me
Me
N
H
NH
HN
(1)
4
Me
Me
Me
N
H
NMs MsN
(2)
Me
O2, MeOH, K2CO3
N
H
N
+
(4)
C28H23N3O
+
(5)
C25H22N2O2
N
OMe
C29H25N3O
(3)
Upon treatment of (2) with K2CO3/MeOH/O2 , three dyes are formed. Both (3) and (4) are
red-violet in solution, while (5) was observed as a strong yellow nonpolar band during
chromatography. Based on the information furnished here and what you have learned
from the class, please provide the structures of (4) and (5).
5
Question # 3 (30 points): Amaryllidaceae alkaloids Amarbellisine (1), Vittatine (2) and
Hippeastrine (3) were isolated from A. belladonna L (an ornamental plant in Egypt).
Please propose a biogenetic hypothesis for the formation of (1), (2) and (3).
OMe
H
O
O
N
MeN
OH
HO
O
O
O
N
OH
O
O
O
Amarbellisine (1)
Vittatine (2)
Hippeastrine (3)
6
Question # 4 (20 points): 1H-Indazol-3(2H)-ones (1) are known to exhibit a wide range
of biologically and pharmaceutically relevant properties and are reported to exihibit
analgesic, antitumor, anticancer and anti-inflammatory activities. In order to synthesize
(1), Kurth and co-workers discovered the following interesting transformation (Scheme
1). Please provide the mechanism based on the results shown below. (Org. Lett. ASAP)
It may be helpful to consult the following (Table 1, Table 2 and Figure 2) as you devise a
mechanism.
7
8
Question # 5 (5 points each, 40 each): Please provide the products for the following
transformations.
A.
NHCbz
O
156°C
+
N
H
B.
O
Me
H2SO4
N
NO2
Me
C.
ClCO2Et
N
N
Me2C=C(OTMS)OMe
D.
N
N
N
N
95°C
9
E.
H3N Cl
NH
Cl
PhCHO, KOH
!
N
H
F.
NC
Ph
H2N
NH
NH2
MeO
N
EtONa, EtOH
O
G.
O
NHTs
EtO P
OEt
N
S
CHO
2 eq NaH
H.
CO2Me
t
BuONO
NHAc
95°C
10
Question # 6: (10 points each, 160 points) This is the grand finale. Based on everything
you have learned, each one of these should take 60 seconds to conceive and 4 minutes to
execute on paper. Thus, please provide syntheses of the following heterocycles from
simple starting materials:
A.
N
N
Cl
N
N
N
Cl
B.
OMe
Me
Me
N
N
S
MeO
N
N
O
C.
N
CO2Et
N
N
MeO
O
11
D.
O
Me
Me
N
Me
N
N N
F
E.
Cl
NAc
O
N
N
N
N
N
F
F.
N
N
N
N
N
F
Me
12
G.
Cl
MeO
N
HN
N
N
N
14C *
N
N
N
Et
O
NHCH3
H.
N N
N
N
N
O
Me
O
N
N N
Me
I.
O
S
N
O
N
H
13
J.
MeO2C
N
S
O
N
Me
N
CO2Me
O
K.
S
O
N
N
N
N
Me
L.
O
N
N
H
N
N
O
14
M.
N O
O
OH
F
N
N.
S
N
N
MeO2C
Me
CF3
14C*
N
H
CO2Me
Me
O.
Me
N
O
N
N
O
N
S
Ph
O
15
P.
NH2
OH
HO2C
N
O
N
N
N
N
16
Bonus Question: (20 points) The Moore group at Scripps Institute of Oceanography
recently disclosed their effort at elucidating the mechanism of rearrangement of an aryl
diazoketone to afford the pyridazine natural product azamerone. Please provide a
pathway for this rearrangement.
O
OH
O
Me
Cl
Cl
Cl
Me
O
O
N
N
O
Me
Me
O
Cl
N
Me
N
O
HO
Me
Me
Me
Me
OH
Me
Cl
Me
Me
It was a joy to have each one of you in class! Have a great summer!
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