heterocyclic chemistry final examination june 9th, 2009 professor
TRANSCRIPT
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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 < (20 points)
Total < (320 points)
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Question # 1 (40 points): Please provide the intermediate where indicated and reasonable mechanisms for the following transformations. A.
HN
HN
Me
Me O
O
TFA, EtOH, r.t
CO2MeMeO2C
EtOH, reflux
N
NH
H
O
Me Me
MeO2C
MeO2C
HN NMe
Me
O
CO2Me
CO2Me
+
major
minor
B.
N
N NH
NH2
Me
O
O
N
N
Me
O
O
N
N
SSOCl2
R.T.
83%
3
C.
S
S Cl
Cl
SH
SH
S
S
S
S
S
S
S
S
Et3N, DMF
D.
NH
O
CN
O O Me
+ CH2N2
EtOH, Et2O
0 - 24°C?
DMSO
N O
NH2
CO2Et
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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”.
NH
Me Me
NH HN
(1)
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NH
Me Me
NMs MsN
(2)
O2, MeOH, K2CO3NH
Me Me
N N
(3)
OMe
C29H25N3O
(4)C28H23N3O
(5)
C25H22N2O2+ +
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).
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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).
O
ON
HO
H
OMe
Amarbellisine (1)
O
ON
Vittatine (2)
OH
O
OO
OH
Hippeastrine (3)
O
MeN
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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.
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Question # 5 (5 points each, 40 each): Please provide the products for the following transformations. A.
NH
NHCbz
O 156°C+
B.
NO2
N
O
Me
Me
H2SO4
C.
NN
ClCO2Et
Me2C=C(OTMS)OMe
D.
N N
N
N
95°C
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E.
NH
NH
ClH3N Cl PhCHO, KOH
!
F.
NO
PhNC
MeO
NH2
H2N NH
EtONa, EtOH
G.
P NNHTsO
EtOOEt
SCHO
2 eq NaH H.
NHAc
CO2Me
tBuONO
95°C
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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
N
N N
Cl
Cl
B.
N N
N
SN
OMeO
Me
Me
OMe
C.
N
N
MeO
N
O
CO2Et
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D.
N
O
Me
Me
N N
N
Me
F E.
N
N
N
N
N
NAc
O
F
Cl
F.
N
N N
N
Me
N
F
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G.
14CN
N
N
NNHN
N
Et
N
O
NHCH3
Cl
MeO
*
H.
N
N
NN
O
N N
N
ON
Me
Me
I.
N
NH
O
O
S
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J.
N CO2Me
N
S
N
O
MeO2C
O
Me K.
NMe
N
N
N
S
O
L.
NH
NN N
O
O
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M. N
O
O
N
OH
F
N.
NH
14C*MeO2C CO2Me
Me Me
N
N
S
CF3
O.
N
NN
S
O
O
NO
Me
Ph
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P.
N
ON
N
NN
OH
HO2C NH2
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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
N
N
O
O
O
Me
OHCl
Me
Cl
Me
Me
Me
Me
N
NO
O
Cl
Me
Me
O Me
HO
Me
Me
Cl
OH
Me
Cl
It was a joy to have each one of you in class! Have a great summer!
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