Baran
Heterocyclic
Chemistry
Problem Set
Due Date: Tuesday, April 26th.
Points: 150
6
O
O
NHCOR3
R2N
Provide reasonable mechanisms for the following transformations. (5 points each)
N
1
O
N
O
EtOH
Δ
Me
Δ
N
Me
Me
NHR
R3
N
R1
Me
N
7
2
N
R2HN
NH
HCONH2
N
N
R1
5% NaOH
Me
MeO2C
CO2Me
CO2Me
CO2Me
100 ºC
70%
CO2Me
N
H
Me
N
MeOH
N
H
CO2
Na
N
H
N
H
99% ee
racemic
8
NBoc +
N
N2
xylenes
reflux
R
Boc
N
3
cat DBU
O
NC
R
N
NH2
O
CO2R
Rh(II)
CO2R
9
N
4
Ph
N
O
OHC
X
O
guanidine
free base
NH2
Me
N
H2N
O
A
48 h
50%
O
EtOH, Δ
24 h
H2N
N
Bz
Ph
1 eq. PhCOCl,
N
Ph
3 eq. KCN
or TMSCN
N
NC
N
H
N
B
Me
N
Ph
Me
NMe2
5b Propose a synthesis of A
O
+
N
N
N
NC
+
r.t., then 80 ºC
O
Me
O
Me
10
5
EtOH
Ph
POCl3/DMF
O
OH
CHO
Bz
Ph
35%
CHO
+
Me
N
Ph
1%
Baran
Heterocyclic
Chemistry
Problem Set
11
N
O
CN
CHO
NaOH,
N
MeOH
58%
O
C
11b Propose a synthesis of C
Provide simple syntheses for the following compounds. (5 points each)
(You may not use Pd or other similar metals that achieve cross-coupling.)
Hint: Most syntheses possible in 1–3 steps.
O
3
D
1
CO2Me
N
F
2
Ph
12
Me
O
Me
pulegone
NH2
toluene,
reflux,
NH2
4 days
68%
+
Me
Me
N
CO2Me
N
H
N
CO2H
N
Me
N
H
NHMe
Me
F
4
Br
5
N
Me
Advanced problems in heterocyclic chemistry (10 points each).
1
Treatment of quinolizinium bromide with two equivalents of piperidine gives a high yield of
a product E, C14H18N2. Reaction of E with phenacyl bromide followed by quenching of
the reaction mixture with water gives a product F which was originally claimed to be 3benzoyl-2-vinylindolizine. Subsequent reinvestigation of the structure of F, however,
showed that it was in fact 3-(2-phenyl-1-indolizinyl)prop-2-ene-1-al. Deduce the structure
of E and give a reasonable explanation for the conversion of E into F.
CHO
Ph
N
6
N
H
N
O
Me
Me
N
9
Br
CONHBn
7
8
Ph
Me
N
N
Me
Ph
N
F
N
N
H
Me
Br
HO2C
10
COMe
WolffKishner
N
11
CO2H
12
N
O
N
Br
O
No Desired Product,
obtained X in 62% yield
Me
Me
Me
Provide the mechanism of formation and structure of X:
1H
O
O
F
Cl
2
OTBS
F
NMR: δ 9.26 (s, 1H), 8.01 (brs, 1H, D20 exchangeable),
7.75 (s, 1H), 2.59 (q, 2H), 2.43–2.20 (m, 4H), 2.35 (s, 3H),
1.56 (m, 4H), 1.24 (t, 3H).
15
Me
13
O
Br
N
H
S
14
S
MeO2C
Me
NO2
H
CO2Me
N
H
Me