Click chemistry is a chemical concept introduced by K. B. Sharpless in 2001 and... Heating B in pyri — Physical Chemistry — Thermodynamics Chemistry Question
Click Chemistry
Click chemistry is a chemical concept introduced by K. B. Sharpless in 2001 and...
Heating B in pyridine yields C. During this transformation, compounds B and C retain their absolute configurations.
Scheme 8.1:
TsCl (1 eq), Et3N (1.2 eq) Pyridine, heatA B
CH2Cl2, 0 oC
C
Reaction of C with sodium azide in aqueous acetonitrile gives a mixture of enantiopure regioisomers D and E in a ratio of 3 : 1 (Scheme 8.2). On the other hand, the compound B affords E as the sole product under the same condition.
Scheme 8.2:
C D E+
NaN3 aq. CH3CN
reflux
B E NaN3
aq. CH3CN
reflux
Part I: Compounds D and E are separately subjected to NaH mediated reaction with 3-bromoprop-1-yne to afford F and G, respectively (Scheme 8.3). Heating F and G separately in toluene gives the bicyclic products H and I, respectively.
Scheme 8.3:
D F
E
Br
NaH, THF
toluene
reflux
Br
NaH, THF G toluene
reflux I
H
Part II: Reaction of D and E separately with dimethyl acetylenedicarboxylate in water at 70 °C forms the optically active monocyclic regioisomers J and K, respectively (Scheme 8.4). Subsequent treatment of J and K with NaH gives final bicyclic products L and M, respectively, both having the formula C13H11N3O4.
Scheme 8.4:
NaH, dry THFD J
70 oC
L+ CO2CH3H3CO2C H2O
NaH, dry THFE K
70 oC
M+ CO2CH3H3CO2C H2O
reflux
reflux
Draw the structures of B and C with the correct stereochemistry. Use dashed-wedged line notation throughout this problem.
Model Answer
B
O
O
S
OH
Ph CH3
O
OH
Ph
O
Ts
or
C
O
Ph
Draw the structures of D and E with the correct stereochemistry.
Model Answer
D
Ph
N3
OH
E
Ph
N3
OH
Draw the structure of compounds F, G, H and I with the correct stereochemistry.
Model Answer
F
Ph
N3 O
G
Ph
N3
O
H
N NN
O
Ph
I
N NN
O
Ph
Draw the structures of compound J, K, L and M with the correct stereochemistry.
Model Answer
J
CO2CH3
CO2CH3N N
N
Ph
OH
K
CO2CH3
NN N
Ph
H3CO2C
OH
L
CO2CH3
N N
N
Ph
O
O
M
N NN
O
Ph
O CO2CH3