Chemistry Reference
In-Depth Information
CO
2
Et
CO
2
Et
TfOH
CHCl
3
0ºC
H
N
3
N
221
222
CO
2
Et
CO
2
Et
H
+
NH
NH
2
223
224
(70%)
SCHEME 10.34.
through recourse to molecular mechanics and
ab initio
molecular orbital calcula-
tions, attributed to a decrease in the conformational rigidity of the nitrenium ion
intermediate.
Returning to Abramovitch's study of the aporphine ring system (Scheme 10.35),
while the regioselectivity and efficiency of the carbocyclization route to these
products left much to be desired, the unanticipated formation of 16-membered
macrocycle
, is remarkable.
Abramovitch attributed the formation of this strained product to a favorable inter-
action, or “recognition”, between the nitrenium ion (or its protonated azide precursor
226
227
, upon acidolysis of
p-
substituted aryl azide
225
) and the electron-donating
O
-benzyl group, which would lead to a lowering of
the activation energy of this remarkable cyclization.
Intriguingly, Abramovitch subsequently demonstrated the viability of this nitre-
nium ion macrocyclization strategy in other systems, including aryl azides
228
and
229
, which upon exposure to TfOH-TFA underwent intramolecular electrophilic
MeO
MeO
MeO
N
N
N
O
Me
O
Me
TFA
BnO
Me
H
rt
N
3
H
N
H
225
226
N
2
227
(30%)
SCHEME 10.35.
