Synthesis of Highly Substituted Cryptophane Derivatives

We
report the synthesis of new cryptophane derivatives 1–4 bearing nine (1, 2) and twelve (3, 4) methoxy substituents.
These compounds represent the first examples of cryptophane derivatives
bearing more than six substituents attached on the benzene rings.
The preparation of these highly substituted cryptophanes was achieved
due to the synthesis of a new cyclo­trisyringyl derivative obtained
from the reaction of a protected syringyl alcohol in the presence
of a catalytic amount of scandium triflate Sc­(OTf)3. This
reaction also provides the protected cyclotetra­syringyl derivative
in low yield (7%), which was fully characterized by 1H
NMR, IR, and X-ray crystallography. In contrast to what is observed
for the crypto­phane-A congener, the synthesis of these highly
substituted cryptophanes gives rise to the two anti- and syn-diastereomers. These compounds have been
fully characterized, and their X-ray structures have been obtained
to ascertain the stereochemistry of these new cryptophane derivatives.