ol5b02218_si_001.cif (24.87 kB)
Total Synthesis of (±)-Eucophylline. A Free-Radical Approach to the Synthesis of the Azabicyclo[3.3.1]nonane Skeleton
dataset
posted on 2015-09-18, 00:00 authored by Haitham Hassan, Shireen Mohammed, Frédéric Robert, Yannick LandaisThe first total synthesis
of eucophylline was reported in 10 steps
and 10% overall yield. The naphthyridine core of eucophylline was
prepared through the coupling between a strained azabicyclo[3.3.1]nonan-2-one
and a trisubstituted benzonitrile, followed by a cyclization of the
corresponding amidine. This coupling reaction was shown to proceed
through a stable bicyclic chloroenamine intermediate. The azabicyclo[3.3.1]nonan-2-one
skeleton was in turn accessible through a straightforward sequence
including a free-radical three-component olefin carbo-oximation as
a key step.