Total Synthesis of (±)-Eucophylline. A Free-Radical Approach to the Synthesis of the Azabicyclo[3.3.1]nonane Skeleton.
The 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.
University of Bordeaux , Institute of Molecular Sciences, UMR-CNRS 5255, 351 cours de la libération, 33405 Talence, France.
Haitham
H
Hassan
University of Bordeaux , Institute of Molecular Sciences, UMR-CNRS 5255, 351 cours de la libération, 33405 Talence, France.
Shireen
S
Mohammed
University of Bordeaux , Institute of Molecular Sciences, UMR-CNRS 5255, 351 cours de la libération, 33405 Talence, France.
Frédéric
F
Robert
University of Bordeaux , Institute of Molecular Sciences, UMR-CNRS 5255, 351 cours de la libération, 33405 Talence, France.
Yannick
Y
Landais
D000473:Alkanes / Q000138:chemical synthesis* / Q000737:chemistry; D000475:Alkenes; D029062:Apocynaceae / Q000737:chemistry; D053961:Azabicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D005609:Free Radicals; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013237:Stereoisomerism
D000473:Alkanes; D000475:Alkenes; D053961:Azabicyclo Compounds; D005609:Free Radicals; C000603714:eucophylline; C017573:nonane