Novel diastereoselective synthesis of bicyclic beta-lactams through radical cyclization and their reduction toward 2-(1-alkoxy-2-hydroxyethyl)piperidines and 2-(1-alkoxy-2-hydroxyethyl)azepanes.
1-Allyl- and 1-(3-phenylallyl)-substituted 4-(2-bromo-1,1-dimethylethyl)azetidin-2-ones were transformed into 3-substituted 7-alkoxy-5,5-dimethyl-1-azabicyclo[4.2.0]octane-8-ones through radical cyclization by means of n-tributyltin hydride and AIBN in toluene with excellent diastereocontrol (>or=99%). The radical cyclization of 4-(2-bromo-1,1-dimethylethyl)-1-(2-methylallyl)azetidin-2-ones afforded 8-alkoxy-3,6,6-trimethyl-1-azabicyclo[5.2.0]nonan-9-ones in good diastereomeric excess (75-78%). The reductive ring opening of 1-azabicyclo[4.2.0]octane-8-ones and 1-azabicyclo[5.2.0]nonan-9-ones with lithium aluminum hydride resulted in novel 2-(1-alkoxy-2-hydroxyethyl)piperidines and -azepanes, which were isolated as single isomers.
Leemans
Erika
E
Department of Organic Chemistry, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium.
D'hooghe
Matthias
M
Dejaegher
Yves
Y
Törnroos
Karl W
KW
De Kimpe
Norbert
N
D001381:Azepines / Q000737:chemistry*; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis*; D003500:Cyclization; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D010880:Piperidines / Q000737:chemistry*; D013237:Stereoisomerism; D047090:beta-Lactams / Q000138:chemical synthesis*
D001381:Azepines; D001643:Bridged Bicyclo Compounds; D010880:Piperidines; D047090:beta-Lactams