jo802459j_si_001.pdf (3.26 MB)

Diastereoselective Synthesis of Bicyclic γ-Lactams via Ring Expansion of Monocyclic β-Lactams

Download (3.26 MB)
journal contribution
posted on 20.02.2009 by Stijn Dekeukeleire, Matthias D’hooghe, Norbert De Kimpe
cis-4-(1-Chloro-1-methylethyl)-1-(ω-hydroxyalkyl)azetidin-2-ones were diastereoselectively transformed into novel trans-1-aza-4-oxabicyclo[3.3.0]octan-8-ones and trans-1-aza-5-oxabicyclo[4.3.0]nonan-9-ones upon treatment with 1 equiv of AgBF4 and pyridine in toluene via intramolecular nucleophilic trapping of N-acyliminium intermediates by the hydroxyl moiety. Additionally, the corresponding aza-analogues of the aforementioned bicyclic γ-lactams (i.e., trans-1,4-diazabicyclo[3.3.0]octan-8-ones and trans-1,5-diazabicyclo[4.3.0]nonan-9-ones) were prepared in a convenient way starting from cis-4-(1-chloro-1-methylethyl)-1-{ω-[(tert-butoxycarbonyl)amino]alkyl}azetidin-2-ones applying the same reaction conditions. The intermediate N-acyliminium ions were formed by ring expansion of the starting β-lactams through generation of a transient silver(I)-induced carbenium ion.