Selective ring contraction of 5-spirocyclopropane isoxazolidines mediated by acids.
Thermolysis of 3,4-cis ring-fused 5-spirocyclopropane isoxazolidines 16, 18-21, 33, 34, 38a, and 61, in the presence of a protic acid at 70-110 degrees C, yielded 3,4-cis ring-fused azetidin-2-ones 22-26,41, 42, 46, and 62 with concomitant extrusion of ethylene, in good yields. So far, the collected evidences strongly support a mechanism started by a homolytic cleavage of the protonated N-O bond for the rearrangement of 5-spirocyclopropane isoxazolidines to beta-lactams. Some different competitive pathways can then follow depending on the stability or the stereoelectronic properties of cationic diradical intermediates. The two-step process, intramolecular 1,3-dipolar cycloaddition/thermal rearrangement under acidic conditions, represents a general synthesis of a new class of 3,4-cis-fused bicyclic azetidin-2-ones starting from easily available compounds such as amino acids, hydroxy acids, and dicarbonyl or amino alcohol derivatives.
Cordero
Franca M
FM
Dipartimento di Chimica Organica Ugo Schiff, Università degli Studi di Firenze, via della Lastruccia 13, I-50019 Sesto Fiorentino, Florence, Italy. franca.cordero@unifi.it
Pisaneschi
Federica
F
Salvati
Maria
M
Paschetta
Valentina
V
Ollivier
Jean
J
Salaün
Jacques
J
Brandi
Alberto
A