The azomethine ylide strategy for β-lactam synthesis.: Azapenams and 1-azacephams

Reaction of the beta-lactam-based oxazolidinone 5 with N-sulfonylimines provides the exo and endo azapenams 8 in 22-54% yield. The reactivity of 2H-azirines as 1,3-dipolarophiles towards beta-lactam-based azomethine ylides derived from oxazolidinones 5 and 15 has also been evaluated. Azirines 11 and 12a provide cycloadducts 13a, b and 16 respectively, which incorporate the novel 2,6-diazatricyclo[4.2.0.0(2,4)]octan-7-one ring system. These adducts were resistant towards C-N cleavage as the basis of an entry to 1-azacephams (1,5-diazabicyclo[4.2.0] octan-8-ones) 4. The use of the 3-(4-methoxyphenyl)-2H-azirine 19 provides a labile initial cycloadduct, which undergoes in situ ring-cleavage and further reaction to give the 2 : 1 adduct 1-azacepham 22. The initial product is stable when 3-(4-nitrophenyl)-2H-azirine 23 is employed, and cycloadducts 24a and 24b are converted under mild reducing conditions to the 1-azacepham derivatives 25 and 26.