Iodine-Catalyzed Enantioselective Synthesis of Pyrrolidin-2-ones from β-Lactams

Significance

Reported here is the iodine-catalyzed ring expansion of 4-oxoazetidine-2-carbaldehydes A (β-lactams) in the presence of TBSCN to afford 5-cyano-3,4-dihydroxypyrrolidin-2-ones B (γ-lactams) in good to excellent yield and with moderate to high diastereoselectivity. The proposed catalytic cycle as shown involves aldehyde-iodine coordination followed by C3-C4 bond cleavage, undoubtedly favored by ring strain, which leads to the pyrrolidinium intermediates which, after cyanation, give the 5-cyanopyrrolidin-2-ones B. No ring expansion was observed for β-lactams A with R¹ = non-alkyl and benzyl substituents for which cases only O-silylated cyanohydrins C were obtained. No reaction was observed for the epi- A (C3-epimer) isomer of the β-lactams, which suggest the necessity of the presence of the cis-alkoxy group (R²). The starting β-lactams A were prepared in four steps involving [2+2] cycloaddition as the key step using enantio­pure aldehydes, a potential limitation to this process.