Divergent Synthesis of Meyers’ Lactams and Medium Lactams via Cyclocondensation of γ-Ylidene-Butanolides with Chiral Amino Alcohols

A novel methodology for constructing Meyers' lactams (pyrrolidino-oxazolidines), related to biologically potent natural and synthetic scaffolds, has been developed via an unprecedented tandem cyclocondensation of chiral 2-amino alcohols and γ-ylidene-butanolides. The process proceeds through the initial formation of an ene-lactam intermediate, followed by a Bro̷nsted acid (PPTS)-catalyzed ring closure. Under stoichiometric amounts of a Lewis acid (TiCl₄), the same set of building blocks affords medium lactams featuring eight-membered ring systems with an <i>exo</i>-enol ether segment. This divergent synthetic strategy enables the efficient generation of a library of Meyers' lactams and medium lactams with good yields and diastereoselectivity.