3-Diazopiperidine-2,4-diones as Convenient Precursors to Rare Polysubstituted Spiro Bis-β,γ-lactams and 2-Oxopyrrolidine-3-carboxylic Acid Derivatives via the Thermally Promoted Wolff Rearrangement

Abstract

Herein, we describe a diastereoselective and straightforward synthetic approach to polysubstituted spirocyclic bis-lactams bearing both β- and γ-lactam cores with diverse substitution patterns. The method developed is based on a microwave-assisted Wolff rearrangement/Staudinger [2 + 2] cycloaddition sequence involving 3-diazopiperidine-2,4-diones and imines. The corresponding reaction tolerates a wide range of functionalities in both substrates, giving the target bis-lactams in generally high yields. The synthetic utility of the thermally promoted Wolff rearrangement has been extended to the interaction of 3-diazopiperidine-2,4-dione-derived ketenes with various nucleophiles leading to derivatives of 2-oxopyrrolidine-3-carboxylic acids. Our findings potentially pave an avenue for designing new compounds with a high degree of medicinal relevance by means of the processes studied.