Access to Spiro Bis-β-lactams via a Metal-Free Microwave-Assisted Wolff Rearrangement/Staudinger [2+2] Cycloaddition Cascade Involving 3-Diazotetramic Acids and Imines
Vasilisa Krivovicheva, Ivan Lyutin, Grigory Kantin, Dmitry Dar’in
Abstract
Herein, we report the study of the thermally promoted reaction of 3-diazotetramic acids with imines as a rapid route to a novel spiro heterocyclic scaffold, spiro bis-β-lactams (2,6-diazaspiro[3.3]heptane-1,5-diones). The transformation proceeds via metal-free microwave-assisted Wolff rearrangement of the diazo reagent followed by Staudinger [2+2] cycloaddition of the heterocyclic ketenes with Shiff bases. This methodology enables the preparation of diastereomerically pure spiro bis-β-lactams in high yields and provides an avenue for exploring new versions of the privileged β-lactam core for drug design.
Topics & Concepts
ChemistryWolff rearrangementCycloadditionStaudinger reactionReagentCombinatorial chemistryDiazoLactamStereochemistryOrganic chemistryCatalysisSynthesis of β-Lactam CompoundsSynthesis and Catalytic ReactionsCyclopropane Reaction Mechanisms