Cyclic Bifunctional Reagents Enabling a Strain-Release-Driven Formal [3+2] Cycloaddition of 2H-Azirines by Cascade Energy Transfer

Petti, Alessia; Karrasch, Mathis J.; Chahar, Preeti; Wessels, Felix H.; Hoelter, Niklas; Boser, Florian; Daniliuc, Constantin G.; Glorius, Frank

Abstract

The energy transfer (EnT)-catalyzed ring opening and further decarboxylation of isoxazole-5(4H)-ones enables the in situ generation of strained 2H-azirines. Subsequent selective C(sp2)–C(sp3) bond cleavage of the azirine intermediate allows a formal [3 + 2] cycloaddition with a wide range of electrophiles, unlocking access to valuable pyrroline-type moieties. Mechanistic experiments in combination with density functional theory (DFT) calculations revealed the unique nature of the EnT-cascade process for the generation and ring opening of the three-membered aza-cycle while providing insight into the regio- and diastereoselectivity of the annulation. This mild and straightforward method ensures the rapid construction of highly substituted cyclic imines, which can be easily converted into pyrrolidines, fused oxaziridines, and biologically relevant β-amino acid precursors.