Organocatalyzed aza-Payne-type rearrangement of epoxy amines and carbon dioxide for efficient construction of oxazolidinones

Abstract

The aza-Payne-type rearrangement reaction, employing epoxy amines and carbon dioxide (CO₂), offers an atom economical method for synthesizing 5-hydroxymethyl oxazolidinones. Traditionally, alkaline catalysts are primarily utilized for this transformation. In this work, a halide-free pyridinolate based binary organocatalyst was developed for this transformation under atmospheric pressure. The ion pair organocatalyst consists of a positively charged hydrogen-bond donor (HBD⁺) and a negatively charged hydrogen bond acceptor (HBA⁻). These HBD⁺/HBA⁻ ion pair catalysts were generated through the deprotonation of weakly acidic 2-, 3-, and 4-hydroxy pyridine (4-HOP) using super strong nitrogen bases (i.e. TBD, MTBD, DBU, TMG, and DMAP). The reaction achieved high selectivity for oxazolidinones, with minimal cyclic carbonate formation. Seven ion pair catalysts were evaluated for catalyzing the aza-Payne-type rearrangement reaction of epoxy amine 1a and carbon dioxide at 80 °C, using a 5 mol% catalyst loading and a carbon dioxide pressure of 0.1 MPa. Among them, the TBDH⁺/4-OP⁻ ion pair catalyst exhibited the best performance, achieving a high yield of oxazolidinones (84%) in 1 hour. A total of 14 oxazolidinones were synthesized with yields ranging from 72% to 97% under mild conditions (0.1 MPa CO₂, 60–80 °C). The dual activation mechanism of the catalyst was confirmed through NMR titration and control experiments. As a bifunctional catalyst, the ion pair polarized the oxygen atom of epoxy amines via H-bonding with N⁺–H, while the phenolate anion activated the N–H bonding of epoxy amines simultaneously, facilitating the subsequent insertion of carbon dioxide. This approach offers a new method for synthesizing oxazolidinones using organic ion pair catalysts, with promising potential for broader applications.