Synthesis of Polycyclic Imidazolidinones via Cascade [3+2]-Annulation of β-Oxo-acrylamides with Cyclic N-Sulfonyl Imines

An Et3N-catalyzed cascade [3 + 2]-annulation of beta-oxo-acrylamides with cyclic N-sulfonyl ketimines or sulfamate-derived imines is developed under mild reaction conditions, which provides a concise and efficient route to access valuable sultam- or sulfamidate-fused imidazolidinone derivatives in good to excellent yields (80-95% yields) with excellent diastereoselectivities (>20:1 drs). The current protocol features atom economy, a transition-metal-free process, and broad functional group tolerance. Moreover, the asymmetric variant of the [3 + 2]-cycloaddition reaction was achieved in the presence of diphenylethanediamine or quinine-based bifunctional squaramide organocatalysts C-1 and C-11, giving the corresponding chiral polycyclic imidazolidinones in 68-90% yields with 25-94% ees and >20:1 drs in all cases.

Automated summary

An Et3N-catalyzed cascade [3 + 2]-annulation of beta-oxo-acrylamides with cyclic N-sulfonyl ketimines or sulfamate-derived imines has been developed, providing a concise and efficient route to valuable sultam- or sulfamidate-fused imidazolidinone derivatives in good to excellent yields with excellent diastereoselectivities. The protocol features atom economy, a transition-metal-free process, and broad functional group tolerance. Moreover, the asymmetric variant of the [3 + 2]-cycloaddition reaction was achieved using chiral organocatalysts, giving the corresponding chiral polycyclic imidazolidinones in good yields with high enantioselectivities and diastereoselectivities.