Multifunctional Ag(I)/CAAA-Amidphos Complex-Catalyzed Asymmetric [3+2] Cycloaddition of α-Substituted Acrylamides

Construction of two kinds of prevalent skeletons for chiral pyrrolidines bearing a quaternary stereocenter and bridged dinitrogen heterocycles is a long-standing challenge in synthetic organic chemistry. In this work, we introduce a multifunctional Ag(I)/CAAA-amidphos complex-catalyzed asymmetric [3 + 2] cycloaddition of alpha-substituted acrylamides with iminoesters as a powerful strategy for the construction of 4,4-disubstituted endoamidopyrrolidines (up to 98% yield, m/b > 99:1, 99% ee) and bridged 3,6-diazabicyclo[3.2.1]octanes (up to 97% yield, b/m > 99:1, >99% ee) in high yields with excellent enantioselectivities and ratios of mono- and bicyclic adducts. It was revealed by in situ P-31 NMR and H-1 NMR kinetic experiments analysis that the chiral Ag(I)/CAAA-amidphos complex, as a multifunctional catalytic system through synergistic activation and spatial orientation of the dipole and dipolarophile, first realized the asymmetric [3 + 2] cycloaddition of the poorly reactive alpha-substituted acrylamides.

Automated summary

This study successfully developed an asymmetric [3+2] cycloaddition reaction catalyzed by a multifunctional Ag(I)/CAAA-amidphos complex, enabling the high-yield synthesis of chiral pyrrolidines with quaternary stereocenters and bridged dinitrogen heterocycles with excellent enantioselectivity.