Catalytic Asymmetric Construction of Azabicyclo[2.2.1]heptanes Bearing Two Quaternary Stereogenic Centers via Silver(I)-Catalyzed 1,3-Dipolar Cyclo­addition of Cyclic Azomethine Ylides

Abstract

Ag(I)/TF-BiphamPhos-catalyzed asymmetric 1,3-dipolar cycloaddition reaction of cyclic azomethine ylides with N-substituted maleimides has been developed for the efficient construction of azabicyclo[2.2.1]heptanes, a valuable structural motif for drug discovery, in good yields with high diastereoselectivities (up to 16:1 dr) and excellent enantioselectivities (up to 97% ee). The key feature of the present methodology is that two quaternary stereogenic centers were constructed efficiently among the generated four contiguous stereocenters in the annulation process.