Enantioselective Access to 3-Azabicyclo[3.1.0]hexanes by CpxRhIII Catalyzed C-H Activation and Cp*IrIII Transfer Hydrogenation

Rigid saturated nitrogen-containing scaffolds such as 3-azabicyclo[3.1.0]hexanes are very important and frequently occurring motifs in biologically active compounds. We disclose a flexible two-step protocol for their efficient and selective access. A tailored C*Rh-III catalyst promotes alkenyl C-H functionalization of N-enoxysuccinimides engaging in rare cis-cyclopropanation of acrolein to access disubstituted cis-cyclopropanes in high enantio- and diastereoselectivity. Subsequently, in the presence of a broad range of primary amines, the dicarbonyl cis-cyclopropanes are efficiently and completely diastereoselectively cyclized by a Cp*Ir-III catalyst via an iterative aminative transfer hydrogen to an exquisite set of substituted 3-azabicyclo[3.1.0]hexanes.

Automated summary

In this study, a flexible two-step protocol for the efficient and selective synthesis of rigid saturated nitrogen-containing scaffolds was disclosed. The method involves alkenyl C-H functionalization and cyclization reactions mediated by C*Rh-III and Cp*Ir-III catalysts, respectively, leading to the synthesis of diverse substituted 3-azabicyclo[3.1.0]hexanes.