Ni(II)-Catalyzed Asymmetric Nitration of Oxindoles: Construction of Cipargamin Analogues

The efficient stereoselective nitration of sp(3) carbons, especially in an asymmetric manner, remains a formidable challenge. Here we report an example of nickel-catalyzed asymmetric nitration reaction, delivering chiral oxindoles bearing a tertiary nitro group in good yields with high enantioselectivities (up to 83% yield and 95% ee). Diverse enantioenriched 3-nitro oxindoles were prepared from readily available oxindoles efficiently, benefiting the synthesis of chiral 3-amino oxindoles. Notably, the synthetic potential of this asymmetric nitration method was further demonstrated by constructing analogues of Cipargamin, a potent antimalarial agent. Preliminary mechanistic studies supported a radical process involved in this transformation.

Automated summary

This study reports a nickel-catalyzed asymmetric nitration reaction that successfully synthesized chiral oxindoles with a tertiary nitro group in good yields and high enantioselectivities. The resulting products can be used for the synthesis of chiral 3-amino oxindoles and demonstrate the synthetic potential for analogues of the antimalarial agent Cipargamin.