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

The
efficient stereoselective nitration of sp3 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.