Photoredox Asymmetric Nucleophilic Dearomatization of Indoles with Neutral Radicals

Abstract

The dearomatization of indoles represents the most efficient approach for accessing highly valued indolines. The inherent nucleophilic reactivity of indoles has dictated indole dearomatization development in both 1e– and 2e– processes. However, the dearomatization of electron-deficient indoles has been challenging. Herein, we introduce a conceptually distinct photoredox-mediated Giese-type transformation strategy, which is generally used for the conjugate addition of radicals to simple α, β-unsaturated systems, for chemoselectively breaking C═C bonds embedded in the aromatic structure. Moreover, highly diastereoselective addition of challenging neutral radicals has been achieved by Oppolzer camphorsultam chiral auxiliary. Structurally diverse amine-functionalized chiral indolines carrying distinct functional and stereochemical diversity are produced from a wide array of amines as radical precursors. Furthermore, the mild, powerful manifold is capable of the late-stage modification of complex natural products and pharmaceuticals. DFT studies are performed to elucidate the observed stereochemical outcomes.