Photoredox-catalyzed diastereoselective dearomative prenylation and reverse-prenylation of electron-deficient indole derivatives

Abstract

Prenylated and reverse-prenylated indolines are privileged scaffolds in numerous naturally occurring indole alkaloids with a broad spectrum of important biological properties. Development of straightforward and stereoselective methods to enable the synthesis of structurally diverse prenylated and reverse-prenylated indoline derivatives is highly desirable and challenging. In this context, the most direct approaches to achieve this goal generally rely on transition-metal-catalyzed dearomative allylic alkylation of electron-rich indoles. However, the electron-deficient indoles are much less explored, probably due to their diminished nucleophilicity. Herein, a photoredox-catalyzed tandem Giese radical addition/Ireland–Claisen rearrangement is disclosed. Diastereoselective dearomative prenylation and reverse-prenylation of electron-deficient indoles proceed smoothly under mild conditions. An array of tertiary α-silylamines as radical precursors is readily incorporated in 2,3-disubstituted indolines with high functional compatibility and excellent diastereoselectivity (>20:1 d.r.). The corresponding transformations of the secondary α-silylamines provide the biologically important lactam-fused indolines in one-pot synthesis. Subsequently, a plausible photoredox pathway is proposed based on control experiments. The preliminary bioactivity study reveals a potential anticancer property of these structurally appealing indolines.

Decatungstate‐Photocatalyzed Diastereoselective Dearomative Hydroalkylation of Indoles

“…Interestingly, when reacting a substrate functionalized by a C3-prenyl ester, we did not observe the generation of a C3-prenylated indoline -resulting from dearomative alkylation followed by Ireland-Claisen rearrangement -in contrast to an elegant transformation reported by Feng, Liu, and co-workers. [17] Instead, compound 4 l was exclusively formed. Besides, 7azaindole was compatible, furnishing 4 m with high yield and complete diastereoselectivity.…”

Photochemical dearomative skeletal modifications of heteroaromatics

“…Recently, Liu, Feng and co-workers documented the preparation of prenylated and reverse-prenylated indolines 266 via photoredox catalysed Giese radical addition/Ireland–Claisen rearrangement from N -Ts prenyl/reverse-prenyl indole 3-carboxylate 264 ( Scheme 28 ). 92 Mechanistically, α-silylamine 265 was oxidized by excited state 4CzIPN, producing α-amino radical 271 and TMS + . Subsequently, radical addition to indole 264 and reduction of benzyl radical 272 led to the TMS + activated carbanion 273, which underwent diastereoselective [3,3] rearrangement and generated prenylated indoline product 267–270 with a high dr value (>20 : 1).…”