The ubiquity of sulfur-containing molecules in biologically active natural products and pharmaceuticals has long attracted synthetic chemists to develop efficient strategies towards their synthesis. The strategy of direct α-C(sp 3 )À H modification of sulfides provides a streamlining access to complex sulfur-containing molecules. Herein, we report a photoinduced chemo-, site-and stereoselective α-C(sp 3 )À H functionalization of sulfides using isatins as the photoredox reagent and coupling partner catalyzed by a chiral gallium(III)-N,N'-dioxide complex. The reaction proceeds through a verified single-electron transfer (SET) mechanism with high efficiency, excellent functional group tolerance, as well as a broad substrate scope. Importantly, this crosscoupling protocol is highly selective for the direct latestage functionalization of methionine-related peptides, regardless of the inherent structural similarity and complexity of diverse residues.
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.
The ubiquity of sulfur‐containing molecules in biologically active natural products and pharmaceuticals has long attracted synthetic chemists to develop efficient strategies towards their synthesis. The strategy of direct α‐C(sp3)−H modification of sulfides provides a streamlining access to complex sulfur‐containing molecules. Herein, we report a photoinduced chemo‐, site‐ and stereoselective α‐C(sp3)−H functionalization of sulfides using isatins as the photoredox reagent and coupling partner catalyzed by a chiral gallium(III)‐N,N′‐dioxide complex. The reaction proceeds through a verified single‐electron transfer (SET) mechanism with high efficiency, excellent functional group tolerance, as well as a broad substrate scope. Importantly, this cross‐coupling protocol is highly selective for the direct late‐stage functionalization of methionine‐related peptides, regardless of the inherent structural similarity and complexity of diverse residues.
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