Indolization of N-Aryl Tertiary Amines with Diazoacetates by a Single Organophotocatalyst

Abstract

Diazoacetates are widely used to synthesize highly valuable indoles. Previous research has focused on using metal carbene reactivity or the innate nucleophilicity of the diazoacetates to create indoles through a traditional two-electron pathway. However, these strategies are constrained by the need for transition metals, oxidants, or substrate prefunctionalization. To overcome the limitations, we report herein an open-shell strategy that utilizes the radical reactivity of diazoacetates to synthesize indoles for the first time, especially for more valuable [a]-annulated indoles. Notably, this visible-light-driven transformation is enabled by a single organophotocatalyst, proceeding without metals ot additives. Preliminary mechanistic studies and density functional theory calculations disclose a relay visible-light photoredox catalytic process that probably involves several discrete photoredox catalytic cycles in a single operation with one organophotocatalyst.

Visible Light-Induced Reactions of Diazo Compounds and Their Precursors

“…Radical recombination between intermediate C and a transient α-ester radical D occurs, followed by reduction using a Hantzsch ester, delivering the desired γ-amino acid derivatives. Very recently, the groups of Hou and Li reported a photocatalytic approach for synthesis of various indole-fused tricyclic compounds 74.9 using diazo compounds 74.4 and N -phenylpiperidines 74.8 (Scheme C) . The mechanism of this protocol features the recombination between nucleophilic radical E and electrophilic radical D .…”

“…Very recently, the groups of Hou and Li reported a photocatalytic approach for synthesis of various indole-fused tricyclic compounds 74.9 using diazo compounds 74.4 and N-phenylpiperidines 74.8 (Scheme 74C). 167 The mechanism of this protocol features the recombination between nucleophilic radical E and electrophilic radical D.…”