Photocatalytic redox-neutral reaction of γ-indolyl α-keto esters

The direct gamma-C(sp(3))-H activation of saturated alpha-keto esters has long been an elusive transformation. We found that photoredox catalysis involving Ir-III in combination with DABCO as a dual hydrogen-bonding donor and organic base can lead to the transient generation of the multi-pi-electron gamma-enolyl radical from gamma-indolyl alpha-keto ester via enolization, oxidation and gamma-deprotonation. In the spin delocalized system, the gamma-enolyl radical can be easily reduced by Ir-II to form the gamma-enolyl anion and subsequently couple with a proton at the alpha-position of the ester. This mode of activation is suitable for the synthesis of various 4-indolyl substituted 2-hydroxy-3-enoic acid esters (in up to 90% yield and with up to Z/E >96 : 4) and is amenable for enantioselective catalysis.

Automated summary

Photoredox catalysis involving Ir-III in combination with DABCO as a dual hydrogen-bonding donor and organic base can enable the direct gamma-C(sp(3))-H activation of saturated alpha-keto esters, leading to the synthesis of various 4-indolyl substituted 2-hydroxy-3-enoic acid esters. This method offers high yields and high enantioselectivity.