Visible-Light-Enabled Ir-Catalyzed Asymmetric Allylic Etherification and Dearomative Photocycloaddition

Area of Science:

• Organic Chemistry
• Photocatalysis
• Asymmetric Synthesis

Background:

• Conventional asymmetric allylic dearomatization typically occurs in the ground state.
• Indoles in the triplet state offer unique reactivity pathways for dearomatization reactions.

Purpose of the Study:

• To develop a novel relay catalytic system integrating visible-light-enabled iridium-catalyzed asymmetric allylic etherification and dearomative [2 + 2] photocycloaddition.
• To leverage the reactivity of triplet-state indoles for asymmetric dearomatization.
• To synthesize cyclobutane-fused indolines with high yields and selectivities.

Main Methods:

• Visible-light irradiation with blue LEDs.
• Iridium-catalyzed asymmetric allylic etherification.
• Dearomative [2 + 2] photocycloaddition.
• Mechanistic studies including control experiments and intermediate isolation.
• Kinetic analysis and "same excess" experiments.

Main Results:

• A diverse array of cyclobutane-fused indolines was synthesized.
• Achieved up to 92% yield with excellent diastereoselectivity (>20:1 dr) and enantioselectivity (>99% ee).
• Demonstrated *in situ* generation of HCl from CHCl3 irradiation, promoting the allylic substitution.
• Showcased acceleration of allylic substitution by photocycloaddition via consumption of the allyl ether intermediate.

Conclusions:

• The developed relay catalysis achieves a synergistic "1 + 1 > 2" effect.
• This strategy enables the synthesis of thermally disfavored cyclobutane-fused indolines.
• The system offers a powerful new approach for constructing complex indole derivatives.