Enantioselective Synthesis of Indole-Fused Bicyclo[3.2.1]octanes via Palladium(II)-Catalyzed Cascade Reaction

Indole-fused bicyclo[3.2.1]octanes are highly important structural units in natural products and biologically active compounds. However, there has been limited success in the enantioselective synthesis of these skeletons due to the complexity of the structure and the control of the enantioselectivity. Herein an enantioselective construction of indole-fused bicyclo[3.2.1]octanes bearing an all-carbon quaternary bridgehead stereocenter was developed via an aminopalladition-triggered Heck-type reaction. The protocol features mild conditions and good tolerance for a wide range of functional groups. The transformation can also be scaled up to demonstrate its practicability. The mechanistic studies reveal that the formation of an intermediate indol-3-yl palladium species via C-H activation should be ruled out.

Automated summary

This paper presents an enantioselective construction method for indole-fused bicyclo[3.2.1]octanes, utilizing a Heck-type reaction triggered by aminopalladition to achieve construction of an all-carbon quaternary bridgehead stereocenter, with mild conditions and good tolerance for various functional groups. The method can be scaled up to demonstrate practicality.