Carbene-catalyzed asymmetric Friedel–Crafts alkylation-annulation sequence and rapid synthesis of indole-fused polycyclic alkaloids

摘要

Organocatalyzed asymmetric Friedel–Craft reactions have enabled the rapid construction of chiral molecules with highly enantioselectivity enriching the toolbox of chemists for producing complex substances. Here, we report N-heterocyclic carbene-catalyzed asymmetric indole Friedel–Crafts alkylation-annulation with α,β-unsaturated acyl azolium as the key intermediate, affording a large variety of indole-fused polycyclic alkaloids with excellent diastereo- and enantioselectivities. The reaction mechanism is also investigated, and the reaction products can be easily converted to highly functionalized indole frameworks with different core structures. Indole-fused polycyclic alkaloids are present in numerous bioactive natural products. Here an enantioselective N-heterocyclic carbene-catalysed Friedel–Crafts alkylation/annulation cascade using acyl azolium salts as the electrophile provides access to these products with high stereoselectivity.