Catalytic Asymmetric Synthesis of 1,2-Fused Tricyclic Indoles Containing an Eight-Membered Biaryl Bridge

We disclose herein a diastereo- and enantioselective synthesis of tricyclic indoles containing an eight-membered-ring-bridged biaryl architecture from 2-(2-aminoaryl)indoles and β,γ-unsaturated α-ketoesters. This Friedel-Crafts alkylation/dehydration process was efficiently catalyzed by an In(OTf)₃-pybox complex to give the products featuring both central and axial chirality in generally high yields and stereoselectivities. A scale-up reaction and derivatization of the representative products were performed to study the synthetic potential of this transformation.