Rapid Access to an Enantioenriched Spiro Bisindole Directly from Indole and Acetone

Disclosed here is a "one-pot self-assembly" strategy for the enantioselective synthesis of a spiro bisindole molecule directly from indole and acetone. This convenient synthesis contrasts drastically to the typical long sequence required for other privileged C₂-symmetric spirocycles. The use of an alcohol additive in cooperation with chiral phosphoric acid (CPA) catalysis proved crucial to the good efficiency and enantioselectivity. The favorable interaction between the additive and CPA was confirmed by nuclear magnetic resonance (NMR) and density functional theory (DFT) studies. The obtained enantiopure C₂-symmetric bisindole was demonstrated as a useful backbone of chiral catalysts/ligands.