Stereoselective Desymmetrization of Cyclohexadienone-Tethered Enones: Efficient Access to Highly Strained Polycyclic Indoles

A highly regioselective and stereoselective cascade annulation of indoles with C2-symmetric enone tethered-cyclohexadienones provides rapid access to complex indole alkaloid-like scaffolds in high yields. Interestingly, a different reaction course was observed with 3-substituted indoles giving C-2/N annulation products with similar complexity via intramolecular aza-Michael addition. This desymmetrization approach is highly practical and allows atom-economical synthesis of natural product-like molecules containing several contiguous stereocenters with broad range of substrate scope and high functional-group tolerance. The synthetic utility of the products was demonstrated with various chemoselective, regioselective, and diastereoselective transformations on the highly strained polycyclic indoles to elaborate the value of this tandem reaction.