Regioselective and Enantioselective Synthesis of ß-Indolyl Cyclopentenamides by Chiral Anion Catalysis.

The regioselective and enantioselective synthesis of ß-indolyl cyclopentenamides, a versatile chiral building block, by asymmetric addition of indoles to α,ß-unsaturated iminium intermediates has been achieved through chiral anion catalysis. Key to the success of this methodology is the generation of a chiral anion-paired ketone-type α,ß-unsaturated iminium intermediate from α-hydroxy enamides. Preliminary mechanistic studies and DFT calculations are consistent with a mechanism involving multiple, concurrent pathways for isomerization of the initially formed azaallylcation into the key α,ß-unsaturated iminium intermediate, all mediated by the phosphoric acid catalyst.