Manipulation of Spiroindolenine Intermediates for Enantioselective Synthesis of 3-(Indol-3-yl)-Pyrrolidines

By manipulating the reactivity of spiroindolenine species, a sequential Michael/retro-Mannich/Mannich reaction of omega-indol-3-yl alpha,beta-unsaturated ketones was developed. In the presence of 10 mol % of a chiral phosphoric acid as the catalyst, a series of 3-(indol-3-yl)-pyrrolidines were synthesized in high yields (up to 91 %) with excellent stereoselectivities (up to 92 % ee, >19:1 d.r.). The products obtained here undergo diverse functional-group transformations. The mechanistic proposal of this reaction is supported by DFT calculations.