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 ω‐indol‐3‐yl α,β‐unsaturated ketones was developed. In the presence of 10 mol % of chiral phosphoric acid as the catalyst, a series of 3‐(indol‐3‐yl)‐pyrrolidines were synthesized in high yields with excellent stereoselectivities. The products undergo diverse functional‐group transformations and the mechanistic proposal is supported by DFT calculations.

Abstract

By manipulating the reactivity of spiroindolenine species, a sequential Michael/retro‐Mannich/Mannich reaction of ω‐indol‐3‐yl α,β‐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.

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