Lewis Acid-Catalyzed Diastereoselective Domino Reaction of Ene-Ynamide with Trimethylsilyl Cyanide to Construct Spiroindolines

Abstract

The Zn­(OTf)2-catalyzed domino reaction of enamide-ynamides in the presence of trimethylsilyl cyanide as an external nucleophile to construct spirocyclic indolines was developed. This domino reaction involved cyclization of enamide to ynamide to generate 4′,5′-dihydrospiro­[indoline-3,3′-pyrrol]-1′-ium followed by cyanide addition to produce spiroindolopyrrolidines with good diastereoselectivity.

Efficient Synthesis of Medium‐sized Nitrogen Heterocycles by Brønsted Acid‐Catalyzed Cyclization of Ene‐ynamides

“…Recently, we have investigated an acid-promoted cyclization of eneynamides to synthesize multi-cyclic quinolines and spiroindolines toward the synthesis of marinoquinolines and aplidiopsamine A and formal synthesis of coerulescine. [13] As part of our ongoing work, we envisioned that cyclization of ene-ynamides could be extended to synthesis of medium-sized rings. As a working hypothesis for successful medium-ring construction, we expected that the use of a less reactive C=C double bond as a nucleophile would prevent intermolecular dimerization.…”