β-and Z-Selective Metal-Free Cyanation of Ynamides: A Direct Approach to Piperidines Fused to Arenes

Abstract

Metal-free βand Z-selective hydrocyanation of terminal ynamides using TMSCN and TBAF is described. The transformation proceeds with excellent regio-and stereoselectivity, delivering exclusively Z-configured tertiary enamides. Treatment with TMSOTf promotes clean Z to E isomerization. Simultaneous activation of the nitrile moiety by TMSOTf in the presence of an internal nucleophile induces intramolecular cyclization, yielding piperidine frameworks. The reaction accommodates a range of nucleophiles, enabling the synthesis of structurally diverse and previously inaccessible heterocyclic scaffolds.