β- and Z-selective metal-free cyanation of ynamides: a direct approach to piperidines fused to arenes

Abstract

Metal-free β- and 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.