Gold(I)-Catalyzed Alkynylation of N,O-Acetals: An Access to Alkynylated Saturated N-heterocycles

A synthetic route for the preparation of alkynylated saturated N-heterocycles via a sequential combination of a Shono oxidation and a gold(I)-catalyzed alkynylation reaction has been developed. The electrochemical Shono oxidation allowed an efficient access to a variety of N,O-acetals via a direct C-H bond functionalization of cyclic amines. The reaction conditions were amenable with functionalized pyrrolidine, tetrahydroisoquinoline and pyrrolidine-cyclopropyl fused bicyclic skeletons. The gold-catalyzed process allowed the introduction of aryl acetylene partners bearing electron-donating and moderate electron-withdrawing. The efficiency of the gold process is remarkable and could be scaled up to 5 mmol of N,O-acetal. Post-functionalization reactions were performed based on the reactivity of the alkyne, showing the broad interest of our methodology. Promising preliminary results on an asymmetric version were obtained (e.r. up to 84.5:15.5).

Automated summary

A synthetic route for alkynylated saturated N-heterocycles was developed via a sequential combination of Shono oxidation and gold(I)-catalyzed alkynylation reaction. The electrochemical Shono oxidation enabled efficient access to various N,O-acetals through direct C-H bond functionalization of cyclic amines. The gold-catalyzed process allowed the introduction of aryl acetylene partners with different electron properties. Promising initial results on asymmetric version were obtained.