Switchable Mono- and Dipropargylation of Amino Alcohols: A Unique Property of the Iodide Anion in Controlling Ring-Opening Alkynylation

The application of multicomponent reactions has been recognized as the most versatile strategy to achieve molecular diversity in organic synthesis. The reaction pathway and selectivity control of multicomponent reactions are associated with the effectiveness, the economy, and cleanliness of the process. Herein, a copper-catalyzed switchable process for the selective synthesis of N-propargyl oxazolidines and N,N-dipropargyl vicinal amino alcohols, by propargylation of amino alcohols, is disclosed. Mechanistic studies support a sequential process involving a copper-catalyzed annulation/A(3)-coupling of amino alcohol, and copper-catalyzed ring-opening alkynylation of the oxazolidine intermediate. Notably, the iodide anion would not affect the generation of oxazolidines, but it could shut down the cascade procedure of the alkynylation of these oxazolidines.

Automated summary

The application of multicomponent reactions in organic synthesis is a versatile strategy to achieve molecular diversity. In this study, a copper-catalyzed process for the selective synthesis of N-propargyl oxazolidines and N,N-dipropargyl vicinal amino alcohols was disclosed. The mechanism involves a sequential process of copper-catalyzed annulation/A(3)-coupling and copper-catalyzed ring-opening alkynylation.