Catalytic Enantioselective Ynamide Additions to Isatins: Concise Access to Oxindole Alkaloids

The highly enantioselective addition of terminal ynamides to a variety of isatins, catalyzed by a bisoxazolidine copper complex under mild, base-free reaction conditions, is described. The reaction is broad in scope, scalable, applicable to unprotected isatins, and provides efficient access to 3-hydroxyoxindoles carrying a tetrasubstituted chiral center with excellent yields and enantioselectivities. Synthetically versatile, multifunctional 3-hydroxyindolinones are obtained by hydration, partial hydrogenation, or hydroxyacyloxylation of the ynamide moiety at room temperature and exhaustive hydrogenation followed by reductive detosylation and spontaneous cyclization affords cinchonamidine alkaloids.