A Practical and Effective Ruthenium Trichloride‐Based Protocol for the Regio‐ and Stereoselective Catalytic Hydroamidation of Terminal Alkynes

A rational catalyst development based on mechanistic and spectroscopic investigations led to the discovery of a new protocol for catalytic hydroamidation reactions that draws on easily available ruthenium trichloride trihydrate (RuCl3⋅3 H2O) as the catalyst precursor instead of the previously employed, expensive bis(2‐methylallyl)(1,5‐cyclooctadiene)ruthenium(II). This practical and easy‐to‐use protocol dramatically improves the synthetic applicability of Ru‐catalyzed hydroamidations. The catalyst, generated in situ from ruthenium(III) chloride hydrate, tri‐n‐butylphosphine, 4‐(dimethylamino)pyridine and potassium carbonate, effectively promotes the addition of secondary amides, lactams and carbamates to terminal alkynes under formation of (E)‐anti‐Markovnikov enamides. The scope of the new protocol is demonstrated by the synthesis of 24 functionalized enamide derivatives, among them valuable intermediates for organic synthesis.