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

Abstract

Abstract 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 (RuCl 3 ⋅3 H 2 O) 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.