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 (RUCl3-3H(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.