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

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 rutheniumA C H T U N G T R E N N U N G (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.

Z-Selective hydroamidation of terminal alkynes with secondary amides and imides catalyzed by a Ru/Yb-system

“…13 C NMR (CDCl 3 -d 1 , 101 MHz) d ¼ 166. 4, 132.5, 132.0, 123.2, 116.9, 31.3, 28.5, 22.6, 14. (13), 186 (77), 130 (24). IR (NaCl) 1663,1718,1764,1785,2858,2956, 3041 cm À1 .…”

“…101 MHz) d ¼ 174.5,137.2,129.7,126.9,124.8,111.8,47.9,30.1,18.6 ppm. MS (EI,70 eV), m/z (%) ¼ 187 (M þ , 100), 159 (11), 132 (52), 130 (52), 117 (26), 115 (24), 77 (20).…”

“…The scope of the initial protocol, in which ruthenium phosphines complexes in combination with auxiliary bases were employed as catalysts, included secondary amides, ureas, lactams, and oxazolidinones [23,24]. The stereoselectivity of the addition reaction was determined by the choice of ligands and bases.…”

Rhodium catalyzed one-step hydroamidation of cyclopentadiene and dicyclopentadiene

“…[16][17][18][19][20] The one-step-HAD reaction is a onepot synthesis of an alkene and an amine in the presence of carbon monoxide. [16][17][18][19][20] The one-step-HAD reaction is a onepot synthesis of an alkene and an amine in the presence of carbon monoxide.…”

Novel Four‐Component Approach for the Synthesis of Polyfunctionalized 1,4‐Dihydropyridines in Aqueous Media

“…The results are summarized in the Table. Results and Discussion. -The addition of nucleophiles across CC bonds has evolved to become a versatile tool for the synthesis of compounds with different functional groups [9]. Typically, the addition of amines to acetylenedicarboxylate (¼ but-2-ynedioate) derivatives has been extensively studied [10], and the DMADÀ primary-amine adducts are used as efficient starting materials for the synthesis of heterocyclic skeletons (DMAD ¼ dimethyl but-2-ynedioate) [11].…”