Ruthenium-Catalyzed Stereoselective anti-Markovnikov-Addition of Thioamides to Alkynes

Abstract

A catalyst system generated in situ from bis(2-methallyl)-cycloocta-1,5-diene-ruthenium(II) and a phosphine was found to efficiently catalyze the addition of thioamides to terminal alkynes with exclusive formation of the anti-Markovnikov thioenamide products. The stereoselectivity of the addition is usually high and controlled by the choice of the phosphine ligand, whereas the (E)-isomers are predominantly formed in the presence of tri(n-octyl)phosphine, the use of bis(dicyclohexylphosphino)methane preferentially leads to the formation of the (Z)-configured thioenamides.

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

“…Moreover, various N-nucleophiles could be added to 1-hexyne, including amides, lactams, bislactams, oxazolidinones, and even thioamide substrates that with (cod)RuA C H T U N G T R E N N U N G (met) 2 required a customized set of ligand and additive. [16] The yields and selectivities were usually high, but for acyclic amides do not quite reach those of the original protocol, which we attribute to the competition of remaining halide ions for coordination sites at the ruthenium giving rise to less active Ru species (Scheme 2, X = Cl). The protocol could easily be scaled up to gram quantities without any losses in yield or selectivity.…”

Computational study of the mechanism and selectivity of ruthenium-catalyzed hydroamidations of terminal alkynes

“…This was the first report of a transition metal-catalyzed N–H bond activation and addition of amides to alkynes. Based on this pioneering work, Gooßen et al have developed efficient ruthenium catalysts for the atom-economic addition of amides, carbamates, lactams, 29 imides 30 and thioamides 31 to terminal alkynes ( Scheme 1 and 2 ). Recent work in this area includes, e.g.…”

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

“…8,154.2,132.8,116.3,61.2,30.7,27.5,24.5,22.3,22.2,13.8 ppm. MS (EI,70 eV), m/z (%) ¼ 225 (MH þ , 100), 224 (10), 181 (11), 96 (13), 72 (15), 56 (26). IR (NaCl) 1662, 1719, 1777, 2871, 2930, 2956, 3044 cm À1 .…”

“…However, the scope and the Z-selectivity of this second protocol were only moderate. Improved catalyst systems allowed the extension of this reaction concept to imides [25], thioamides [26], and finally primary amides [27].…”