Lukas J. Goossen

Mechanistic Investigation of the Ru-Catalyzed Hydroamidation of Terminal Alkynes

The ruthenium-catalyzed hydroamidation of terminal alkynes has evolved to become a broadly applicable tool for the synthesis of enamides and enimides. Depending on the catalyst system employed, the reaction leads chemo-, regio-, and stereoselectively to a single diastereoisomer. Herein, we present a comprehensive mechanistic study of the ruthenium-catalyzed hydroamidation of terminal alkynes, which includes deuterium-labeling, in situ IR, in situ NMR, and in situ ESI-MS experiments complemented by computational studies. The results support the involvement of ruthenium-hydride and ruthenium-vinylidene species as the key intermediates. They are best explained by a reaction pathway that consists of an oxidative addition of the amide, followed by insertion of a π-coordinated alkyne into a ruthenium-hydride bond, rearrangement to a vinylidene species, nucleophilic attack of the amide, and finally reductive elimination of the product.

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

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.

Doubly Regioselective C-H Hydroarylation of Unsymmetrical Alkynes Using Carboxylates as Deciduous Directing Groups

A catalyst system composed of [(C6Me6)RuCl2]2, potassium carbonate/guanidine carbonate, and mesitoic acid efficiently promotes the doubly regioselective C-H hydroarylation of unsymmetrical alkynes. The process involves carboxylate-directed ortho-C-H bond activation followed by regioselective addition to the alkyne C-C triple bond with concerted decarboxylation. This action of the carboxylate as a deciduous directing group ensures exclusive monovinylation with high selectivity for the (E)-1,2-diarylalkene.