Bifunctional Ligand-Assisted Catalytic Ketone α‑Alkenylation with Internal Alkynes: Controlled Synthesis of Enones and Mechanistic Studies

• Published in: Journal of the American Chemical Society 2015-12, Vol.137 (49), p.15518-15527
• Main Authors: Mo, Fanyang, Lim, Hee Nam, Dong, Guangbin
• Format: Article
• Language: English
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.5b10466

Here, we describe a detailed study of the rhodium­(I)-catalyzed, bifunctional ligand-assisted ketone α-C–H alkenylation using internal alkynes. Through controlling the reaction conditions, conjugated enamines, α,β- or β,γ-unsaturated ketones, can be selectively accessed. Both aromatic and aliphatic alkynes can be employed as coupling partners. The reaction conditions also tolerate a broad range of functional groups, including carboxylic esters, malonates, secondary amides, thioethers, and free alcohols. In addition, excellent E-selectivity was observed for the tetra-substituted alkene when forming the α,β-unsaturated ketone products. The mechanism of this transformation was explored through control experiments, kinetic monitoring, synthesizing the rhodium–hydride intermediates and their reactions with alkynes, deuterium-labeling experiments, and identification of the resting states of the catalyst.