Chemoselective cross-coupling of terminal propargylamines with (het)aroyl chlorides: synthesis of β-aminoacetylenic ketones bearing aromatic and heteroaromatic substituents

Pd/Cu‐Catalyzed Cross‐Coupling of Densely Substituted Propargylamines with Aromatic Acyl Chlorides Followed by the Treatment with a Base: Access to Dihydro‐3H‐Pyrrol‐3‐Ones

“…Indeed, as follows from Table 2, it proved to be the case. According to previous protocols for other acetylene/acyl chloride pairs [9,12] the cross‐coupling of propargylamines and acyl chlorides proceeded readily in the presence of PdCl 2 /Ph 3 P/CuI catalytic system (2:2:4 mol%, respectively) in toluene/Et 3 N solvent mixture (5:1 molar ratio), the latter also serving as HCl acceptor. The isolated yields of the target aminoacetylenic ketones 2 were 76–97%.…”

“…In view that all the above approaches to the assembly of 1,2‐dihydro‐3 H ‐pyrrol‐3‐ones represent at their finishing step an intramolecular cyclization of functionalized aminoketones, we assumed that for this purpose appear to be suitable α‐aminoacetylenic ketones 2 (Scheme 2). As our most recent sketchy trials show, such ketones can be derived from aryl(hetaryl)propargylamines 1 with terminal acetylenic moiety and aromatic(heteroaromatic) acyl chlorides [9] . The former are readily available through the base‐catalyzed addition of acetylenes to aryl(hetaryl)ketimines (KO t Bu/DMSO, 20–25 °C, 1 h) (Scheme 2A) [10]…”