A General and Highly Selective Palladium‐Catalyzed Hydroamidation of 1,3‐Diynes
Jiawang Liu, Carolin Schneider, Ji Yang, Zhihong Wei, Haijun Jiao, Robert Franke, Ralf Jackstell, Matthias Beller
Abstract
A chemo-, regio-, and stereoselective mono-hydroamidation of (un)symmetrical 1,3-diynes is described. Key for the success of this novel transformation is the utilization of an advanced palladium catalyst system with the specific ligand Neolephos. The synthetic value of this general approach to synthetically useful α-alkynyl-α, β-unsaturated amides is showcased by diversification of several structurally complex molecules and marketed drugs. Control experiments and density-functional theory (M06L-SMD) computations also suggest the crucial role of the substrate in controlling the regioselectivity of unsymmetrical 1,3-diynes.
Topics & Concepts
RegioselectivityPalladiumCatalysisStereoselectivityCombinatorial chemistryLigand (biochemistry)ChemistrySubstrate (aquarium)StereochemistryOrganic chemistryBiologyReceptorBiochemistryEcologyCatalytic C–H Functionalization MethodsChemical Synthesis and AnalysisAsymmetric Hydrogenation and Catalysis