Mechanistic Insights into Atom-Economical Bromoalkynylation of Ynamides: 1,3-Alkynyl Migration Explored through ¹³ C Kinetic Isotope Effects, X-ray Photoelectron Spectroscopy, and Density Functional Theory Analysis

Difunctionalization of ynamides, whether through an intermolecular approach or in an atom-economical manner, continues to pose a significant challenge. This work presents a simpler method for such unprecedented functionalization through highly regio- and stereoselective bromoalkynylation. The developed strategy, which requires a Pd(II) catalyst and no additive, has a broad scope and high functional-group tolerance and provided access to 50 value-added β-bromo ynenamides. In addition to late-stage functionalization, the synthetic potential of this method was demonstrated through rapid access to previously challenging π-skeletons. A unique 1,3-alkynyl migration, which was enabled by Pd(IV)-bound keteniminium species, offers a platform for the development of atom-economical reactions. Experimental evidence, such as from Hammett plot analysis, X-ray photoelectron spectroscopy studies, and 13C kinetic isotope effect measurements, supported by density functional theory computations enabled a comprehensive understanding of the mechanism.