A highly efficient, two-step, one-pot synthetic strategy for amides and peptides was developed by employing ynamides as novel coupling reagents under extremely mild reaction conditions. The ynamides not only are effective for simple amide and dipeptide synthesis but can also be used for peptide segment condensation. Importantly, no racemization was detected during the activation of chiral carboxylic acids. Excellent amidation selectivity toward amino groups in the presence of -OH, -SH, -CONH, ArNH, and the NH of indole was observed, making the protection of these functional groups unnecessary in amide and peptide synthesis.

While gold‐mediated synergistic catalytic processes involving transmetalations with other metals are well understood, AuI/AuIII cycles in these reactions are rarely reported. Herein a gold‐catalyzed direct alkynylation of cyclopropenes is enabled by two operating catalytic cycles, an oxidative catalytic cycle involving an alkynyl AuIII complex formed by oxidative addition and one involving a silver‐mediated C−H activation.

The development of new methodologies enabling a facile access to valuable heterocyclic frameworks still is an important subject of research. In this context, we describe a dual catalytic cycle merging C−H alkynylation of phenols and oxy‐alkynylation of the newly introduced triple bond by using a unique redox property and the carbophilic π acidity of gold. Mechanistic studies support the participation of a bimetallic gold–silver species. The one‐pot protocol offers a direct, simple, and regio‐specific approach to 3‐alkynyl benzofurans from readily available phenols. A broad range of substrates, including heterocycles, is transferred with excellent functional group tolerance. Thus, this methodology can be used for the late‐stage incorporation of benzofurans.

Ynamides, a class of novel coupling reagents for peptide synthesis, facilitated peptide bond formation in a one-pot, two-step manner with α-acyloxyenamide active esters of amino acids as stable intermediates. Ynamide-mediated peptide synthesis proceeded by a reaction mechanism that is completely different from that of conventional coupling reagents and exhibited superiority in addressing the issue of racemization/ epimerization during peptide bond formation. Herein, we present a systematic mechanistic analysis, including kinetics and Brønsted-type structure-reactivity studies and density functional theory calculations, providing unprecedented mechanistic insight into ynamide-mediated peptide bond formation. Based on these mechanistic studies, significant improvements were made, and the applicability of ynamide-mediated peptide bond formation was successfully expanded to peptide fragment condensation, head-to-tail cyclization and solid-phase peptide synthesis.