Metal-Catalyzed Cascade Reactions between Alkynoic Acids and Dinucleophiles: A Review

Abstract

Cascade reactions provide a straightforward access to many valuable compounds and reduce considerably the number of steps of a synthetic sequence. Among the domino and multicomponent processes that involve alkynes, the cascade reaction between alkynoic acids and C-, N-, O- and S-aminonucleophiles stands out as a particularly powerful tool for the one-pot construction of libraries of nitrogen-containing heterocyclic compounds with scaffold diversity and molecular complexity. This reaction, based on an initial metal-catalyzed cycloisomerization that generates an alkylidene lactone intermediate, was originally catalyzed by gold(I) catalysts, along with silver salts or Brönsted acid additives, but other alternative metal catalysts have emerged in the last decade as well as different reaction media. This review examines the existing literature on the topic of metal-catalyzed cascade reactions of acetylenic acids and dinucleophiles and discusses aspects concerning substrate/catalyst ratio for every catalyst system, nature of the aminonucleophile involved and substrate scope. In addition, alternative solvents are also considered, and an insight into the pathway of the reaction and possible intermediates is also provided.

Keywords

• cascade reactions
• domino processes
• metal catalysts
• cycloisomerization