Sustainable amidation through acceptorless dehydrogenative coupling by pincer-type catalysts: recent advances

Michael Montag, David Milstein

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


The amide functional group is ubiquitous in living organisms, and is of particular importance in bioactive compounds and pharmaceuticals. Because of the prevalence and significance of the amide bond, considerable efforts have been invested throughout the years in developing new synthetic methodologies for its formation. Nevertheless, amide synthesis still largely relies on variants of the traditional condensation of carboxylic acids and amines, mediated by stoichiometric coupling reagents. This poses a sustainability challenge, since such reactions suffer from unfavorable atom and step economies, involve harmful chemicals and produce chemical waste. Hence, establishing sustainable approaches to amide synthesis is of great importance. Over the last two decades, we have developed homogeneous catalytic reactions for sustainable synthetic transformations, primarily based on transition metal complexes of pincer ligands. A considerable portion of these efforts has been devoted to acceptorless dehydrogenative coupling, including that of alcohols and amines through ruthenium-catalyzed reactions. These latter processes generate amides without resorting to coupling reagents and typically produce no waste, with their only byproduct being H2 gas, which is itself a valuable resource. In the present review, we chronicle our progress in this area of research since 2014. This includes the use of water and ammonia as amidation reagents, expanding the scope of amidation substrates and target amides, achieving milder reaction conditions, development of amidation-based liquid organic hydrogen carrier systems, and introduction of manganese-based catalysts.

Original languageEnglish
Pages (from-to)109-124
Number of pages16
JournalPure and Applied Chemistry
Issue number2
StatePublished - 1 Feb 2023
Externally publishedYes


  • 2021 IUPAC-Zhejiang NHU International Award for Advancements in Green Chemistry Topic
  • acceptorless
  • alcohol
  • amide
  • amine
  • ammonia
  • catalysis
  • complex
  • coupling
  • dehydrogenation
  • epoxide
  • ester
  • homogeneous
  • hydrogen
  • manganese
  • pincer
  • ruthenium
  • sustainable synthesis
  • water


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