Rational selection of co-catalysts for the deaminative hydrogenation of amides

• Published in: Chemical science (Cambridge) Vol. 11; no. 8; pp. 2225 - 223
• Main Authors: Artús Suàrez, Lluís, Jayarathne, Upul, Balcells, David, Bernskoetter, Wesley H, Hazari, Nilay, Jaraiz, Martín, Nova, Ainara
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 28.02.2020
• Subjects: Amides; Amines; Base metal; Catalysts; Chemical synthesis; Chemistry: 440; Crystallography; Hydrogenation; INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; Kjemi: 440; Matematikk og Naturvitenskap: 400; Mathematics and natural science: 400; VDP
• ISSN: 2041-6520; 2041-6539; 2041-6539
• DOI: 10.1039/c9sc03812d

The catalytic hydrogenation of amides is an atom economical method to synthesize amines. Previously, it was serendipitously discovered that the combination of a secondary amide co-catalyst with ( iPr PNP)Fe(H)(CO) ( iPr PNP = N[CH 2 CH 2 (P i Pr 2 )] 2 − ), results in a highly active base metal system for deaminative amide hydrogenation. Here, we use DFT to develop an improved co-catalyst for amide hydrogenation. Initially, we computationally evaluated the ability of a series of co-catalysts to accelerate the turnover-limiting proton transfer during C-N bond cleavage and poison the ( iPr PNP)Fe(H)(CO) catalyst through a side reaction. TBD (triazabicyclodecene) was identified as the leading co-catalyst. It was experimentally confirmed that when TBD is combined with ( iPr PNP)Fe(H)(CO) a remarkably active system for amide hydrogenation is generated. TBD also enhances the activity of other catalysts for amide hydrogenation and our results provide guidelines for the rational design of future co-catalysts. Theory and experiments were used to rationally design co-catalysts for the deaminative hydrogenation of amides. TBD was found to be the optimal catalyst, assisting the C-N bond cleavage while preventing the formation of adducts with the catalyst.