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

Lluís Artús Suàrez; Upul Jayarathne; David Balcells; Wesley H Bernskoetter; Nilay Hazari; Martín Jaraiz; Ainara Nova

doi:10.1039/c9sc03812d

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

Chem Sci. 2020 Jan 20;11(8):2225-2230. doi: 10.1039/c9sc03812d. eCollection 2020 Feb 28.

Authors

Lluís Artús Suàrez¹, Upul Jayarathne², David Balcells¹, Wesley H Bernskoetter², Nilay Hazari³, Martín Jaraiz^{4

5}, Ainara Nova^{1

6}

Affiliations

¹ Hylleraas Centre for Quantum Molecular Sciences , Department of Chemistry , University of Oslo , P. O. Box 1033, Blindern , N-0315 Oslo , Norway . Email: ainara.nova@kjemi.uio.no.
² Department of Chemistry , University of Missouri , Columbia , Missouri 65211 , USA.
³ Department of Chemistry , Yale University , P. O. Box 208107 , New Haven , Connecticut 06520 , USA.
⁴ Department of Electronics , ETSIT , University of Valladolid , Paseo Belén 15 , 47011 Valladolid , Spain.
⁵ IU CINQUIMA , University of Valladolid , Paseo de Belén 7 , 47011 Valladolid , Spain.
⁶ Department of Chemistry , UiT-The Arctic University of Norway , N-9037 Tromsø , Norway.

Abstract

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 (^iPrPNP)Fe(H)(CO) (^iPrPNP = N[CH₂CH₂(PⁱPr₂)]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 (^iPrPNP)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 (^iPrPNP)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.