(652g) Computational Search of Improved Homogeneous Catalysts for the Buchwald-Hartwig Amination Reaction

The formation of C–N bonds on arylic substrates is a process of pivotal importance for the production of pharmaceuticals, agrochemicals, and polymers. In this context, the Buchwald-Hartwig Amination (BHA) reaction is among the most studied chemistries for the conversion of aryl halides to aryl amines, catalyzed by Pd-based organometallic complexes [1–4].

In the recent past, we have developed fundamental and mechanistic understanding on the BHA reaction, by studying 37 different catalysts using bromobenzene and methylamine as substrates. In particular, by combining Density Functional Theory calculations with a descriptor-based approach based on the identification of scaling relations [5] and the construction of volcano activity plots, we have rationalized experimental activity trends of Pd centers coordinated by first, second, and third-generation phosphine ligands. Among the 37 catalysts, we have identified Me₄^tBuXPhos as the most active monophosphine ligand for amination of bromobenzene with methylamine [6].

By leveraging on our previous study, we have now engaged in high-throghput computational screening of catalytic materials for the BHA reaction, including more than 70 new candidates containing a wide range of electron-withdrawing groups. Furthermore, we have developed new inisghts on the transferability of scaling relations across different catalysts/substrates combinations for the BHA reaction.

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[4] A. S. Guram, R. A. Rennels, S. L. Buchwald, Angew. Chem. Int. Ed. Engl. 1995, 34, 1348–1350.

[5] M. Anand, B. Rohr, M. J. Statt, J. K. Nørskov, J. Phys. Chem. Lett. 2020, 11, 20, 8518–8526.

[6] M. Anand, J. K. Nørskov, ACS Catal. 2020, 10, 1, 336–345.