Boron mediated direct amidation reactions – mechanistic insights and catalyst development Richard Procter 1 , Carla Alamillo Ferrer 2 , Alexandre Dumon 3 , Jordi Bures 2 , Henry Rzepa 3* , Andrew Whiting 4 , Tom Sheppard 1 1 University College London, UK, 2 University of Manchester, UK, 3 Imperial College London, UK, 4 Durham University, UK
Amide bonds are found throughout nature and industry, from proteins to pharmaceuticals to plastics. Their ubiquity is reflected by the many well-established methodologies available for amide synthesis, and though these are considered generally effective, they typically require stoichiometric activating agents which are both hazardous and wasteful 1 . As such, pharmaceutical manufacturers have recognised ‘amide bond formation avoiding poor atom economy reagents’ as a key challenge for green chemical research 2 . Conceptually the simplest, and most efficient, amide synthesis is the direct coupling of an acid and an amine with environmentally benign water as the sole byproduct. Uncatalysed, this process has very limited scope and requires high temperatures. In recent years however, research efforts have revealed many catalysts capable of enabling this reaction, with boron based catalysts in particular showing good activity, though their mechanism is not yet fully understood 3,4 . This poster will present novel borate catalysts capable of catalysing direct amidation with enhanced efficiency and greater substrate tolerance than previously disclosed. Through a combination of kinetic investigation, heteronuclear NMR studies, reactivity of stoichiometric boron compounds, and theoretical calculations, we have revealed key insights into boron catalysed amidation – including the similarities and differences between related classes of catalyst, which will enable the rational design of the next generation of amidation catalysts. References 1. E. Valeur and M. Bradley, Chem. Soc. Rev. , 2009, 38 , 606-631 2. D. J. C. Constable, P. J. Dunn, J. D. Hayler, G. R. Humphrey, J. L. Leazer Jr, R. J. Linderman, K. Lorenz, J. Manley, B. A. Pearlman, A. Wells, A. Zaks, and T. Y. Zhang. Green Chem., 2007, 9 , 411–420 3. S. Arkhipenko, M. T. Sabatini, A. S. Batsanov, V. Karalua, T. D. Sheppard, H. S. Rzepa, and A Whiting, Chem. Sci. , 2018, 9 , 1058-1072 4. K. Wang, Y. Lu, and K. Ishihara, Chem. Commun. , 2018, 54 , 5410-5413
P92
© The Author(s), 2022
Made with FlippingBook Learn more on our blog