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 , Andy Whiting* 4 , and Tom Sheppard* 1 1) Department of Chemistry, University College London,UK; 2) Department of Chemistry, University of Manchester, UK; 3) Department of Chemistry, Imperial College London, UK; 4) Department of Chemistry, 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 water as the sole byproduct. Uncatalysed, this process has 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, and theoretical calculations, we have revealed key insights into boron catalysed amidation, 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 T. Y. Zhang. Green Chem. , 2007, 9 , 411–420 3. S. Arkhipenko, M. T. Sabatini, A. S. Batsanov, V. Karaluka, 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
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