A general catalytic β-C-H carbonylation of aliphatic amines to β-lactams
American Association for the Advancement of Science
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Willcox, D., Chappell, B., Hogg, K., Calleja, J., Smalley, A., & Gaunt, M. (2016). A general catalytic β-C-H carbonylation of aliphatic amines to β-lactams. Science, 354 (6314), 851-857. https://doi.org/10.1126/science.aaf9621
Methods for the synthesis and functionalization of amines are intrinsically important to a variety of chemical applications. We present a general carbon-hydrogen bond activation process that combines readily available aliphatic amines and the feedstock gas carbon monoxide to form synthetically versatile value-added amide products. The operationally straightforward palladium-catalyzed process exploits a distinct reaction pathway, wherein a sterically hindered carboxylate ligand orchestrates an amine attack on a palladium anhydride to transform aliphatic amines into β-lactams. The reaction is successful with a wide range of secondary amines and can be used as a late-stage functionalization tactic to deliver advanced, highly functionalized amine products of utility for pharmaceutical research and other areas.
We gratefully acknowledge funding from the European Research Council and the UK Engineering and Physical Sciences Research Council (EPSRC) (to D.W., K.F.H., A.P.S., and M.J.G.), the Herchel Smith Trust (to B.G.N.C.), the Marie Curie Foundation (to J.C.), and the Royal Society (Wolfson Merit Award to M.J.G.). Mass spectrometry data were acquired at the EPSRC UK National Mass Spectrometry Facility at Swansea University. Computational work was performed with the Darwin Supercomputer of the University of Cambridge High Performance Computing Service (http://www.hpc.cam.ac.uk/), provided by Dell, using Strategic Research Infrastructure Funding from the Higher Education Funding Council for England.
External DOI: https://doi.org/10.1126/science.aaf9621
This record's URL: https://www.repository.cam.ac.uk/handle/1810/261657