Abstract
Direct synthetic routes to amidines are desired, as they are widely present in many biologically active compounds and organometallic complexes. N-Acyl amidines in particular can be used as a starting material for the synthesis of heterocycles and have several other applications. Here, we describe a fast and practical copper-catalyzed three-component reaction of aryl acetylenes, amines, and easily accessible 1,4,2-dioxazol-5-ones to N-acyl amidines, generating CO2 as the only byproduct. Transformation of the dioxazolones on the Cu catalyst generates acyl nitrenes that rapidly insert into the copper acetylide Cu-C bond rather than undergoing an undesired Curtius rearrangement. For nonaromatic dioxazolones, [Cu(OAc)(Xantphos)] is a superior catalyst for this transformation, leading to full substrate conversion within 10 min. For the direct synthesis of N-benzoyl amidine derivatives from aromatic dioxazolones, [Cu(OAc)(Xantphos)] proved to be inactive, but moderate to good yields were obtained when using simple copper(I) iodide (CuI) as the catalyst. Mechanistic studies revealed the aerobic instability of one of the intermediates at low catalyst loadings, but the reaction could still be performed in air for most substrates when using catalyst loadings of 5 mol %. The herein reported procedure not only provides a new, practical, and direct route to N-acyl amidines but also represents a new type of C-N bond formation.
Original language | English |
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Pages (from-to) | 15240-15249 |
Number of pages | 10 |
Journal | Journal of the American Chemical Society |
Volume | 141 |
Issue number | 38 |
Early online date | 29 Aug 2019 |
DOIs | |
Publication status | Published - 25 Sept 2019 |
Funding
This research was supported by The Netherlands Organization for Scientific Research (NWO), the Holland Research School of Molecular Chemistry (HRSMC), and the UvA Research Priority Area “Sustainable Chemistry”. We would like to thank Lukas Wolzak, Eduard O. Bobylev, and Ed Zuidinga for the mass spectrometry measurements and Xavier Caumes for leading us to the [Cu(OAc)(Xantphos)] complex.
Funders | Funder number |
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Netherlands Organization for Scientific Research | |
UvA Research Priority Area | |
Nederlandse Organisatie voor Wetenschappelijk Onderzoek | |
Holland Research School of Molecular Chemistry |
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CCDC 1937520: Experimental Crystal Structure Determination
van Vliet, K. M. (Contributor), Polak, L. H. (Contributor), Siegler, M. A. (Contributor), van der Vlugt, J. I. (Contributor), Guerra, C. F. (Contributor) & de Bruin, B. (Contributor), Unknown Publisher, 25 Sept 2019
DOI: 10.5517/ccdc.csd.cc2314nz, http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccdc.csd.cc2314nz&sid=DataCite
Dataset / Software: Dataset