Synthesis of Imidazolidin-2-ones and Imidazol-2-ones via Base-Catalyzed Intramolecular Hydroamidation of Propargylic Ureas under Ambient Conditions

• Published in: Journal of organic chemistry Vol. 84; no. 6; pp. 3477 - 3490
• Main Authors: Casnati, Alessandra, Perrone, Antonio, Mazzeo, Paolo P, Bacchi, Alessia, Mancuso, Raffaella, Gabriele, Bartolo, Maggi, Raimondo, Maestri, Giovanni, Motti, Elena, Stirling, András, Ca’, Nicola Della
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 15-03-2019
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.9b00064

The first organo-catalyzed synthesis of imidazolidin-2-ones and imidazol-2-ones via intramolecular hydroamidation of propargylic ureas is reported. The phosphazene base BEMP turned out to be the most active organo-catalyst compared with guanidine and amidine bases. Excellent chemo- and regioselectivities to five-membered cyclic ureas have been achieved under ambient conditions, with a wide substrate scope and exceptionally short reaction times (down to 1 min). A base-mediated isomerization step to an allenamide intermediate is the most feasible reaction pathway to give imidazol-2-ones, as suggested by DFT studies.