American Chemical Society
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Copper(I)-Catalyzed 1,3-Dipolar Cycloaddition of Ketonitrones to Dialkylcyanamides: A Step toward Sustainable Generation of 2,3-Dihydro-1,2,4-oxadiazoles

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posted on 2017-04-10, 15:50 authored by Anna A. Melekhova, Andrey S. Smirnov, Alexander S. Novikov, Taras L. Panikorovskii, Nadezhda A. Bokach, Vadim Yu. Kukushkin
CuI-catalyzed cycloaddition (CA) of the ketonitrones, Ph2CN+(R′)­O (R′ = Me, CH2Ph), to the disubstituted cyanamides, NCNR2 (R = Me2, Et2, (CH2)4, (CH2)5, (CH2)4O, C9H10, (CH2Ph)2, Ph­(Me)), gives the corresponding 5-amino-substituted 2,3-dihydro-1,2,4-oxadiazoles (15 examples) in good to moderate yields. The reaction proceeds under mild conditions (CH2Cl2, RT or 45 °C) and requires 10 mol % of [Cu­(NCMe)4]­(BF4) as the catalyst. The somewhat reduced yields are due to the individual properties of 2,3-dihydro-1,2,4-oxadiazoles, which easily undergo ring opening via NO bond splitting. Results of density functional theory calculations reveal that the CA of ketonitrones to CuI-bound cyanamides is a concerted process, and the copper-catalyzed reaction is controlled by the predominant contribution of the HOMOdipole–LUMOdipolarophile interaction (group I by Sustmann’s classification). The metal-involving process is much more asynchronous and profitable from both kinetic and thermodynamic viewpoints than the hypothetical metal-free reaction.