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

[Image: see text] Cu(I)-catalyzed cycloaddition (CA) of the ketonitrones, Ph(2)C=N(+)(R′)O(–) (R′ = Me, CH(2)Ph), to the disubstituted cyanamides, NCNR(2) (R = Me(2), Et(2), (CH(2))(4), (CH(2))(5), (CH(2))(4)O, C(9)H(10), (CH(2)Ph)(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 (CH(2)Cl(2), RT or 45 °C) and requires 10 mol % of [Cu(NCMe)(4)](BF(4)) 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 Cu(I)-bound cyanamides is a concerted process, and the copper-catalyzed reaction is controlled by the predominant contribution of the HOMO(dipole)–LUMO(dipolarophile) 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.