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

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.