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

ABSTRACT: 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.

SUBMITTER: Melekhova AA 

PROVIDER: S-EPMC6641119 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature