Catalyst-Free Domino Reaction of Ethyl 4-Hydroxyalkyl-2-ynoate with N-Heteroarylmethyl-N-2,2-difluoroethan-1-amine

The catalyst-free domino reaction of ethyl 4-hydroxyalkyl-2-ynoate and N-heteroaryl-methyl-N-2,2-difluoroethan-1-amine was developed, and used to synthesize 4-(N-(2,2-difluoroethyl)(N-heteroarylmethyl)amino)-5,5-disubstitutedfuran-2(5H)-one in methanol under the reflux condition with yields of 39%similar to 83%. Their structures were characterized by H-1 NMR, C-13 NMR, and HR-ESI-MS data, further confirmed by the X-ray crystal diffraction of 3-chloro-4-((N-2,2-difluoroethyl)(N-pyrimidin-5-ylmethyl)amino)-5,5-spiro(4-methoxycyclohexyl)furan-2(5H)-one (8). The bioassay results showed that 4-((N-2,2-difluoroethyl)(N-6-chloropyridin-3-ylmethyl)amino)-5,5-dimethy lfuran-2(5H)-one (3a) and 4-((N-2,2-difluoroethyl)(N-6-fluoropyridin-3-ylmethyl)-amino)-5,5-dimethylfuran-2(5H)-one (3c) exhibit 100% mortality against Myzus persicae at the concentration of 600 mu g.mL(-1), respectively.