Convenient Synthesis of Pyrazolo[4′,3′:5,6]pyrano[4,3-c][1,2]oxazoles via Intramolecular Nitrile Oxide Cycloaddition

A simple and efficient synthetic route to the novel 3a,4-dihydro-3H,7H- and 4H,7H-pyrazolo[4 ',3 ':5,6]pyrano[4,3-c][1,2]oxazole ring systems from 3-(prop-2-en-1-yloxy)- or 3-(prop-2-yn-1-yloxy)-1H-pyrazole-4-carbaldehyde oximes has been developed by employing the intramolecular nitrile oxide cycloaddition (INOC) reaction as the key step. The configuration of intermediate aldoximes was unambiguously determined using NOESY experimental data and comparison of the magnitudes of (1)J(CH) coupling constants of the iminyl moiety, which were greater by approximately 13 Hz for the predominant syn isomer. The structures of the obtained heterocyclic products were confirmed by detailed H-1, C-13 and N-15 NMR spectroscopic experiments and HRMS measurements.

Automated summary

A novel synthetic route to pyrazolo[4',3':5,6]pyrano[4,3-c][1,2]oxazole ring systems was developed using intramolecular nitrile oxide cycloaddition reaction. The configuration of intermediate aldoximes was determined using NOESY data and J(CH) coupling constants. The structures of the obtained heterocyclic products were confirmed using H-1, C-13, N-15 NMR spectroscopy and HRMS.