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

Abstract

A simple and efficient synthetic route to the novel 3a,4-dihydro-3<i>H</i>,7<i>H</i>- and 4<i>H</i>,7<i>H</i>-pyrazolo[4',3':5,6]pyrano[4,3-<i>c</i>][1,2]oxazole ring systems from 3-(prop-2-en-1-yloxy)- or 3-(prop-2-yn-1-yloxy)-1<i>H</i>-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<i>J</i>_CH coupling constants of the iminyl moiety, which were greater by approximately 13 Hz for the predominant <i>syn</i> isomer. The structures of the obtained heterocyclic products were confirmed by detailed ¹H, ¹³C and ¹⁵N NMR spectroscopic experiments and HRMS measurements.