5-Chloropyrazole-4-carbaldehydes as synthons for intramolecular 1,3-dipolar cycloadditions

Abstract

A general method is described to transform the readily available title compounds into tri- and tetra-cyclic heterocycles, first by substituting the chlorine atom by an unsaturated thiolate or alkoxide, and then by modifying the aldehyde function into a 1,3-dipole. As 1,3-dipoles, nitrile oxide, nitrone, nitrile imine, azomethine ylide and azomethine imine groups were generated from the 5-allylsulfanyl-4-formylpyrazole 7, which resulted in Intramolecular cycloaddition and formation of the heterocycles shown in Scheme 2. The other pyrazoles 22, 23, 26, 30 and 33 were converted via intramolecular nitrile oxide cycloaddition (INOC) into fused dihydroisoxazoles. A limitation to the method is the Claisen rearrangement which occurs when the allyl ether 26 or the prop-2-ynyl ether 30 is used.