Synthesis of pyrazole-fused polycyclic systems via intramolecular 1,3-dipolar cycloaddition reactions§

Abstract

Synthesis of a variety of pyrazole-fused systems starting from 4-iodopyrazolecarbaldehydes is described. The general strategy involves Suzuki coupling of 2-formyl aryl boronic acid with the 4-iodopyrazole derivatives generated from either Morita-Baylis-Hillman, Horner Wadsworth Emmons or Knoevenagel reactions followed by 1,3-dipolar cycloaddition reaction either by azomethine ylide or nitrile oxide. Interestingly, the cycloaddition reaction in substrates generated through Morita-Baylis-Hillman and Knoevenagel chemistries were diastereoselective for syn isomer. In contrast, the substrates prepared from Horner Wadsworth Emmons chemistry upon cycloaddition reactions afforded a mixture of syn and anti isomers in varying ratios