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

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.