Base-mediated [3 + 2]-cycloannulation strategy for the synthesis of pyrazolo[1,5- a ]pyridine derivatives using ( E )-β-iodovinyl sulfones.

Pyrazolo[1,5- a ]pyridines continue to occupy a special place in medicinal chemistry, but the direct construction of 3-sulfonyl analogues remains unexplored. Under basic conditions, pyridinium- N -amine and the corresponding dipolar aminide played a vibrant role in [3 + 2]-cycloaddition using ( E )-β-iodovinyl sulfones. K 2 CO 3 -mediated tandem cycloannulative-desulfonylation of ( E )-β-iodovinyl sulfones with 1-aminopyridinium iodide is realized to access 2-substituted pyrazolo[1,5- a ]pyridines in good to high yields. An essential modification of the dipolar N -tosylpyridinium imide allows the first preparative synthesis of 3-sulfonyl-pyrazolo[1,5- a ]pyridines in moderate to high yields. Of note, the metal-free protocol features a broad substrate scope with good functional group tolerance and compatibility. The efficacy of the process was proved with gram-scale reactions, and a plausible mechanism is also presented based on concrete results.