Nickel-Catalyzed Synthesis of Pyrazolo[3,4-c]pyridines via Alkyne Annulation

Significance

Reported is a reasonably efficient Ni-catalyzed synthesis of polysubstituted pyrazolo[3,4-c]pyridines by the annulation of alkynes with iodopyrazolocarboximines. The starting pyrazoles are readily prepared in two steps from protected 4-iodopyrazoles in 50-60% overall yield. Annulations using internal alkynes (R³ and R⁴ ∂ H) always proceed in higher yields but with lower regioselectivity (when R³ and R⁴ are different) than reactions using terminal alkynes. The tolerance of functional R¹ and R² substitutents was inadequately investigated. In one case, a Pd catalyst, PdCl₂(PhCN)₂, was successfully tested for the annulation.