Bipyridine-N,N′-dioxides Catalysts: Design, Synthesis, and Application in Asymmetric Synthesis of 1H-Pyrazolo[3,4-b]pyridine Analogues

Abstract

A novel type of highly efficient chiral C2-symmetric bipyridine-N,N′-dioxides ligand application in catalyzing Michael addition/Cyclization of 5-aminopyrazoles with α,β-unsaturated 2acyl imidazoles has been developed, affording the corresponding adducts in 85−97% yield with up to 99% enantioselectivity under mild conditions with a lower catalyst loading and broad scope. Remarkably, this protocol exhibits advantages in terms of reactivity and enantioselectivity, giving the fact that as low as 2.2 mol % of L1 and 2.0 mol % of Ni(OTf) 2 can promote the title reaction on gram scale to afford the desired product with excellent enantioselectivity.

Switchable Chemoselectivity in [3 + 3] Annulation of β,γ-Unsaturated α-Ketoesters and 1H-Pyrazol-5-amines by Cooperative Acid Catalysis with NiII and InI

“…1 H- Pyrazolo[3,4- b ]pyridine and dihydro-1 H -pyrazolo[3,4- b ]pyridine derivatives are privileged structural motifs, occurring frequently in numerous natural products, pharmaceuticals, and biologically active molecules (Figure ). − Therefore, numerous efforts have been devoted to developing efficient catalysts for the selective addition of α,β-unsaturated carbonyls with 1 H- pyrazol-5-amines. − Although many efforts have focused on the α,β-unsaturated carbonyls in formal [3 + 3] cycloaddition with enamines, − the exploitation of β,γ-unsaturated α-ketoesters remains less studied. − This is speculatively attributed to chemoselectivity issues arising from the differentiation of 1,2- and 1,4-addition pathways. In 2010, we first developed asymmetric binary-acid catalysis, which resulted in a synergistic effect for catalysis in regio-, diastereo-, and enantiodivergent , reactions.…”