Asymmetric synthesis of 1H-pyrazolo[3,4-b]pyridine analogues catalyzed by chiral-at-metal Rh(iii) complexes†

Abstract

An efficient asymmetric Friedel–Crafts-type alkylation/cyclization of 5-aminopyrazoles with α,β-unsaturated 2-acyl imidazoles has been developed, affording corresponding pyrazolo[3,4-b]pyridine analogues in 81–98% yield with 85–99% enantioselectivity. Remarkably, this protocol exhibits extraordinary advantages in terms of reactivity and enantioselectivity, given the fact that chiral Rh(iii) complex at an amount as low as 0.05 mol% can promote the title reaction on the gram scale to afford the desired product, with excellent enantioselectivity (96% ee). Application of the methodology in the efficient synthesis of pyrazolo[3,4-b]pyridine via dehydrogenation is reported.