Enantioselective synthesis of C–C and C–N axially chiral pyrazole-based heterobiaryls

Abstract

Axially chiral five-membered heteroaryls are prevalent in bioactive molecules. Their catalytic asymmetric synthesis remains challenging due to their relatively low rotational energy barriers. We developed a chiral nickel(II) complex-catalyzed asymmetric cycloaddition/oxidation sequential reaction of hydrazonoyl chlorides with α,β-unsaturated enones, which involves asymmetric [3 + 2] 1,3-dipolar cycloaddition of hydrazonoyl chlorides with α,β-unsaturated enones followed by oxidation to realize central-to-axial chirality transfer. A class of pyrazole-based heterobiaryls were prepared efficiently with high yields and good enantioselectivities. Based on the mechanistic study and control experiments, a possible mechanism was proposed to elucidate the reaction process and enantioinduction.