Lewis acid-catalyzed regiodivergent N-alkylation of indazoles with donor–acceptor cyclopropanes†

Abstract

N-Alkyl indazoles are highly important skeletons in the pharmaceutical field. Generally, N¹- and N²-alkyl indazoles exhibit distinct pharmaceutical and biological activities due to their differing molecular shapes and electrostatic distributions. Herein, we describe a regiodivergent N-alkylation of indazoles via the nucleophilic ring opening of D–A cyclopropanes by employing different Lewis acid catalysts. Under catalysis with Al(OTf)₃, kinetic controlled N²-alkyl indazoles were achieved, while Co(NTf₂)₂ facilitated the formation of N¹-alkyl indazoles. The methodology exhibited a broad substrate scope, affording the corresponding N¹- and N²-alkylation products selectively in high yields with good to excellent regioselectivities.