Copper-Catalyzed Hydroamination: Enantioselective Addition of Pyrazoles to Cyclopropenes

J Am Chem Soc. 2023 Jul 12;145(27):14573-14580. doi: 10.1021/jacs.3c02971. Epub 2023 Jun 30.

Abstract

Chiral N-cyclopropyl pyrazoles and structurally related heterocycles are prepared using an earth-abundant copper catalyst under mild reaction conditions with high regio-, diastereo-, and enantiocontrol. The observed N2:N1 regioselectivity favors the more hindered nitrogen of the pyrazole. Experimental and DFT studies support a unique mechanism that features a five-centered aminocupration.