Regiodivergent synthesis of aza-quaternary carbon derivatives from pyrazolinone ketimines and 1,2-dihydroquinolines

Abstract

Aza-quaternary carbon centers are present in numerous bioactive natural products, pharmaceutical drugs and alkaloids. However, the divergent construction of the aza-quaternary carbon motif is extremely challenging and remains underdeveloped. The potential electrophilicity at the C-4 position of pyrazolone provides alternative access to a variety of multifunctional pyrazolone derivatives. Herein, we disclose regiodivergent routes to construct aza-quaternary carbon frameworks from pyrazolinone ketimines and 1,2-dihydroquinolines. This method allows for the divergent synthesis of a variety of valuable pyrazolone derivatives bearing an aza-quaternary carbon center via 1,2-addition and aza-Friedel–Crafts pathways respectively, providing high regioselectivity, good to high yields and gram-scale capacity. Moreover, a plausible mechanism for the regioselectivity of this reaction is proposed.