Atroposelective synthesis of N–N axially chiral pyrrolyl(aza)-quinolinone by de novo ring formation

Abstract

We herein report a chiral phosphoric acid-catalyzed Paal–Knorr reaction of N-amino(aza)quinolinones and 1,4-diketones for constructing N–N axially chiral pyrrolyl(aza)quinolinones with ‘6–5’-membered rings. The protocol proceeds smoothly under mild conditions, exhibiting excellent functional group compatibility and delivering a diverse set of pyrrolyl(aza)quinolinones in excellent yields with high atroposelectivities. Moreover, this strategy is applicable for the atroposelective synthesis of N–N axially chiral pyrrolyl-dihydroquinolinone/pyridinone and shows broad further synthetic transformations. Additionally, density functional theory studies unveiled that the key to control axially chiral N–N atropisomers is based on the second dehydroxylation process as the rate-determining step, not the first cyclization step. Therefore, this work not only offers a new family member of N–N atropisomers but also reveals the origin of the atroposelectivity.