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

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.