Asymmetric aminoarylation for the synthesis of trans-3-amino-4-aryltetrahydroquinolines: An access to aza-analogue of dihydrexidine

A proficient stereoselective aminoarylation reaction of N-cinnamylanilines, based on a two-step protocol of catalytic enantioselective aziridination and subsequent 6-endo-tet Friedel-Crafts cyclization, has been developed and demonstrated. A pair of chiral bis-oxazoline ligand and Cu(OTf)(2) offered an effective combination in the synthesis of trans-3-amino-4-aryltetrahydroquinolines with excellent diastereo- and enantioselectivity (dr: >99: 1 and ee up to 97%). In continuation, a trans-3-amino-4-aryltetrahydroquinoline, availed in one-pot stereoselective aminoarylation reaction, was extended toward a concise synthesis of aza-analogue of dihydrexdine, a potent and selective full dopamine-D1 agonist. (C) 2021 Elsevier Ltd. All rights reserved.

Automated summary

A proficient stereoselective aminoarylation reaction of N-cinnamylanilines was developed based on a two-step protocol involving catalytic enantioselective aziridination and subsequent 6-endo-tet Friedel-Crafts cyclization. The reaction showed excellent diastereo- and enantioselectivity in the synthesis of trans-3-amino-4-aryltetrahydroquinolines, with the potential for concise synthesis of bioactive compounds.