Chiral Brønsted acid-catalyzed dynamic kinetic resolution of atropisomeric ortho-formyl naphthamides

• DOI: 10.1039/d0cc02380a
• Publication Date: 2020-05-19T11:38:52Z
• Authors: Zeng Gao; Jinlong Qian; Huameng Yang; Xiao-Chun Hang; Jinlong Zhang; Gaoxi Jiang
• Keywords: Atropisomer; Stereocenter; Kinetic resolution; Epimer; Axial Chirality; Chirality; Amide; Brønsted–Lowry acid–base theory

Despite the widespread use of naphthamide atropisomers in biologically active compounds and asymmetric catalysis, few catalytic methods have succeeded enantioselective synthesis these compounds. Herein, a chiral Brønsted acid (CBA) catalysis strategy was developed for readily scalable dynamic kinetic resolution challenging ortho-formyl naphthamides with pyrrolylanilines. The axis atropisomeric amide stereogenic center were simultaneously established new family potential pyrrolopyrazine high enantio- diastereoselectivities (up to >20 : 1 d.r. 98 2 e.r.). Epimerization experiments its derivatives reveal that N-substitution nearby could affect configurational stability axially aromatic amides. These results might be useful construction other kinds novel molecules low rotational barrier.