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Chiral Phosphoric Acid Catalyzed Kinetic Resolution of 2‐Amido Benzyl Alcohols: Asymmetric Synthesis of 4 H ‐3,1‐Benzoxazines
Author(s) -
Rajkumar Subramani,
Tang Mengyao,
Yang Xiaoyu
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201913896
Subject(s) - kinetic resolution , chemistry , catalysis , intramolecular force , amide , electrophile , phosphoric acid , combinatorial chemistry , organic chemistry , enantioselective synthesis
An efficient method for the asymmetric synthesis of 4 H ‐3,1‐benzoxazines was developed by kinetic resolution of 2‐amido benzyl alcohols using chiral phosphoric acid catalyzed intramolecular cyclizations. A broad range of benzyl alcohols (both secondary and tertiary alcohols) were kinetically resolved with high selectivities, with an s factor of up to 94. Mechanistic studies were performed to elucidate the mechanism of these reactions, wherein the amide moieties reacted as the electrophiles. Gram‐scale reaction and facile transformations of the chiral products demonstrate the potential of this method in asymmetric synthesis of biologically active chiral heterocycles.