Asymmetric Catalytic 1,2‐Azaarene Migration to α‐Azaaryl‐α‐Hydroxy Esters Enabled by a Tailored Ligand
Abstract
AbstractDespite their prevalence in bioactive molecules, the stereoselective construction of α‐azaaryl‐α‐hydroxycarboxylates remains a formidable challenge. Notably, although the benzilic ester rearrangement (BER) is an efficient approach to α‐hydroxycarboxylates, asymmetric catalytic BER remains poorly developed, largely due to poor stereorecognition of the vicinal diketone substituents by common chiral catalysts. In response to these issues, here we report a copper‐catalyzed asymmetric BER of azaarene‐derived 1,2‐diketones with simple alcohols to give diverse α‐azaaryl‐α‐hydroxy esters. It is proposed that the azaarene nitrogen and the adjacent carbonyl group chelate copper to form a five‐membered metallacycle, initiating the subsequent stereoselective 1,2‐nucleophilic addition step. Meanwhile, enantiocontrol over vicinal diketones was achieved by a tailored bisoxazoline (BOX) ligand with two rigid, long, and terminally bulky sidearms. This study overcomes the incompatibility between azaarenes and BOX ligands, and also unlocks asymmetric catalytic 1,2‐azaarene migrations.
Article Details
Authors (5)
Xing‐Zi Li
Shanghai Frontiers Science Center for Drug Target Identification and Delivery, National Key Laboratory of Innovative Immunotherapy and Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs School of Pharmaceutical Sciences Shanghai Jiao Tong University Shanghai 200240 China
Yue‐Hai Xu
Shanghai Frontiers Science Center for Drug Target Identification and Delivery, National Key Laboratory of Innovative Immunotherapy and Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs School of Pharmaceutical Sciences Shanghai Jiao Tong University Shanghai 200240 China
Fang‐Zhou Li
Shanghai Frontiers Science Center for Drug Target Identification and Delivery, National Key Laboratory of Innovative Immunotherapy and Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs School of Pharmaceutical Sciences Shanghai Jiao Tong University Shanghai 200240 China
Yu‐Ping He
Shanghai Frontiers Science Center for Drug Target Identification and Delivery, National Key Laboratory of Innovative Immunotherapy and Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs School of Pharmaceutical Sciences Shanghai Jiao Tong University Shanghai 200240 China
Hua Wu