Carbene-catalyzed enantioselective annulation of dinucleophilic hydrazones and bromoenals for access to aryl-dihydropyridazinones and related drugs

• Main Authors: Mondal, Bivas, Maiti, Rakesh, Yang, Xing, Xu, Jun, Tian, Weiyi, Yan, Jia-Lei, Li, Xiangyang, Chi, Robin Yonggui
• Other Authors: School of Physical and Mathematical Sciences
• Format: Article
• Language: English
• Published: 2022
• Subjects: Science::Chemistry; Molecules; Reaction Intermediates
• Online Access: https://hdl.handle.net/10356/155061
• Institution: Nanyang Technological University

4,5-Dihydropyridazinones bearing an aryl substituent at the C6-position are important motifs in drug molecules. Herein, we developed an efficient protocol to access aryl-dihydropyridazinone molecules via carbene-catalyzed asymmetric annulation between dinucleophilic arylidene hydrazones and bromoenals. Key steps in this reaction include polarity-inversion of aryl aldehyde-derived hydrazones followed by chemo-selective reaction with enal-derived α,β-unsaturated acyl azolium intermediates. The aryl-dihydropyridazinone products accessed by our protocol can be readily transformed into drugs and bioactive molecules.