Carbene-catalyzed enantioselective annulation of dinucleophilic hydrazones and bromoenals for access to aryl-dihydropyridazinones and related drugs |
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| Authors: | Bivas Mondal Rakesh Maiti Xing Yang Jun Xu Weiyi Tian Jia-Lei Yan Xiangyang Li Yonggui Robin Chi |
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| Affiliation: | State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Huaxi District, Guiyang 550025 China.; Guizhou University of Traditional Chinese Medicine, Guiyang 550025 China.; Division of Chemistry & Mathematical Science, School of Physical & Mathematical Sciences, Nanyang Technological University, Singapore 637371 Singapore, |
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| Abstract: | 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.Polarity inversion of arylidene hydrazones to react with bromoenals via carbene organic catalysis is disclosed. The reaction enantioselectively affords 6-aryl-4,5-dihydropyridazinones and related drugs with proven commercial applications. |
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