Carbene-catalyzed enantioselective annulation of dinucleophilic hydrazones and bromoenals for access to aryl-dihydropyridazinones and related drugs
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 bromoena...
| Main Authors: | , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2022
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| Online Access: | https://hdl.handle.net/10356/155061 |
| _version_ | 1811684366508621824 |
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| author | Mondal, Bivas Maiti, Rakesh Yang, Xing Xu, Jun Tian, Weiyi Yan, Jia-Lei Li, Xiangyang Chi, Robin Yonggui |
| author2 | School of Physical and Mathematical Sciences |
| author_facet | School of Physical and Mathematical Sciences Mondal, Bivas Maiti, Rakesh Yang, Xing Xu, Jun Tian, Weiyi Yan, Jia-Lei Li, Xiangyang Chi, Robin Yonggui |
| author_sort | Mondal, Bivas |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T04:27:29Z |
| format | Journal Article |
| id | ntu-10356/155061 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T04:27:29Z |
| publishDate | 2022 |
| record_format | dspace |
| spelling | ntu-10356/1550612023-02-28T19:25:32Z Carbene-catalyzed enantioselective annulation of dinucleophilic hydrazones and bromoenals for access to aryl-dihydropyridazinones and related drugs Mondal, Bivas Maiti, Rakesh Yang, Xing Xu, Jun Tian, Weiyi Yan, Jia-Lei Li, Xiangyang Chi, Robin Yonggui School of Physical and Mathematical Sciences Science::Chemistry Molecules Reaction Intermediates 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. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) Nanyang Technological University National Research Foundation (NRF) Published version We acknowledge nancial support from the Singapore National Research Foundation under its NRF Investigatorship (NRF-NRFI2016-06) and Competitive Research Program (NRF-CRP22-2019-0002); the Ministry of Education, Singapore, under its MOE AcRF Tier 1 Award (RG108/16, RG5/ 19, RG1/18), MOE AcRF Tier 2 (MOE2019-T2-2-117), MOE AcRF Tier 3 Award (MOE2018-T3-1-003); the Agency for Science, Technology and Research (A*STAR) under its A*STAR AME IRG Award (A1783c0008, A1783c0010); GSK-EDB Trust Fund; Nanyang Research Award Grant, Nanyang Technological University; the National Natural Science Foundation of China (21772029, 21801051, 21807019, 21961006, 22071036, 22061007, 82360589, 81360589), Frontiers Science Center for Asymmetric Synthesis and Medicinal Molecules, Department of Education, Guizhou Province [Qianjiaohe KY number (2020) 004]; The 10 Talent Plan (Shicengci) of Guizhou Province ([2016] 5649); the Science and Technology Department of Guizhou Province ([2018]2802, [2019]1020); the National Natural Science Foundation of China (No. 31960546); the Program of Introducing Talents of Discipline to Universities of China (111 Program, D20023) at Guizhou University; the Guizhou Province First-Class Disciplines Project [(Yiliu Xueke Jianshe Xiangmu)- GNYL(2017)008], NSFC Grant (81360589), Guizhou University of Traditional Chinese Medicine (China); and Guizhou University 2022-02-04T06:22:05Z 2022-02-04T06:22:05Z 2021 Journal Article Mondal, B., Maiti, R., Yang, X., Xu, J., Tian, W., Yan, J., Li, X. & Chi, R. Y. (2021). Carbene-catalyzed enantioselective annulation of dinucleophilic hydrazones and bromoenals for access to aryl-dihydropyridazinones and related drugs. Chemical Science, 12(25), 8778-8783. https://dx.doi.org/10.1039/d1sc01891d 2041-6520 https://hdl.handle.net/10356/155061 10.1039/d1sc01891d 34257877 2-s2.0-85109096710 25 12 8778 8783 en NRF-NRFI2016-06 NRF-CRP22-2019-0002 RG108/16 RG5/19 RG1/18 MOE2019-T2-2-117 MOE2018-T3-1-003 A1783c0008 A1783c0010 Chemical Science © 2021 The Author(s). Published by the Royal Society of Chemistry. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. application/pdf |
| spellingShingle | Science::Chemistry Molecules Reaction Intermediates Mondal, Bivas Maiti, Rakesh Yang, Xing Xu, Jun Tian, Weiyi Yan, Jia-Lei Li, Xiangyang Chi, Robin Yonggui Carbene-catalyzed enantioselective annulation of dinucleophilic hydrazones and bromoenals for access to aryl-dihydropyridazinones and related drugs |
| title | Carbene-catalyzed enantioselective annulation of dinucleophilic hydrazones and bromoenals for access to aryl-dihydropyridazinones and related drugs |
| title_full | Carbene-catalyzed enantioselective annulation of dinucleophilic hydrazones and bromoenals for access to aryl-dihydropyridazinones and related drugs |
| title_fullStr | Carbene-catalyzed enantioselective annulation of dinucleophilic hydrazones and bromoenals for access to aryl-dihydropyridazinones and related drugs |
| title_full_unstemmed | Carbene-catalyzed enantioselective annulation of dinucleophilic hydrazones and bromoenals for access to aryl-dihydropyridazinones and related drugs |
| title_short | Carbene-catalyzed enantioselective annulation of dinucleophilic hydrazones and bromoenals for access to aryl-dihydropyridazinones and related drugs |
| title_sort | carbene catalyzed enantioselective annulation of dinucleophilic hydrazones and bromoenals for access to aryl dihydropyridazinones and related drugs |
| topic | Science::Chemistry Molecules Reaction Intermediates |
| url | https://hdl.handle.net/10356/155061 |
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