Catalytic atroposelective synthesis of axially chiral benzonitriles via chirality control during bond dissociation and CN group formation
The applications of axially chiral benzonitriles and their derivatives remain mostly unexplored due to their synthetic difficulties. Here we disclose an unusual strategy for atroposelective access to benzonitriles via formation of the nitrile unit on biaryl scaffolds pre-installed with stereogenic a...
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Science::Chemistry Catalyst Chemical Bonding Lv, Ya Luo, Guoyong Liu, Qian Jin, Zhichao Zhang, Xinglong Chi, Robin Yonggui Catalytic atroposelective synthesis of axially chiral benzonitriles via chirality control during bond dissociation and CN group formation |
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The applications of axially chiral benzonitriles and their derivatives remain mostly unexplored due to their synthetic difficulties. Here we disclose an unusual strategy for atroposelective access to benzonitriles via formation of the nitrile unit on biaryl scaffolds pre-installed with stereogenic axes in racemic forms. Our method starts with racemic 2-arylbenzaldehydes and sulfonamides as the substrates and N-heterocyclic carbenes as the organocatalysts to afford axially chiral benzonitriles in good to excellent yields and enantioselectivities. DFT calculations suggest that the loss of p-toluenesulfinate group is both the rate-determining and stereo-determining step. The axial chirality is controlled during the bond dissociation and CN group formation. The reaction features a dynamic kinetic resolution process modulated by both covalent and non-covalent catalytic interactions. The axially chiral benzonitriles from our method can be easily converted to a large set of functional molecules that show promising catalytic activities for chemical syntheses and anti-bacterial activities for plant protections. |
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School of Physical and Mathematical Sciences |
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School of Physical and Mathematical Sciences Lv, Ya Luo, Guoyong Liu, Qian Jin, Zhichao Zhang, Xinglong Chi, Robin Yonggui |
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Lv, Ya Luo, Guoyong Liu, Qian Jin, Zhichao Zhang, Xinglong Chi, Robin Yonggui |
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Lv, Ya |
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Catalytic atroposelective synthesis of axially chiral benzonitriles via chirality control during bond dissociation and CN group formation |
title_short |
Catalytic atroposelective synthesis of axially chiral benzonitriles via chirality control during bond dissociation and CN group formation |
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Catalytic atroposelective synthesis of axially chiral benzonitriles via chirality control during bond dissociation and CN group formation |
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Catalytic atroposelective synthesis of axially chiral benzonitriles via chirality control during bond dissociation and CN group formation |
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Catalytic atroposelective synthesis of axially chiral benzonitriles via chirality control during bond dissociation and CN group formation |
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catalytic atroposelective synthesis of axially chiral benzonitriles via chirality control during bond dissociation and cn group formation |
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2022 |
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https://hdl.handle.net/10356/155057 |
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sg-ntu-dr.10356-1550572023-02-28T19:58:09Z Catalytic atroposelective synthesis of axially chiral benzonitriles via chirality control during bond dissociation and CN group formation Lv, Ya Luo, Guoyong Liu, Qian Jin, Zhichao Zhang, Xinglong Chi, Robin Yonggui School of Physical and Mathematical Sciences Science::Chemistry Catalyst Chemical Bonding The applications of axially chiral benzonitriles and their derivatives remain mostly unexplored due to their synthetic difficulties. Here we disclose an unusual strategy for atroposelective access to benzonitriles via formation of the nitrile unit on biaryl scaffolds pre-installed with stereogenic axes in racemic forms. Our method starts with racemic 2-arylbenzaldehydes and sulfonamides as the substrates and N-heterocyclic carbenes as the organocatalysts to afford axially chiral benzonitriles in good to excellent yields and enantioselectivities. DFT calculations suggest that the loss of p-toluenesulfinate group is both the rate-determining and stereo-determining step. The axial chirality is controlled during the bond dissociation and CN group formation. The reaction features a dynamic kinetic resolution process modulated by both covalent and non-covalent catalytic interactions. The axially chiral benzonitriles from our method can be easily converted to a large set of functional molecules that show promising catalytic activities for chemical syntheses and anti-bacterial activities for plant protections. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) Nanyang Technological University National Research Foundation (NRF) Published version We acknowledge financial support from the National Natural Science Foundation of China (21772029, 21801051, 21961006, and 22001173), The ten Talent Plan (Shicengci) of Guizhou Province ([2016]5649), the Science and Technology Department of Guizhou Province ([2019]1020, Qiankehejichu-ZK[2021]Key033), the Program of Introducing Talents of Discipline to Universities of China (111 Program, D20023) at Guizhou University, Frontiers Science Center for Asymmetric Synthesis and Medicinal Molecules, Department of Education, Guizhou Province [Qianjiaohe KY (2020)004], the Basic and Applied Research Foundation of Guangdong Province (2019A1515110906), the Guizhou Province First-Class Disciplines Project [(Yiliu Xueke Jianshe Xiangmu)-GNYL(2017) 008], Guizhou University of Traditional Chinese Medicine, and Guizhou University (China). Singapore National Research Foundation under its NRF Investigatorship (NRFNRFI2016-06) and Competitive Research Program (NRF-CRP22-2019-0002); the Ministry of Education, Singapore, under its MOE AcRF Tier 1 Award (RG7/20, RG5/19), MOE AcRF Tier 2 (MOE2019-T2-2-117), MOE AcRF Tier 3 Award (MOE2018-T3-1- 003); Nanyang Research Award Grant, Chair Professorship Grant, Nanyang Technological University. X.Z. acknowledges the support from IHPC, A*STAR, and thanks to the Deputy Chief Executive Research Office (DCERO), A*STAR for a Career Development Fund (CDF Project Number C210812008) for this work. X.Z. acknowledges the partial use of supercomputers in the A*STAR Computational Resource Center (ACRC) for computations performed in this work. 2022-02-03T08:48:07Z 2022-02-03T08:48:07Z 2022 Journal Article Lv, Y., Luo, G., Liu, Q., Jin, Z., Zhang, X. & Chi, R. Y. (2022). Catalytic atroposelective synthesis of axially chiral benzonitriles via chirality control during bond dissociation and CN group formation. Nature Communications, 13(1), 36-. https://dx.doi.org/10.1038/s41467-021-27813-4 2041-1723 https://hdl.handle.net/10356/155057 10.1038/s41467-021-27813-4 35013312 2-s2.0-85122672935 1 13 36 en NRFNRFI2016-06 NRF-CRP22-2019-0002 RG7/20 RG5/19 MOE2019-T2-2-117 MOE2018-T3-1- 003 Nature Communications © 2022 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/. application/pdf |