An Axially Chiral Salicylaldehyde-Based 19F NMR Probe for the Enantiomeric Discrimination of Chiral Amines

doi:10.6023/cjoc202603044

Chinese Journal of Organic Chemistry ›› 2026, Vol. 46 ›› Issue (9): 3704-3712.DOI: 10.6023/cjoc202603044 Previous Articles Next Articles

ARTICLE

基于轴手性水杨醛的¹⁹F NMR探针用于手性胺的对映体识别

彭天赐, 翁嘉劲, 谷广星, 赵延川^*()

中国科学院上海有机化学研究所沪港化学合成联合实验室上海 200032

收稿日期:2026-03-30 修回日期:2026-05-19 发布日期:2026-07-06
通讯作者: 赵延川
基金资助:
国家自然科学基金(22271305); 国家自然科学基金(22574168)

An Axially Chiral Salicylaldehyde-Based ¹⁹F NMR Probe for the Enantiomeric Discrimination of Chiral Amines

Tianci Peng, Jiajin Weng, Guangxing Gu, Yanchuan Zhao^*()

State Key Laboratory of Fluorine and Nitrogen Chemistry and Advanced Materials and Shanghai-Hong Kong Joint Laboratory in Chemical Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032

Received:2026-03-30 Revised:2026-05-19 Published:2026-07-06
Contact: Yanchuan Zhao
About author:
Dedicated to the 100th anniversary of the birth of Professor Xikui Jiang.
Supported by:
National Natural Science Foundation of China(22271305); National Natural Science Foundation of China(22574168)

1. .pdf(3321KB)

Abstract

A concise and broadly applicable strategy for the chiral analysis of primary amines by ¹⁹F NMR remains difficult to realize because an effective probe must integrate a rigid chiral environment, a fluorinated reporter, and a reactive site for fast analyte capture. S-BINOL-probe, an axially chiral salicylaldehyde derived from 1,1'-bi-2-naphthol (BINOL) and equipped with a trifluoroethoxy reporter, is reported in this work. The probe is prepared in a short sequence from commercially available starting materials and forms diastereomeric imine adducts that display well-resolved ¹⁹F NMR signals. S-BINOL-probe discriminates 15 chiral primary amines, a broad set of amino acids, multicomponent amino acid mixtures, and representative chiral amine drugs. The same platform also enables accurate determination of enantiomeric composition, and the measured ee exhibits excellent linear correlation with preset ee. These results identify S-BINOL-probe as a synthetically accessible and analytically useful ¹⁹F NMR sensing reagent for rapid chiral analysis.

Key words: ¹⁹F NMR, probe, chiral analysis, amino acids, enantiomeric excess

Cite this article

Tianci Peng, Jiajin Weng, Guangxing Gu, Yanchuan Zhao. An Axially Chiral Salicylaldehyde-Based ¹⁹F NMR Probe for the Enantiomeric Discrimination of Chiral Amines[J]. Chinese Journal of Organic Chemistry, 2026, 46(9): 3704-3712.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

Fig. & Tab. 7

Scheme 1. (a ~ c) Comparison of established 19F NMR derivatization strategies; (d) Axially chiral BINOL-derived dynamic covalent probe developed in this work

Scheme 2. Preparation of the 19F-Labeled derivatization reagent S-BINOL-probe

Figure 1. Chiral recognition of amine compounds by 19F NMR using the probe S-BINOL-probe The 19F NMR spectra of mixtures of S-BINOL-probe (2.54 mmol/L) with different racemic analytes (2.54 mmol/L) in CD3OD. The 19F NMR spectra were recorded on a Bruker AVANCE NEO 600 NMR spectrometer (565 MHz for 19F) with 32 scans.

Figure 2. Chiral discrimination of amines by 19F NMR using the probe S-BINOL-probe (a~k) 19F NMR spectra of mixtures containing S-BINOL-probe (2.54 mmol/L, pre-dissolved in 400 µL of CD3OD) and various racemic analytes (5.08 mmol/L, dissolved in 100 µL of H2O with 75.2 mmol/L NEt3), resulting in a final CD3OD/H2O (V∶V=4∶1); (l~p) 19F NMR spectra of mixtures containing S-BINOL-probe (2.54 mmol/L, pre-dissolved in 400 µL of DMSO-d6) and various racemic analytes (5.08 mmol/L, dissolved in 100 µL of H2O with 75.2 mmol/L NEt3), resulting in a final DMSO-d6/H2O (V∶V=4∶1). 19F NMR spectra were recorded on a Bruker AVANCE NEO 600 NMR spectrometer (565 MHz for 19F) with 32 scans.

Figure 3. 19F NMR spectra (32 scans) of mixtures of the probe S-BINOL-probe (2.54 mmol/L in CD3OD) and different analytes (5.08 mmol/L in H2O with 75.2 mmol/L NEt3) (a) Spectra obtained after pre-mixing the four amino acid analytes and then adding the mixture to probe S-BINOL-probe; (b~e) spectra of probe S-BINOL-probe bound to various amino acid compounds; (f) probe S-BINOL-probe alone.

Figure 4. Linear regression plot showing the relationship between the prepared ee and the ee of B8S measured using the probe S-BINOL-probe

Figure 5. (a~b) 19F NMR spectra of the probe S-BINOL-probe (2.54 mmol/L) mixed with various chiral amine drugs (5.08 mmol/L in H2O with 75.2 mmol/L NEt3) in DMSO-d6; (c~f) 19F NMR spectra of the probe S-BINOL-probe (2.54 mmol/L) mixed with various chiral amine drugs (5.08 mmol/L) in DMSO-d6

References 17

[1]	Cabré, A.; Verdaguer, X.; Riera, A. Chem. Rev. 2022, 122, 269. doi: 10.1021/acs.chemrev.1c00496
[2]	(a) Peluso, P.; Chankvetadze, B. Chem. Rev. 2022, 122, 13235. doi: 10.1021/acs.chemrev.1c00846 pmid: 35917234
	(b) Coelho, M. M.; Fernandes, C.; Remião, F.; Tiritan, M. E. Molecules 2021, 26, 3113. doi: 10.3390/molecules26113113 pmid: 35917234
[3]	Liu, H.; Wu, Z.; Chen, J.; Wang, J.; Qiu, H. J. Chromatogr. A 2023, 1708, 464367. doi: 10.1016/j.chroma.2023.464367
[4]	(a) Chai, Z.; Wang, W.; Chen, J.; Wu, Q.; Ma, L.; Liu, Z.; Xu, G.; Ling, J.; Shu, Y.; Liu, M.; Li, C. J. Am. Chem. Soc. 2026, 148, 9213. doi: 10.1021/jacs.5c21094
	(b) Cui, C.-Y.; Li, B.; Zhang, X.; Guo, S.-L.; Pan, B.-B.; Su, X.-C. J. Am. Chem. Soc. 2025, 147, 19893. doi: 10.1021/jacs.5c04351
	(c) Xu, Z.; Wang, C.; He, S.; Wu, J.; Zhao, Y. Angew. Chem. Int. Ed. 2025, 64, e202417112.
	(d) Chen, D.; Lin, Y.; Fan, Y.; Li, L.; Tan, C.; Wang, J.; Lin, H.; Gao, J. Angew. Chem. Int. Ed. 2023, 62, e202313753. doi: 10.1002/anie.v62.50
	(e) Zhu, W.; Monnie, C. M.; Kitoka, K.; Gronenborn, A. M. Angew. Chem. Int. Ed. 2025, 64, e202419709. doi: 10.1002/anie.v64.7
	(f) Meng, H.; Wen, L.; Xu, Z.; Li, Y.; Hao, J.; Zhao, Y. Org. Lett. 2019, 21, 5206. doi: 10.1021/acs.orglett.9b01813
[5]	(a) Wang, W.; Xia, X.; Bian, G.; Song, L. Chem. Commun. 2019, 55, 6098. doi: 10.1039/C9CC01942A
	(b) Weng, J.; Gu, G.; Zhang, W.; Jia, Q.; Sun, Y.; Wu, J.; Zhao, Y. Angew. Chem. Int. Ed. 2025, 64, e202505700. doi: 10.1002/anie.v64.32
[6]	Chen, Y.-T.; Li, B.; Chen, J.-L.; Su, X.-C. Analyst 2023, 148, 233. doi: 10.1039/D2AN01632J
[7]	Huang, B.; Xu, L.; Wang, N.; Ying, J.; Zhao, Y.; Huang, S. Anal. Chem. 2022, 94, 1867. doi: 10.1021/acs.analchem.1c04823
[8]	Jang, S.; Park, H.; Duong, Q. H.; Kwahk, E.-J.; Kim, H. Anal. Chem. 2022, 94, 1441. doi: 10.1021/acs.analchem.1c04834
[9]	(a) Gu, G.; Wang, C.; Zhao, Y. Synthesis 2025, 57, 1671. doi: 10.1055/a-2435-5962
	(b) Gu, G.; Xu, Z.; Yu, N.; Zhao, Y. Coord. Chem. Rev. 2026, 551, 217454. doi: 10.1016/j.ccr.2025.217454
[10]	(a) Zhou, Y.; Ren, Y.; Zhang, L.; You, L.; Yuan, Y.; Anslyn, E. V. Tetrahedron 2015, 71, 3515. doi: 10.1016/j.tet.2015.03.121
	(b) Ni, C.; Zha, D.; Ye, H.; Hai, Y.; Zhou, Y.; Anslyn, E. V.; You, L. Angew. Chem. Int. Ed. 2018, 57, 1300. doi: 10.1002/anie.v57.5
	(c) You, L.; Berman, J. S.; Anslyn, E. V. Nat. Chem. 2011, 3, 943. doi: 10.1038/nchem.1198
[11]	Kriegelstein, M.; Profous, D.; Lyčka, A.; Trávníček, Z.; Přibylka, A.; Volná, T.; Benická, S.; Cankař, P. J. Org. Chem. 2019, 84, 11911. doi: 10.1021/acs.joc.9b01770 pmid: 31449414
[12]	Dale, J. A.; Mosher, H. S. J. Am. Chem. Soc. 1973, 95, 512. doi: 10.1021/ja00783a034
[13]	(a) Jolliffe, J. D.; Armstrong, R. J.; Smith, M. D. Nat. Chem. 2017, 9, 558. doi: 10.1038/nchem.2710 pmid: 28537599
	(b) Pu, L. Chem. Rev. 2024, 124, 6643. doi: 10.1021/acs.chemrev.4c00132 pmid: 28537599
[14]	(a) Pu, L. Acc. Chem. Res. 2012, 45, 150. doi: 10.1021/ar200048d
	(b) Pu, L.; Senge, M. O.; Olmstead, M. M.; Power, P. P. J. Am. Chem. Soc. 1998, 120, 12682. doi: 10.1021/ja982717g
	(c) Yu, H.-B.; Hu, Q.-S.; Pu, L. J. Am. Chem. Soc. 2000, 122, 6500. doi: 10.1021/ja000778k
	(d) Pu, L. Chem. Rev. 2004, 104, 1687. doi: 10.1021/cr030052h
[15]	Li, Y.; Wen, L.; Meng, H.; Lv, J.; Luo, G.; Zhao, Y. Cell Rep. Phys. Sci. 2020, 1, 100100.
[16]	Ma, Z.; Gu, G.; Zeng, Y.; Weng, J.; Bao, W.; Zhao, Y. Talanta 2026, 298, 129057. doi: 10.1016/j.talanta.2025.129057
[17]	(a) Li, H.; Xu, Z.; Zhang, S.; Jia, Y.; Zhao, Y. Anal. Chem. 2022, 94, 2023. doi: 10.1021/acs.analchem.1c03783
	(b) Dong, C.; Xu, Z.; Wen, L.; He, S.; Wu, J.; Deng, Q.-H.; Zhao, Y. Anal. Chem. 2021, 93, 2968. doi: 10.1021/acs.analchem.0c04768

基于轴手性水杨醛的¹⁹F NMR探针用于手性胺的对映体识别

An Axially Chiral Salicylaldehyde-Based ¹⁹F NMR Probe for the Enantiomeric Discrimination of Chiral Amines

RichHTML

PDF

Supporting Info.

Knowledge

Abstract

Cite this article

share this article

Fig. & Tab. 7

References 17

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	Zhongshan Xiao, Han Wang, Lu Xu, Ruijuan He, Guojing Yang, Yakun Wang, Zhaomin Liu, Tao Zhang. A Novel Phosphate-Ester-Phenothiazine Fluorescent Probe for Detection and Imaging of Sulfur Dioxide Derivatives [J]. Chinese Journal of Organic Chemistry, 2026, 46(8): 3068-3078.
[2]	Guiyuan Chen, Shengyu Li, Jilin Guo, Xiang Wang, Yetong Liu, Beining Xiao, Zhaoyang Wang. Research Progress in Synthesis and Application of 3-Cyanopyridines [J]. Chinese Journal of Organic Chemistry, 2026, 46(6): 2227-2240.
[3]	Bailin Guo, Sainü Wang, Bingxin Lei, Enju Wang. A Wash-Free Cell Membrane Fluorescent Probe Based on Monomer-Excimer Conversion [J]. Chinese Journal of Organic Chemistry, 2026, 46(5): 2082-2089.
[4]	Jidong Zhang, Hao Wang, Xiaoxin Quan, Shenghai Zhang, Wei She. Synthesis of Aggregation-Induced Emission (AIE) Organic Polymorphs Based on Tetraphenylethene Structure: Research on Molecular Conformation and Detection Performance of Cys [J]. Chinese Journal of Organic Chemistry, 2026, 46(3): 934-940.
[5]	Lin Liu, Lulu Zhou, Tianyu Liang, Keli Zhong, Xiaomei Yan, Lijun Tang. Near-Infrared Fluorescent Probe Based on Benzopyran Derivative for Highly Sensitive Detection of SO₂ Derivative and Bioimaging [J]. Chinese Journal of Organic Chemistry, 2026, 46(3): 866-871.
[6]	Xiaofei Sun, Haiyuan Zhang, Juan Li, Ji Ma, Ruoxi Wang, Keli Zhong, Xuepeng Li, Tianyu Liang, Lijun Tang, Jianrong Li. Application of an Intelligent Integrated Platform Based on “OFF-ON” Fluorescent Probe in Salmon Freshness Monitoring [J]. Chinese Journal of Organic Chemistry, 2026, 46(2): 586-593.
[7]	Ke Ren, Guanglu Zhang, Yifan Niu, Xiaomeng Wang, Canyu Chen, Min Jiang. Photocatalytic Radical-Mediated Synthesis of Unnatural α-Amino Acids from Heteroaryl Aldehydes [J]. Chinese Journal of Organic Chemistry, 2026, 46(1): 215-224.
[8]	Zhijie Jiang, Jinxiu Chen, Xiaofei Zhu, Xinhao Deng, Qiongjiao Yan, Wei Wang, Hui Zhou. Recent Advances on the Functionalization of Azlactones at Different Reactive Sites [J]. Chinese Journal of Organic Chemistry, 2026, 46(1): 1-20.
[9]	Aopei Peng, Yang Li, Yuanyuan Zhu, Guangwen Wu, Shuangxi Gu. Advances in Chemoselective Recognition of Amino Acids by Schiff Base Fluorescent Probes [J]. Chinese Journal of Organic Chemistry, 2025, 45(9): 3301-3313.
[10]	Zhaozhou Li, Yafang Xie, Jian Tao, Xuebing Wei, Lele Li, Yajuan Li, Jiamin Tang, Huawei Niu, Xiujin Chen, Hongli Gao, Fang Li, Huichun Yu, Yunxia Yuan, Shaobin Gu, Huaibin Kang, Xiaofei Sun, Guoyan Ren, Ying Wu. Construction of Cysteine Fluorescent Probes and Their Applications in Pathological Examination [J]. Chinese Journal of Organic Chemistry, 2025, 45(7): 2335-2349.
[11]	Qing Shen, Yu Zeng, Zhonghao Li, Xiying Cao, Yuting Guo, Yunyi Ye, Zhaoyang Wang. Research Progress on Reactive Small Molecule Fluorescent Probes Based on the Formation and Cleavage of Covalent Bond [J]. Chinese Journal of Organic Chemistry, 2025, 45(4): 1194-1205.
[12]	Wenbo Zhang, Siming Su, Peng Yang. Synthesis of A Novel Calix[3]carbazole Derivative and Its Recognition and Detection of 10-Hydroxycamptothecin [J]. Chinese Journal of Organic Chemistry, 2025, 45(4): 1395-1401.
[13]	Hanyue Xiang, Shaoyin Wei, Yuji Wang, Nao Xiao. Recent Advances of Fe(II) Fluorescence Probes Based on N-Oxide Structure [J]. Chinese Journal of Organic Chemistry, 2025, 45(4): 1137-1152.
[14]	Xiaohong Cheng, Renjie Zhang, Jun You, Wenbin Fu, Wenjie Shen, Yunqiang Luo, Song Wang. A Novel Catalytic Fluorescent Probe and Its Application in Copper Detection in Gas-Generating Agents [J]. Chinese Journal of Organic Chemistry, 2025, 45(11): 4195-4201.
[15]	Bingyan Chen, Jie Sun, Linghong Xiong, Xuewen He. Fluorescence Light-Up Detection and Imaging of Atypical Nucleic Acid Structures [J]. Chinese Journal of Organic Chemistry, 2025, 45(11): 4082-4107.

基于轴手性水杨醛的19F NMR探针用于手性胺的对映体识别