Photochemical methods are increasingly being used in organic synthesis. They are especially useful for preparing many compounds that are not readily accessible through thermal or enzymatic reactions. The supramolecular strategy has proved highly promising in recent years for manipulating the stereochemical outcome of chiral photoreactions through relatively strong and long-lasting noncovalent interactions in both ground and excited states. Among the numerous chiral photochemical reactions, photocyclodimerization of 2-anthracenecarboxylate (AC) is the most comprehensively studied supramolecular chiral photoreaction and has essentially become a benchmark reaction for evaluating supramolecular photochirogenesis. Cyclodextrin (CD) derivatives were the earliest and are the most widely applied chiral host for mediating photoreactions. Herein, we use CD-mediated photocyclodimerization of AC as an example to introduce the operation process of supramolecular chiral photoreactions. The protocol includes the following contents: (i) the preparation, purification and characterization of β-CD derivatives; (ii) methods for investigating the host–guest inclusion behavior between AC and β-CD derivatives; (iii) the photochemical reaction operation flow under different solvent and temperature conditions; (iv) chiral high-performance liquid chromatography (HPLC) analyses of the product distribution and enantioselectivity. The protocol is introduced by using representative examples of the synthesis of β-CD derivatives and the manipulation of environmental factors that give excellent regio- and enantioselectivities in the photocyclodimerization of AC. The synthesis and purification of β-CD derivatives require 3–5 d of work. The photoirradiation of AC with β-CD derivatives can be done within 1 h. The product analysis requires 5 h.
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We acknowledge the support of this work by the National Key Research and Development Program of China (2017YFA0505903), the National Natural Science Foundation of China (92056116, 22001046, 21871194, 21971169 and 21572142), the Fundamental Research Funds for the Central Universities (20826041D4117), the Comprehensive Training Platform of Specialized Laboratory (College of Chemistry, Sichuan University), the Department of Education, Science and Technology of Guangxi Zhuang Autonomous Region (2020KY03008, 2020AC19233 and 2021JJB120031) and the Youth Science Foundation of Guangxi Medical University (GXMUYSF201904).
The authors declare no competing interests.
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Key references using this protocol
Wei, X. et al. J. Am. Chem. Soc. 140, 3959–3974 (2018): https://doi.org/10.1021/jacs.7b12085
Ji, J. et al. J. Am. Chem. Soc. 141, 9225–9238 (2019): https://doi.org/10.1021/jacs.9b01993
Key data used in this protocol
Ji, J. et al. J. Am. Chem. Soc. 141, 9225–9238 (2019): https://doi.org/10.1021/jacs.9b01993
a,b, Photographs of the state of the pyridine solution containing 100 mM β-CD before (a) and after the addition of p-toluenesulfonyl chloride dissolved in pyridine for 4 h (b). The reaction mixture was vigorously stirred under Ar protection with an inflated Ar balloon.
a, Glassware setup for synthesis of 6A,6C-diiodo-β-CD 13 or 6A,6D-diiodo-β-CD 14. b, Iodination for 6A,6C-di-O-tosyl-β-CD 11 monitored by TLC (the TLC Rf values of 6A,6X-di-O-tosyl-β-CD and 6A,6X-diiodo-β-CD are 0.6 and 0.5, respectively, using isopropanol/EtOAc/H2O/NH3∙H2O (5:2:3:1 (vol/vol/vol/vol) as eluent).
Glassware setup for synthesis of 6A,6C-TMA2-β-CD 7 or 6A,6D-TMA2-β-CD 8.
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Wei, X., Ji, J., Nie, Y. et al. Synthesis of cyclodextrin derivatives for enantiodifferentiating photocyclodimerization of 2-anthracenecarboxylate. Nat Protoc 17, 2494–2516 (2022). https://doi.org/10.1038/s41596-022-00722-6