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Nat Commun
Nat Commun
Nature Communications
2041-1723
Nature Publishing Group UK London

52133
10.1038/s41467-024-52133-8
Article
Simultaneous construction of inherent and axial chirality by cobalt-catalyzed enantioselective C-H activation of calix[4]arenes
Li Tong 1
Zhang Yanbo 1
Du Cong 2
http://orcid.org/0000-0002-1880-8417
Yang Dandan yangdandan@zzu.edu.cn

1
Song Mao-Ping 1
http://orcid.org/0000-0001-8012-4676
Niu Jun-Long niujunlong@zzu.edu.cn

1
1 https://ror.org/04ypx8c21 grid.207374.5 0000 0001 2189 3846 College of Chemistry, Pingyuan Laboratory, Zhengzhou University, Zhengzhou, China
2 https://ror.org/003xyzq10 grid.256922.8 0000 0000 9139 560X School of Materials Science and Engineering, and Collaborative Innovation Center of Nano Functional Materials and Applications, Henan University, Kaifeng, China
3 9 2024
3 9 2024
2024
15 767321 5 2024
27 8 2024
© The Author(s) 2024
2024
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The simultaneous construction of multiple stereogenic elements in a single step is highly appealing and desirable in the field of asymmetric synthesis. Furthermore, the catalytic enantioselective synthesis of inherently chiral calix[n]arenes with high enantiopurity has long been a challenging endeavor. Herein, we report an enantioselective cobalt-catalyzed C–H activation/annulation for the efficient construction of inherently chiral calix[4]arenes bearing multiple C–N axially chiral element. By employing the benzamide tethered calix[4]arene as the substrate, the C–H annulation with alkynes can be successfully accomplished, leading to the generation of multiple stereogenic elements. A wide range of calix[4]arenes and alkynes are found to be well compatible, and exhibit good yields, high enantioselectivity and excellent diastereoselectivity. Notably, the gram-scale reaction, catalytic application, synthetic transformations, and chiral recognition further showcase the potential applications of this protocol.

The catalytic enantioselective synthesis of inherently chiral calix[n]arenes with high enantiopurity has long been a challenging endeavor. Herein, the authors report an enantioselective cobalt-catalyzed C–H activation/annulation for the efficient construction of inherently chiral calix[4]arenes bearing multiple C–N axially chiral element.

Subject terms

Stereochemistry
Synthetic chemistry methodology
Asymmetric catalysis
https://doi.org/10.13039/501100001809 National Natural Science Foundation of China (National Science Foundation of China) 22271260 Niu Jun-Long Key Projects of the Joint Fund for Science and Technology of Henan Province (232301420007 to J.-L.N.); Excellent Youth Foundation of Henan Scientific Committee (242300421033 to J.-L.N.),Postdoctoral Foundation of Henan Province (HN2024006 to D.Y.)issue-copyright-statement© Springer Nature Limited 2024
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pmcIntroduction

Inherent chirality, as a unique form of chirality, characterizes the three-dimensional curved architecture of macrocycles, distinguishing them from other well-known chiral molecules bearing a common central, axial, planar, and helical chirality (Fig. 1a)1–8. Among them, inherently chiral calix[n]arenes have been widely recognized as a prominent group owing to their controllable cavity shape, adjustable sizes, and convenient post-modification benefits (Fig. 1b). These distinctive features have showcased their significant potential in chiral recognition, sensing and nanotechnology9–23. However, the synthesis of inherently chiral calix[n]arenes with high enantioselectivities remains a formidable challenge24–39. Previous methods typically relied on the use of small-scale chiral HPLC separation or the complicated introduction of a stoichiometric amount of a chiral auxiliary to obtain enantiomers with either low efficiency or limited enantioselectivity40–50. Alternatively, catalytic enantioselective synthesis represents an effective and straightforward means, but it is undoubtfully very challenging with limited success in this field7,51–56. In 2009, Tsue group developed the Pd-catalyzed intramolecular C–N bond forming macrocyclization to synthesize inherently chiral azacalix[4]arene, albeit with an ee value of only 35%53. Notably, Wang and Tong group achieved an efficient Pd-catalyzed synthesis of highly enantiopure ABCD-type heteracalix[4]-aromatics via a catalytic intramolecular C–N cross coupling reaction (Fig. 1c, left)54. In addition, desymmetrization is an alternative method for accessing chiral calix[n]arenes, with only two reported attempts to date. The Cai group has made significant progress in the enantioselective synthesis of chiral calix[4]arenes through Pd-catalyzed intramolecular C–H arylation (Fig. 1c, right)55. Almost simultaneously, the Wang and Tong group reported another example involving a Pd-catalyzed enantioselective dehydrogenative cross-coupling to access inherently chiral calixarenes (Fig. 1c, right)56. Despite these achievements, this field still lags far behind the catalytic asymmetric synthesis of compounds with common chiral elements, leaving ample room for further growth. Additionally, the few existing reports relied heavily on intramolecular reactions catalyzed by precious palladium catalysts, rendering it highly desirable to explore a new catalytic strategy utilizing earth-abundant metal catalysts57–63. Moreover, the introduction of additional stereogenic elements, such as C–C or C–N axial chirality, into inherently chiral calix[n]arenes offers the potential to expand their versatile applications by incorporating new properties and improvements to these chiral macrocycles.Fig. 1 Background and project synopsis.

a Common chiral elements (well-developed). b Inherently chiral calix[n]arenes. c Previous work: Catalytic asymmetric synthesis of chiral calix[n]arenes (Cai, Wang and Tong groups). d This work: Synthesis of inherently chiral calix[4]arenes with multiple C-N axially chiral element by Co(II)-catalyzed C-H/N-H annulation.

The construction of axially chiral compounds has recently garnered much attention due to their intriguing scaffolds and versatile applications64–76. Transition-metal-catalyzed enantioselective C–H functionalization offers a straightforward and powerful tool for the construction of axially chiral molecules77–82. Notably, significant advancements have recently been made in the enantioselective construction of C–C, C–N, and N–N atropisomers through earth-abundant cobalt-catalyzed C–H activation, which holds the advantage of using commercially available cobalt salt as the catalyst, along with a readily prepared and modified chiral ligand83–91. Nevertheless, the simultaneous asymmetric construction of multiple stereogenic elements through C–H activation in one step is undoubtedly more challenging. This imposes higher requirements on both asymmetric catalytic systems and ingenious substrate design. Typically, there has been an emerging interest in the enantioselective synthesis of atropisomers that possess multiple chiral elements, such as central, axial, planar, and helical chirality92–98. However, the catalytic assembly of enantiopure axially chiral compounds with additional inherent chirality has not yet been achieved. The formidable challenge of this project lies in simultaneously inducing inherent chirality and axial chirality in a single step, while also controlling both enantioselectivity and diastereoselectivity during the formation of multiple stereogenic elements. To tackle these challenges, here we established a cobalt/Salox-catalyzed enantioselective intermolecular C–H activation/annulation with alkynes, using benzamide tethered to calix[4]arene as substrates (Fig. 1d). By incorporating a 2-aminopyridine 1-oxide (PyO) directing group99–101 and using cost-effective Co(OAc)2·4H2O as the catalyst, this approach enables the construction of inherently chiral calix[4]arenes with an additional C–N axially chiral element, and exhibits high enantio- and diastereoselectivities. Notably, the chiral resolution tests based on inherently chiral calix[4]arenes exhibit diverse host-guest stereoselectivity towards a series of axial chiral binaphthols. In addition, the product obtained by combining host and guest was potential candidate material for CPL application.

Results

Optimizing Reaction Conditions

We initiated the studies by using the calix[4]arene tethered with benzamide 1a and alkyne 2a as substrates for the C–H activation/annulation reaction. The protocol operates under mild conditions with Co(OAc)2·4H2O as the catalyst and O2 as the oxidant. With the 2-aminopyridine 1-oxide (PyO) or 8-aminoquinoline (AQ) as the directing group, the results by using different chiral ligands were shown in Fig. 2. With PyO as the directing group, the desired inherently chiral product 3aa, with multiple C-N axial chirality was successfully obtained in a 89% yield and 90% ee value, when L1 was used as the chiral ligand. It is worth noting that the reaction displayed remarkably high diastereoselectivity, as evidenced by the presence of only one pair of enantiomers in the chiral HPLC analysis and the absence of any diastereomers. Subsequently, the substituents on the chiral salox ligand were then evaluated, and the ligand L2 bearing a methyl group at ortho-position of phenolic ring gave an improved result of 94% yield and 90% ee. After further optimization of the additive, cobalt catalyst, ligand loading, reaction time, and the ratio of reactants, the product 3aa was obtained in a yield of 90% and an ee value of 92% (see Supplementary Table 1). Meanwhile, the investigation was focused on the directing group tethered to the calix[4]arene. It was found that calix[4]arene, when linked with an 8-aminoquinoline auxiliary, could not be converted into the annulation product under standard conditions. After optimizing the reaction conditions (see Supplementary Table 2), including solvent, additive, and chiral ligand, the reaction gave the best result of 55% yield with low enantiomeric excess of 53%, and the diastereomeric ratio was only 1:1.4, with L2 as the chiral ligand. When other ligands (L1, L3–L8) are employed, neither the enantiomeric excess nor the diastereomeric ratio exhibits any significant improvement, all much lower than the results achieved with the PyO directing group. These findings further highlight the advantages and broad applicability of the 2-aminopyridine 1-oxide (PyO) directing group.Fig. 2 The survey of different directing groups and chiral ligands.

Reaction conditions for substrate 1a with PyO (2-aminopyridine 1-oxide) directing group: 1a (0.05 mmol), 2a (1.5 equiv), Co(OAc)2·4H2O (10 mol%), L (10 mol%), NaOPiv·H2O (2 equiv) in PhF (0.5 mL) at 80 °C under O2 for 6 h, isolated yield. Reaction conditions for substrate 1a’ with AQ (8-aminoquinoline) directing group: 1a’ (0.05 mmol), 2a (1.5 equiv), Co(OAc)2·4H2O (10 mol%), L (15 mol%), in DME (0.5 mL) at 80 °C under O2 for 6 h, isolated yield. DG, directing group; ee, enantiomeric excess; dr, diastereomeric ratio; DME, 1, 2-Dimethoxyethane.

Substrate scope

With the optimal conditions at our disposal, the scope of the alkyne substrates was also evaluated (Fig. 3). A wide range of alkynes containing halogen (−F, −Cl, −Br, −I), electron-withdrawing (−CF3, −CO2Me) or electron-donating (−Me, −OMe, −Ph, −C ≡ CH) groups at the para-position were tolerated to deliver the products 3ab-3ak in good yields of 44–91% and high enantioselectivities of 90–96%. The absolute configuration of inherently chiral 3ac with C − N axial chirality was determined by X-ray diffraction analysis (CCDC 2328817). The meta- or sterically hindered ortho- substituted alkynes 2l-2o also reacted smoothly to give the products 3al-3ao with high level of enantiopurities (92–95% ee). Moreover, the disubstituted alkynes were suitable partners, and the corresponding products 3ap-3aq were afforded in 86–87% yields and 90% ee. Typically, the alkynes 2r-2t bearing a heteroaromatic thiophene, or naphthyl unit also underwent effective annulations to give the products 3ar-3at in high yields and enantioselectivities. When 2, 7-diethynylpyrene 2 u containing two alkynyl moieties was used as a coupling partner, only one alkynyl group participated in the annulation, leading to the formation of 3au in 81% yield and 90% ee. Notably, alkynes 2 v and 2w, which are connected to a natural product structure of optically pure citronellol or menthol, underwent annulation actively to afford the products 3av and 3aw in 85% yield with 93% de and 90% yield with 91% de, respectively. Moreover, terminal alkynes substituted with cyclohexenyl and ester functional groups could also be converted to the desired products, further demonstrating the robustness of the protocol. Nevertheless, the terminal alkynes substituted with an alkyl chain could not be converted to the desired annulation product. And internal alkynes are also not compatible with this system, possibly due to steric hindrance caused by the calix[4]arene framework.Fig. 3 Scope of alkynes.

Reaction conditions: 1a (0.1 mmol), 2 (0.2 mmol), Co(OAc)2·4H2O (10 mol%), L2 (15 mol%), NaOPiv·H2O (0.2 mmol) in PhF (1 mL) at 80 °C under O2 for 8 h, isolated yields. ee, enantiomeric excess; de, diastereomeric excess.

Subsequently, we proceeded to investigate the substrate generality of calix[4]arene. As shown in Fig. 4, the incorporation of a halogen group (−Cl or −Br) at the C5 position of the pyridine N-oxide (PyO) ring facilitated successful annulation with alkynes, affording products 3ba and 3ca with good yields and high enantioselectivities (86% yield with 94% ee for 3ba, 80% yield with 94% ee for 3ca). By incorporating an electron-donating group (−Ph) at the C5 position of the PyO ring, the reaction gave the product 3da in 44% yield with 93% ee under slightly modified conditions. Replacing the methyl group with an ester group (−CO2Me) at the C3 position of the PyO ring also enabled efficient transformation, and the product 3ea was obtained in 88% yield and 96% enantioselectivity. Substrates bearing an ethoxy or n-butoxy group on the calix[4]arene are compatible with the protocol, resulting in the formation of inherently chiral products 3fa-3ga with a high degree of enantiocontrol (93–96% ee). Additionally, the substrate 1 h, which has tribromo groups on the calix[4]arene, underwent the annulation to furnish product 3 ha in 40% yield with 85% ee value.Fig. 4 Scope of calix[4]arene.

Reaction conditions: 1 (0.1 mmol), 2a (0.2 mmol), Co(OAc)2·4H2O (10 mol%), L2 (15 mol%), NaOPiv·H2O (0.2 mmol) in PhF (1 mL) at 80 °C under O2 for 8 h, isolated yieldsb.Co(OAc)2·4H2O (20 mol%), L2 (30 mol%). ee, enantiomeric excess.

Investigation on the stability of products

In order to study on the conformational stability of the products bearing a C-N chiral axis, the racemization experiments were conducted. It was found that the ee value of 3aa was decreased by 4% when heated at 120 °C in dodecane for 10 h. And the rotational barrier of 3aa was calculated to be 34.4 kcal/mol, and the half-life t1/2 of 3aa was determined to be 3.0 × 104 years at 25 °C. Accordingly, the rotational barrier and the half-life for 3au [∆G≠rot = 34.7 kcal/mol, t1/2 (25 °C) = 4.9 × 104 years], 3ax [∆G≠rot = 33.9 kcal/mol, t1/2 (25 °C) = 1.2 × 104 years], and 3ay [∆G≠rot = 33.7 kcal/mol, t1/2 (25 °C) =8.4 × 103 years] were calculated and shown in Fig. 5, which indicated the good atropostabilities of the products.Fig. 5 Investigation on the product stability.

The rotation barrier and the t1/2 of 3aa, 3au, 3ax, and 3ay.

Enantioselective recognition of binaphthol derivatives

To explore the application of the obtained calix[4]arenes, we conducted enantiomer recognition experiment by using 3aa as the host molecule and selected chiral binaphthols with the C2 symmetric chiral characteristic as the guest molecules. As shown in Fig. 6a, when combined with R-BINOLs, the fluorescence intensity of 3aa exhibited significant enhancements compared to the mixture of 3aa and S-BINOLs (see Supplementary Fig. 9 for details). To clarify the internal reasons for the process1,H NMR experiments were undertaken to assess the chiral recognition properties between receptor 3aa and chiral guests. As shown in Fig. 6b, the CH proton of 3aa at 8.09 ppm underwent a upfield chemical shift when treated with R-BINOL1, indicating 3aa captured R-BINOL1. In contrast, S-BINOL1 addition caused no significant changes. Furthermore1,H NMR titration experiments provided credible evidence for the binding of R-BINOL1 and 3aa. In Fig. 6c, the CH signal of 3aa exhibits notable changes along with the increased guest concentration, while the addition of S-BINOL1 to the CDCl3 solution of 3aa yields no changes in 1H signal (see Supplementary Fig. 10). We hypothesize that this is attributed to the hydrogen bonding between the host and guest molecules. To verify this theory, a 1HNMR analysis of 1:1 mixture of (R)-( + )−2,2’-dimethoxy-1,1’-binaphthyl and 3aa was performed. The results suggest that 3aa cannot recognize the binaphthol without hydroxyl groups (see Supplementary Fig. 11), thus further confirming our hypothesis. In addition, the Job’s plot analysis through NMR titration method revealed that 3aa formed a 1:1 complex with the R-BINOL1 (see Supplementary Fig. 12). To investigate whether the N-oxide moiety plays a role in the recognition of binaphthols, we conducted the experiment to reduce the N-oxide moiety to pyridine, by using 3aa as the substrate. However, it was found that a pair of diastereoisomers for the deoxidation products were obtained with 1.8:1 diastereomeric ratio (d.r.), and the isolation of the pure diastereoisomers was not feasible due to the facile rotation around the C–N axis. (see Supplementary Fig. 13). Finally, the CPL spectra of 3aa and R-BINOL1 as well as their enantiomers 3aa’ and S-BINOL1 exhibit as decent mirror images (see Supplementary Fig. 15). Its dissymmetry factors |glum| is about 2 × 10−4 around the emission maxima.Fig. 6 Enantioselective recognition of binaphthol derivatives.

a Ratio of luminescent intensity after adding R-BINOL derivatives (gray column) and S-BINOL derivatives (orange column) into the MeCN solution of 3aa. b 1H NMR (600 MHz, CDCl3, 22 °C) spectra of 3aa and BINOL1. c 1H NMR titration for the interaction of R-BINOL1 and 3aa: illustrating the chemical shift change.

Synthetic applications

In order to further explore the applicability of the sequential protocol, we conducted the model reaction on a gram-scasle using 1.11 g of 1a. The desired product 3aa was obtained with a high yield of 87% under standard conditions, maintaining an enantioselectivity of 92% ee (Fig. 7a). Moreover, the inherently chiral 3aa exhibited potential as a suitable chiral ligand for palladium-catalyzed enantioselective C-H functionalization, resulting in the desired product 6 in 81% yield and 60% ee (Fig. 7b). Furthermore, 3aa reacted readily with aldehyde reagents to deliver the product 4 without loss of enantiomeric excess (76% yield, 92% ee). And compound 4 could be further reduced to product 5 almost quantitatively with a yield of 98% and an ee value of 92% (Fig. 7c). Additionally, the allene substrate was evaluated for this protocol. It was found that ester substituted allene could smoothly reacted with 1a to deliver annulation product 7 with high ee value of 93% (Fig. 7d). Based on our previous studies on the cobalt-catalyzed atroposelective C-H activation/annulation83–87, we proposed a plausible mechanism, as depicted in Fig. 7e. First, in the presence of an O2 oxidant, a chiral ligand and a tBuCOONa, the Co(II) catalyst is oxidized to form the active Co(III) species. Substrate 1a coordinates with Co(III) to delivered the intermediate A, and A undergoes C-H activation, resulting in the formation of cyclometalated Co(III) intermediate B. In contrast, the formation of intermediate B’ is hindered due to the greater steric hindrance between the chiral ligand and the calixarene skeleton. Therefore, this C–H activation step might be responsible for determining the stereochemistry of the inherent chirality. Subsequently, alkyne 2a coordinates to the cobalt center and undergoes migratory insertion to furnish the seven-membered cobaltacycle intermediate C. Finally, the reductive elimination of C leads to the construction of the inherently chiral product 3aa with multiple C-N axial chirality via TS-1. Based on our previous axially chiral studies, the reductive elimination step could serve as a stereo-determining step for producing the C-N axial chirality83.Fig. 7 Synthetic applications and proposed mechanism.

a Gram-scale experiment. b Application of 3aa as ligand for Pd-catalyzed asymmetric C-H activation. c Synthetic transformations of 3aa. d Investigation of allene substrate. e Proposed mechanism. ee, enantiomeric excess; DCM, dichloromethane.

In conclusion, we have disclosed a catalytic C–H activation strategy that enables the facile synthesis of inherently chiral calix[4]arenes with multiple C–N axial chirality. The protocol was accomplished through ingenious substrate design, which involved the incorporation of a 2-aminopyridine 1-oxide (PyO) directing group into the calix[4]arene framework. By utilizing the earth-abundant and readily available cobalt salt as the catalyst, the intermolecular C–H/N–H annulation with alkynes was efficiently achieved and it demonstrated high enantioselectivity (up to 96% ee) and excellent diastereoselectivity (all > 20:1), resulting in the formation of multiple stereogenic elements. A broad range of calix[4]arenes as well as alkynes were evaluated and found to be well tolerated under mild conditions. The gram-scale reaction, catalytic application, and synthetic transformations, further demonstrated the potential utility of this method. Notably, the remarkable chiral recognition ability of the products, along with the CPL activities offers significant opportunities for the development of chiral functional materials. Furthermore, the catalytic synthesis of diverse inherently chiral frameworks, and their potential applications are actively undergoing in our laboratory.

Methods

General procedure for the synthesis of compounds 3

An oven dried schleck tube charged with magnetic stirrer added 1 (0.1 mmol), Co(OAc)2·4H2O (0.01 mmol, 10 mol%), L2 (0.015 mmol, 15 mol%), NaOPiv·H2O (0.2 mmol, 2.0 equiv) with subsequent addition of fluorobenzene (1 mL) as solvent. To this reaction mixture, 2 (0.2 mmol, 2 equiv) was added under O2. Then, the reaction system was stirred at 80 °C for 8 h. After the reaction was completed, the reaction mixture was quenched with NaHCO3 saturated solution and extracted with CH2Cl2. The combined organic layer extracts were washed with brine, dried over Na2SO4, and concentrated under reduced pressure, and purified on silica gel chromatography (petroleum ether/ethyl acetate = 1:3) to afford the corresponding products.

Supplementary information

Supplementary Information

Peer Review File

Source data

Source Data

Supplementary information

The online version contains supplementary material available at 10.1038/s41467-024-52133-8.

Acknowledgements

We thank for the support of the National Natural Science Foundation of China (22271260 to J.-L.N.), Key Projects of the Joint Fund for Science and Technology of Henan Province (232301420007 to J.-L.N.), Excellent Youth Foundation of Henan Scientific Committee (242300421033 to J.-L.N.), and Postdoctoral Foundation of Henan Province (HN2024006 to D.Y.).

Author contributions

J.-L.N. and D.Y. conceived the concept and prepared the manuscript. T.L. and Y.Z. conducted the experiments and analyzed the data. M.-P.S. and C.D. provided revisions. All the authors participated in the discussion and preparation of the manuscript. J.-L.N. and D.Y. directed the project.

Peer review

Peer review information

Nature Communications thanks Ponneri C Ravikumar and the other anonymous reviewer(s) for their contribution to the peer review of this work. A peer review file is available.

Data availability

The X-ray crystallographic coordinates for the structure reported in this study have been deposited at the Cambridge Crystallographic Data Center (CCDC), under deposition number 2328817 (for 3ac). These data can be obtained free of charge from The Cambridge Crystallographic Data Center via www.ccdc.cam.ac.uk/data_request/cif. Data relating to the experimental procedures, optimization studies, and characterization of the new compounds are in Supplementary Information. Source data (for Supplementary Figs. 6–9, 14, 15) are provided with this paper. All other data are available from the corresponding authors upon request. Source data are provided in this paper.

Competing interests

The authors declare no competing interests.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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References

1. Böhmer V Kraft D Tabatabai M Inherently chiral calixarenes J. Inclusion Phenom. Mol. Recognit. Chem. 1994 19 17 39 10.1007/BF00708972
Böhmer, V., Kraft, D. & Tabatabai, M. Inherently chiral calixarenes. J. Inclusion Phenom. Mol. Recognit. Chem. 19, 17–39 (1994).10.1007/BF00708972
2. Dalla Cort A Mandolini L Pasquini C Schiaffino L “Inherent chirality” and curvature New. J. Chem. 2004 28 1198 1199 10.1039/B404388J
Dalla Cort, A., Mandolini, L., Pasquini, C. & Schiaffino, L. “Inherent chirality” and curvature. New. J. Chem. 28, 1198–1199 (2004).10.1039/B404388J
3. Szumna A Inherently chiral concave molecules—from synthesis to applications Chem. Soc. Rev. 2010 39 4274 4285 10.1039/b919527k 20882239
Szumna, A. Inherently chiral concave molecules—from synthesis to applications. Chem. Soc. Rev. 39, 4274–4285 (2010).20882239 10.1039/b919527k
4. McIldowie MJ Ogden MI A brief review of Cn-symmetric calixarenes and resorcinarenes Supramol. Chem. 2010 22 13 39 10.1080/10610270902980663
McIldowie, M. J. & Ogden, M. I. A brief review of Cn-symmetric calixarenes and resorcinarenes. Supramol. Chem. 22, 13–39 (2010).10.1080/10610270902980663
5. Han J-W Peng X-S Wong HNC Synthesis of tetraphenylene derivatives and their recent advances Natl. Sci. Rev. 2017 4 892 916 10.1093/nsr/nwx122
Han, J.-W., Peng, X.-S. & Wong, H. N. C. Synthesis of tetraphenylene derivatives and their recent advances. Natl. Sci. Rev. 4, 892–916 (2017).10.1093/nsr/nwx122
6. Zhou H Ao Y-F Wang D-X Wang Q-Q Inherently chiral cages via hierarchical desymmetrization J. Am. Chem. Soc. 2022 144 16767 16772 10.1021/jacs.2c08591 36070570
Zhou, H., Ao, Y.-F., Wang, D.-X. & Wang, Q.-Q. Inherently chiral cages via hierarchical desymmetrization. J. Am. Chem. Soc. 144, 16767–16772 (2022).36070570 10.1021/jacs.2c08591
7. Tang M Yang X Catalytic enantioselective synthesis of inherently chiral molecules: recent advances Eur. J. Org. Chem. 2023 26 e202300738 10.1002/ejoc.202300738
Tang, M. & Yang, X. Catalytic enantioselective synthesis of inherently chiral molecules: recent advances. Eur. J. Org. Chem. 26, e202300738 (2023).10.1002/ejoc.202300738
8. Luo Y Inherently chiral 6,7diphenyldibenzo[e,g][1,4]diazocine: enantioselective synthesis and application as a ligand platform CCS Chem. 2023 5 982 993 10.31635/ccschem.022.202201901
Luo, Y. et al. Inherently chiral 6,7diphenyldibenzo[e,g][1,4]diazocine: enantioselective synthesis and application as a ligand platform. CCS Chem. 5, 982–993 (2023).10.31635/ccschem.022.202201901
9. Luo J Zheng Q Chen C Huang Z Progress in inherently chiral calixarenes Prog. Chem. 2006 18 897 906
Luo, J., Zheng, Q., Chen, C. & Huang, Z. Progress in inherently chiral calixarenes. Prog. Chem. 18, 897–906 (2006).
10. Li S-Y Xu Y-W Liu J-M Su C-Y Inherently chiral calixarenes: synthesis, optical resolution, chiral recognition and asymmetric catalysis Int. J. Mol. Sci. 2011 12 429 455 10.3390/ijms12010429 21339996
Li, S.-Y., Xu, Y.-W., Liu, J.-M. & Su, C.-Y. Inherently chiral calixarenes: synthesis, optical resolution, chiral recognition and asymmetric catalysis. Int. J. Mol. Sci. 12, 429–455 (2011).21339996 10.3390/ijms12010429
11. Wang M-X Nitrogen and oxygen bridged calixaromatics: synthesis, structure, functionalization, and molecular recognition Acc. Chem. Res. 2012 45 182 195 10.1021/ar200108c 21834499
Wang, M.-X. Nitrogen and oxygen bridged calixaromatics: synthesis, structure, functionalization, and molecular recognition. Acc. Chem. Res. 45, 182–195 (2012).21834499 10.1021/ar200108c
12. Nimse SB Kim T Biological applications of functionalized calixarenes Chem. Soc. Rev. 2013 42 366 386 10.1039/C2CS35233H 23032718
Nimse, S. B. & Kim, T. Biological applications of functionalized calixarenes. Chem. Soc. Rev. 42, 366–386 (2013).23032718 10.1039/C2CS35233H
13. Guo D-S Liu Y Supramolecular chemistry of p-sulfonatocalix[n]arenes and its biological applications Acc. Chem. Res. 2014 47 1925 1934 10.1021/ar500009g 24666259
Guo, D.-S. & Liu, Y. Supramolecular chemistry of p-sulfonatocalix[n]arenes and its biological applications. Acc. Chem. Res. 47, 1925–1934 (2014).24666259 10.1021/ar500009g
14. Liu M Zhang L Wang T Supramolecular chirality in self-assembled systems Chem. Rev. 2015 115 7304 7397 10.1021/cr500671p 26189453
Liu, M., Zhang, L. & Wang, T. Supramolecular chirality in self-assembled systems. Chem. Rev. 115, 7304–7397 (2015).26189453 10.1021/cr500671p
15. Arnott GE Inherently chiral calixarenes: synthesis and applications Chem. -Eur. J. 2018 24 1744 1754 10.1002/chem.201703367 28809457
Arnott, G. E. Inherently chiral calixarenes: synthesis and applications. Chem. -Eur. J. 24, 1744–1754 (2018).28809457 10.1002/chem.201703367
16. Kumar R Revisiting fluorescent calixarenes: from molecular sensors to smart materials Chem. Rev., 2019 119 9657 9721 10.1021/acs.chemrev.8b00605 31306015
Kumar, R. et al. Revisiting fluorescent calixarenes: from molecular sensors to smart materials. Chem. Rev., 119, 9657–9721 (2019).31306015 10.1021/acs.chemrev.8b00605
17. Lhoták P Direct meta substitution of calix[4]arenes Org. Biomol. Chem. 2022 20 7377 7390 10.1039/D2OB01437H 36083220
Lhoták, P. Direct meta substitution of calix[4]arenes. Org. Biomol. Chem. 20, 7377–7390 (2022).36083220 10.1039/D2OB01437H
18. Durmaz M Alpaydin S Sirit A Yilmaz M Enantiomeric recognition of amino acid derivatives by chiral Schiff bases of calix[4]arene Tetrahedron: Asymmetry 2007 18 900 905 10.1016/j.tetasy.2007.04.001
Durmaz, M., Alpaydin, S., Sirit, A. & Yilmaz, M. Enantiomeric recognition of amino acid derivatives by chiral Schiff bases of calix[4]arene. Tetrahedron: Asymmetry 18, 900–905 (2007).10.1016/j.tetasy.2007.04.001
19. Xu Z-X Li G-K Chen C-F Huang Z-T Inherently chiral calix[4]arene-based bifunctional organocatalysts for enantioselective aldol reactions Tetrahedron 2008 64 8668 8675 10.1016/j.tet.2008.07.001
Xu, Z.-X., Li, G.-K., Chen, C.-F. & Huang, Z.-T. Inherently chiral calix[4]arene-based bifunctional organocatalysts for enantioselective aldol reactions. Tetrahedron 64, 8668–8675 (2008).10.1016/j.tet.2008.07.001
20. Shirakawa S Kimura T Murata SI Shimizu S Synthesis and resolution of a multifunctional inherently chiral calix[4]arene with an ABCD substitution pattern at the wide rim: the effect of a multifunctional structure in the organocatalyst on enantioselectivity in asymmetric reactions J. Org. Chem. 2009 74 1288 1296 10.1021/jo8024412 19099418
Shirakawa, S., Kimura, T., Murata, S. I. & Shimizu, S. Synthesis and resolution of a multifunctional inherently chiral calix[4]arene with an ABCD substitution pattern at the wide rim: the effect of a multifunctional structure in the organocatalyst on enantioselectivity in asymmetric reactions. J. Org. Chem. 74, 1288–1296 (2009).19099418 10.1021/jo8024412
21. Nandi P Solovyov A Okrut A Katz A AlIII-calix[4]arene catalysts for asymmetric Meerwein-Ponndorf-Verley reduction ACS Catal. 2014 4 2492 2495 10.1021/cs5001976
Nandi, P., Solovyov, A., Okrut, A. & Katz, A. AlIII-calix[4]arene catalysts for asymmetric Meerwein-Ponndorf-Verley reduction. ACS Catal. 4, 2492–2495 (2014).10.1021/cs5001976
22. Chen JH Wang, M. X. Highly strained oxygen‐doped chiral molecular belts of the zigzag‐type with strong circularly polarized luminescence Angew. Chem. Int. Ed. 2023 62 e202301782 10.1002/anie.202301782
Chen, J. H. et al. Wang, M. X. Highly strained oxygen‐doped chiral molecular belts of the zigzag‐type with strong circularly polarized luminescence. Angew. Chem. Int. Ed. 62, e202301782 (2023).10.1002/anie.202301782
23. Zhu W Cheng Y Tong Shuo Wang M-X Synthesis of functionalized ABAC- and ABCD- type inherently chiral heteracalix[4]aromatics Org. Lett. 2013 25 5105 5110 10.1021/acs.orglett.3c01830
Zhu, W., Cheng, Y., Tong, Shuo & Wang, M.-X. Synthesis of functionalized ABAC- and ABCD- type inherently chiral heteracalix[4]aromatics. Org. Lett. 25, 5105–5110 (2013).10.1021/acs.orglett.3c01830
24. Middel O The first lateral functionalization of calix[4]arenes by a homologous anionic ortho-fries rearrangement J. Org. Chem. 2000 65 667 675 10.1021/jo990976y
Middel, O. et al. The first lateral functionalization of calix[4]arenes by a homologous anionic ortho-fries rearrangement. J. Org. Chem. 65, 667–675 (2000).10.1021/jo990976y
25. Cao Y-D Preparation of both antipodes of enantiopure inherently chiral calix[4]crowns J. Org. Chem. 2004 69 206 208 10.1021/jo0354185 14703401
Cao, Y.-D. et al. Preparation of both antipodes of enantiopure inherently chiral calix[4]crowns. J. Org. Chem. 69, 206–208 (2004).14703401 10.1021/jo0354185
26. Luo J Zheng Q-Y Chen C-F Huang Z-T Facile synthesis and optical resolution of inherently chiral fluorescent calix[4]crowns: enantioselective recognition towards chiral leucinol Tetrahedron 2005 61 8517 8528 10.1016/j.tet.2005.06.015
Luo, J., Zheng, Q.-Y., Chen, C.-F. & Huang, Z.-T. Facile synthesis and optical resolution of inherently chiral fluorescent calix[4]crowns: enantioselective recognition towards chiral leucinol. Tetrahedron 61, 8517–8528 (2005).10.1016/j.tet.2005.06.015
27. Miao R Zheng Q-Y Chen C-F Huang Z-T Efficient syntheses and resolutions of inherently chiral calix[4]quinolines in the cone and partial-cone conformation J. Org. Chem. 2005 70 7662 7671 10.1021/jo050980b 16149797
Miao, R., Zheng, Q.-Y., Chen, C.-F. & Huang, Z.-T. Efficient syntheses and resolutions of inherently chiral calix[4]quinolines in the cone and partial-cone conformation. J. Org. Chem. 70, 7662–7671 (2005).16149797 10.1021/jo050980b
28. Luo J Zheng Q-Y Chen C-F Huang Z-T Synthesis and optical resolution of a series of inherently chiral calix[4]crowns with cone and partial cone conformations Chem. -Eur. J. 2005 11 5917 5928 10.1002/chem.200500272 15973749
Luo, J., Zheng, Q.-Y., Chen, C.-F. & Huang, Z.-T. Synthesis and optical resolution of a series of inherently chiral calix[4]crowns with cone and partial cone conformations. Chem. -Eur. J. 11, 5917–5928 (2005).15973749 10.1002/chem.200500272
29. Amato ME Novel chiral (Salen)MnIII complexes containing a calix[4]arene unit as catalysts for enantioselective epoxidation reactions of (Z)-aryl alkenes Eur. J. Org. Chem. 2005 16 3562 3570 10.1002/ejoc.200500138
Amato, M. E. et al. Novel chiral (Salen)MnIII complexes containing a calix[4]arene unit as catalysts for enantioselective epoxidation reactions of (Z)-aryl alkenes. Eur. J. Org. Chem. 16, 3562–3570 (2005).10.1002/ejoc.200500138
30. Yakovenko AV Diastereoselective lower rim (1S)-camphorsulfonylation as the shortest way to the inherently chiral calix[4]arene Org. Lett. 2007 9 1183 1185 10.1021/ol0628513 17323958
Yakovenko, A. V. et al. Diastereoselective lower rim (1S)-camphorsulfonylation as the shortest way to the inherently chiral calix[4]arene. Org. Lett. 9, 1183–1185 (2007).17323958 10.1021/ol0628513
31. Shirakawa S Moriyama A Shimizu S Design of a novel inherently chiral calix[4]arene for chiral molecular recognition Org. Lett. 2007 9 3117 3119 10.1021/ol071249p 17616144
Shirakawa, S., Moriyama, A. & Shimizu, S. Design of a novel inherently chiral calix[4]arene for chiral molecular recognition. Org. Lett. 9, 3117–3119 (2007).17616144 10.1021/ol071249p
32. Barton OG Neumann B Stammler H-G Mattay J Intramolecular direct arylation in an A,C-functionalized calix[4]arene Org. Biomol. Chem. 2008 6 104 111 10.1039/B713357J 18075654
Barton, O. G., Neumann, B., Stammler, H.-G. & Mattay, J. Intramolecular direct arylation in an A,C-functionalized calix[4]arene. Org. Biomol. Chem. 6, 104–111 (2008).18075654 10.1039/B713357J
33. Xu Z Zhang C Huang Z Chen C Efficient synthesis and resolution of meta-substituted inherently chiral aminocalix[4]arene derivatives Chin Sci. Bull. 2010 55 2859 2869 10.1007/s11434-010-3121-8
Xu, Z., Zhang, C., Huang, Z. & Chen, C. Efficient synthesis and resolution of meta-substituted inherently chiral aminocalix[4]arene derivatives Chin. Sci. Bull. 55, 2859–2869 (2010).10.1007/s11434-010-3121-8
34. Ciaccia M One-shot preparation of an inherently chiral trifunctional calix[4]arene from an easily available cone-triformylcalix[4]arene Org. Biomol. Chem. 2013 11 3642 3648 10.1039/c3ob40355f 23598888
Ciaccia, M. et al. One-shot preparation of an inherently chiral trifunctional calix[4]arene from an easily available cone-triformylcalix[4]arene. Org. Biomol. Chem. 11, 3642–3648 (2013).23598888 10.1039/c3ob40355f
35. Wang J-H Chen Y-C Zheng Y-S Shen C-H Selective nitration of calix[4]arenes that easily gave inherently chiral calix[4]arenes J. Inclusion Phenom. Macrocyclic Chem. 2014 80 449 455 10.1007/s10847-014-0413-7
Wang, J.-H., Chen, Y.-C., Zheng, Y.-S. & Shen, C.-H. Selective nitration of calix[4]arenes that easily gave inherently chiral calix[4]arenes. J. Inclusion Phenom. Macrocyclic Chem. 80, 449–455 (2014).10.1007/s10847-014-0413-7
36. Rosa MD Nucleophilic functionalization of the calix[6]arene para- and meta-position via p-bromodienone route J. Org. Chem. 2015 80 7295 7300 10.1021/acs.joc.5b00978 26083470
Rosa, M. D. et al. Nucleophilic functionalization of the calix[6]arene para- and meta-position via p-bromodienone route. J. Org. Chem. 80, 7295–7300 (2015).26083470 10.1021/acs.joc.5b00978
37. Slavík P Synthesis of inherently chiral calixarenes via direct mercuration of the partial cone conformation Chem. Commun. 2016 52 2366 2369 10.1039/C5CC09388K
Slavík, P. et al. Synthesis of inherently chiral calixarenes via direct mercuration of the partial cone conformation. Chem. Commun. 52, 2366–2369 (2016).10.1039/C5CC09388K
38. An F-J Bridging chiral calix[4]arenes: description, optical resolution, and absolute configuration determination Eur. J. Org. Chem. 2016 5 1012 1016 10.1002/ejoc.201501467
An, F.-J. et al. Bridging chiral calix[4]arenes: description, optical resolution, and absolute configuration determination. Eur. J. Org. Chem. 5, 1012–1016 (2016).10.1002/ejoc.201501467
39. Zhang W-Z Calix[4]arenes with combined axial chirality and inherent chirality: synthesis, absolute configuration and chiral recognition ChemistrySelect 2016 1 2486 2491 10.1002/slct.201600709
Zhang, W.-Z. et al. Calix[4]arenes with combined axial chirality and inherent chirality: synthesis, absolute configuration and chiral recognition. ChemistrySelect 1, 2486–2491 (2016).10.1002/slct.201600709
40. Böhmer, V., Merkel L. & Kunz, U. Asymmetrically-substituted calix(4)arenes. J. Chem. Soc., Chem. Commun. 896–897 (1987).
41. Arnecke R Böhmer V Paulus EF Vogt W Regioselective formation of dissymmetric resorcarene derivatives with C4-symmetry J. Am. Chem. Soc. 1995 117 3286 3287 10.1021/ja00116a039
Arnecke, R., Böhmer, V., Paulus, E. F. & Vogt, W. Regioselective formation of dissymmetric resorcarene derivatives with C4-symmetry. J. Am. Chem. Soc. 117, 3286–3287 (1995).10.1021/ja00116a039
42. Li J-T Synthesis, resolution, structure, and racemization of inherently chiral 1,3-alternate azacalix[4]pyrimidines: quantification of conformation mobility J. Org. Chem. 2014 79 2178 2188 10.1021/jo500054v 24512534
Li, J.-T. et al. Synthesis, resolution, structure, and racemization of inherently chiral 1,3-alternate azacalix[4]pyrimidines: quantification of conformation mobility. J. Org. Chem. 79, 2178–2188 (2014).24512534 10.1021/jo500054v
43. Zhang, W.-Z. et al. Inherently chiral calix[5]arenes incorporating an axially chiral binaphthyl moiety: synthesis, structures and chiral recognition. Eur. J. Org. Chem. 2015, 765–774 (2015).
44. Xu Z-X A new approach to enantiopure inherently chiral calix[4]arenes: determination of their absolute configurations Org. Lett. 2007 9 4447 4450 10.1021/ol701714q 17894502
Xu, Z.-X. et al. A new approach to enantiopure inherently chiral calix[4]arenes: determination of their absolute configurations. Org. Lett. 9, 4447–4450 (2007).17894502 10.1021/ol701714q
45. Xu Z-X Effective nonenzymatic kinetic resolution of racemic m-nitro-substituted inherently chiral aminocalix[4]arenes Org. Lett. 2008 10 477 479 10.1021/ol702884u 18184000
Xu, Z.-X. et al. Effective nonenzymatic kinetic resolution of racemic m-nitro-substituted inherently chiral aminocalix[4]arenes. Org. Lett. 10, 477–479 (2008).18184000 10.1021/ol702884u
46. Herbert SA Arnott GE An asymmetric ortholithiation approach to inherently chiral calix[4]arenes Org. Lett. 2009 11 4986 4989 10.1021/ol902238p 19813751
Herbert, S. A. & Arnott, G. E. An asymmetric ortholithiation approach to inherently chiral calix[4]arenes. Org. Lett. 11, 4986–4989 (2009).19813751 10.1021/ol902238p
47. Holub J Calix[4]arenes with intramolecularly bridged meta positions prepared via Pd-catalysed double C–H activation Chem. Commun. 2013 49 2798 2800 10.1039/c3cc40655e
Holub, J. et al. Calix[4]arenes with intramolecularly bridged meta positions prepared via Pd-catalysed double C–H activation. Chem. Commun. 49, 2798–2800 (2013).10.1039/c3cc40655e
48. Herbert SA Van Laeren LJ Castell DC Arnott GE Inherently chiral calix[4]arenes via oxazoline directed ortholithiation: synthesis and probe of chiral space Beilstein J. Org. Chem. 2014 10 2751 2755 10.3762/bjoc.10.291 25550740
Herbert, S. A., Van Laeren, L. J., Castell, D. C. & Arnott, G. E. Inherently chiral calix[4]arenes via oxazoline directed ortholithiation: synthesis and probe of chiral space. Beilstein J. Org. Chem. 10, 2751–2755 (2014).25550740 10.3762/bjoc.10.291
49. Castell DC Lesotho N Nikolayenko VI Arnott GE Inherently chiral calix[4]arenes: a chiral sulfoxide as an ortholithiation director Eur. J. Org. Chem. 2017 29 4328 4333 10.1002/ejoc.201700701
Castell, D. C., Lesotho, N., Nikolayenko, V. I. & Arnott, G. E. Inherently chiral calix[4]arenes: a chiral sulfoxide as an ortholithiation director. Eur. J. Org. Chem. 29, 4328–4333 (2017).10.1002/ejoc.201700701
50. Hodson L Facile synthesis of a C4-symmetrical inherently chiral calix[4]arene Chem. Commun. 2021 57 11045 11048 10.1039/D1CC04607A
Hodson, L. et al. Facile synthesis of a C4-symmetrical inherently chiral calix[4]arene. Chem. Commun. 57, 11045–11048 (2021).10.1039/D1CC04607A
51. Browne JK Enzymatic synthesis of nonracemic inherently chiral calix[4]arenes by lipase-catalysed transesterification Tetrahedron Lett. 1998 39 1787 1790 10.1016/S0040-4039(97)10865-6
Browne, J. K. et al. Enzymatic synthesis of nonracemic inherently chiral calix[4]arenes by lipase-catalysed transesterification. Tetrahedron Lett. 39, 1787–1790 (1998).10.1016/S0040-4039(97)10865-6
52. Giovanardi G Gold(i)-catalysed hydroarylations of alkynes for the synthesis of inherently chiral calix[4]arenes Org. Biomol. Chem. 2023 21 4072 4083 10.1039/D3OB00603D 37128860
Giovanardi, G. et al. Gold(i)-catalysed hydroarylations of alkynes for the synthesis of inherently chiral calix[4]arenes. Org. Biomol. Chem. 21, 4072–4083 (2023).37128860 10.1039/D3OB00603D
53. Ishibashi K Tsue H Takahashi H Tamura R Azacalix[4]arene tetramethyl ether with inherent chirality generated by substitution on the nitrogen bridges Tetrahedron: Asymmetry 2009 20 375 380 10.1016/j.tetasy.2009.01.017
Ishibashi, K., Tsue, H., Takahashi, H. & Tamura, R. Azacalix[4]arene tetramethyl ether with inherent chirality generated by substitution on the nitrogen bridges. Tetrahedron: Asymmetry 20, 375–380 (2009).10.1016/j.tetasy.2009.01.017
54. Tong S Catalytic enantioselective synthesis and switchable chiroptical property of inherently chiral macrocycles J. Am. Chem. Soc. 2020 142 14432 14436 10.1021/jacs.0c05369 32786737
Tong, S. et al. Catalytic enantioselective synthesis and switchable chiroptical property of inherently chiral macrocycles. J. Am. Chem. Soc. 142, 14432–14436 (2020).32786737 10.1021/jacs.0c05369
55. Zhang YZ Enantioselective synthesis of inherently chiral calix[4]arenes via palladium-catalyzed asymmetric intramolecular C-H arylations J. Am. Chem. Soc. 2022 144 22858 22864 10.1021/jacs.2c10606 36480794
Zhang, Y. Z. et al. Enantioselective synthesis of inherently chiral calix[4]arenes via palladium-catalyzed asymmetric intramolecular C-H arylations. J. Am. Chem. Soc. 144, 22858–22864 (2022).36480794 10.1021/jacs.2c10606
56. Zhang X Tong S Zhu J Wang M-X Inherently chiral calixarenes by a catalytic enantioselective desymmetrizing cross-dehydrogenative coupling Chem. Sci. 2023 14 827 832 10.1039/D2SC06234H 36755707
Zhang, X., Tong, S., Zhu, J. & Wang, M.-X. Inherently chiral calixarenes by a catalytic enantioselective desymmetrizing cross-dehydrogenative coupling. Chem. Sci. 14, 827–832 (2023).36755707 10.1039/D2SC06234H
57. Moselage M Li J Ackermann L Cobalt-catalyzed C-H activation ACS Catal. 2015 6 498 525 10.1021/acscatal.5b02344
Moselage, M., Li, J. & Ackermann, L. Cobalt-catalyzed C-H activation. ACS Catal. 6, 498–525 (2015).10.1021/acscatal.5b02344
58. Kommagalla Y Chatani N Cobalt(II)-catalyzed C-H functionalization using an N,N′-bidentate directing group Coord. Chem. Rev. 2017 350 117 135 10.1016/j.ccr.2017.06.018
Kommagalla, Y. & Chatani, N. Cobalt(II)-catalyzed C-H functionalization using an N,N′-bidentate directing group. Coord. Chem. Rev. 350, 117–135 (2017).10.1016/j.ccr.2017.06.018
59. Woźniak Ł Cramer N Enantioselective C-H bond functionalizations by 3d transition metal catalysts Trends Chem. 2019 1 471 484 10.1016/j.trechm.2019.03.013
Woźniak, Ł. & Cramer, N. Enantioselective C-H bond functionalizations by 3d transition metal catalysts. Trends Chem. 1, 471–484 (2019).10.1016/j.trechm.2019.03.013
60. Loup J Enantioselective C−H activation with earth-abundant 3d transition metals Angew. Chem. Int. Ed. 2019 58 12803 12818 10.1002/anie.201904214
Loup, J. et al. Enantioselective C−H activation with earth-abundant 3d transition metals. Angew. Chem. Int. Ed. 58, 12803–12818 (2019).10.1002/anie.201904214
61. Gandeepan P 3d Transition metals for C-H activation Chem. Rev. 2019 119 2192 2452 10.1021/acs.chemrev.8b00507 30480438
Gandeepan, P. et al. 3d Transition metals for C-H activation. Chem. Rev. 119, 2192–2452 (2019).30480438 10.1021/acs.chemrev.8b00507
62. Mandal R Garai B Sundararaju B Weak-coordination in C-H bond functionalizations catalyzed by 3d metals ACS Catal. 2022 12 3452 3506 10.1021/acscatal.1c05267
Mandal, R., Garai, B. & Sundararaju, B. Weak-coordination in C-H bond functionalizations catalyzed by 3d metals. ACS Catal. 12, 3452–3506 (2022).10.1021/acscatal.1c05267
63. Zheng Y Zheng C Gu Q You S-L Enantioselective C-H functionalization reactions enabled by cobalt catalysis Chem Catal. 2022 2 2965 2985 10.1016/j.checat.2022.08.020
Zheng, Y., Zheng, C., Gu, Q. & You, S.-L. Enantioselective C-H functionalization reactions enabled by cobalt catalysis. Chem Catal. 2, 2965–2985 (2022).10.1016/j.checat.2022.08.020
64. Bringmann G Atroposelective synthesis of axially chiral biaryl compounds Angew. Chem. Int. Ed. 2005 44 5384 5427 10.1002/anie.200462661
Bringmann, G. et al. Atroposelective synthesis of axially chiral biaryl compounds. Angew. Chem. Int. Ed. 44, 5384–5427 (2005).10.1002/anie.200462661
65. Wencel-Delord J Panossian A Leroux FR Colobert F Recent advances and new concepts for the synthesis of axially stereoenriched biaryls Chem. Soc. Rev. 2015 44 3418 3430 10.1039/C5CS00012B 25904287
Wencel-Delord, J., Panossian, A., Leroux, F. R. & Colobert, F. Recent advances and new concepts for the synthesis of axially stereoenriched biaryls. Chem. Soc. Rev. 44, 3418–3430 (2015).25904287 10.1039/C5CS00012B
66. Kumarasamy E Raghunathan R Sibi MP Sivaguru J Nonbiaryl and heterobiaryl atropisomers: molecular templates with promise for atropselective chemical transformations Chem. Rev. 2015 115 11239 11300 10.1021/acs.chemrev.5b00136 26414162
Kumarasamy, E., Raghunathan, R., Sibi, M. P. & Sivaguru, J. Nonbiaryl and heterobiaryl atropisomers: molecular templates with promise for atropselective chemical transformations. Chem. Rev. 115, 11239–11300 (2015).26414162 10.1021/acs.chemrev.5b00136
67. Wang Y-B Tan B Construction of axially chiral compounds via asymmetric organocatalysis Acc. Chem. Res. 2018 51 534 547 10.1021/acs.accounts.7b00602 29419282
Wang, Y.-B. & Tan, B. Construction of axially chiral compounds via asymmetric organocatalysis. Acc. Chem. Res. 51, 534–547 (2018).29419282 10.1021/acs.accounts.7b00602
68. Metrano AJ Miller SJ Peptide-based catalysts reach the outer sphere through remote desymmetrization and atroposelectivity Acc. Chem. Res. 2019 52 199 215 10.1021/acs.accounts.8b00473 30525436
Metrano, A. J. & Miller, S. J. Peptide-based catalysts reach the outer sphere through remote desymmetrization and atroposelectivity. Acc. Chem. Res. 52, 199–215 (2019).30525436 10.1021/acs.accounts.8b00473
69. Liu Z-S Construction of axial chirality via palladium/chiral norbornene cooperative catalysis Nat. Catal. 2020 3 727 733 10.1038/s41929-020-0494-1
Liu, Z.-S. et al. Construction of axial chirality via palladium/chiral norbornene cooperative catalysis. Nat. Catal. 3, 727–733 (2020).10.1038/s41929-020-0494-1
70. Li Z Yu S Asymmetric synthesis of atropisomeric compounds with C-N chiral axis Sci. Sin. Chim. 2020 50 509 525 10.1360/SSC-2019-0168
Li, Z. & Yu, S. Asymmetric synthesis of atropisomeric compounds with C-N chiral axis. Sci. Sin. Chim. 50, 509–525 (2020).10.1360/SSC-2019-0168
71. Kitagawa O Chiral Pd-catalyzed enantioselective syntheses of various N-C axially chiral compounds and their synthetic applications Acc. Chem. Res. 2021 54 719 730 10.1021/acs.accounts.0c00767 33481580
Kitagawa, O. Chiral Pd-catalyzed enantioselective syntheses of various N-C axially chiral compounds and their synthetic applications. Acc. Chem. Res. 54, 719–730 (2021).33481580 10.1021/acs.accounts.0c00767
72. Zhang Z-X Zhai T-Y Ye L-W Synthesis of axially chiral compounds through catalytic asymmetric reactions of alkynes Chem Catal. 2021 1 1378 1412 10.1016/j.checat.2021.09.011
Zhang, Z.-X., Zhai, T.-Y. & Ye, L.-W. Synthesis of axially chiral compounds through catalytic asymmetric reactions of alkynes. Chem Catal. 1, 1378–1412 (2021).10.1016/j.checat.2021.09.011
73. Basilaia M Chen MH Secka J Gustafson JL Atropisomerism in the pharmaceutically relevant realm Acc. Chem. Res. 2022 55 2904 2919 10.1021/acs.accounts.2c00500 36153960
Basilaia, M., Chen, M. H., Secka, J. & Gustafson, J. L. Atropisomerism in the pharmaceutically relevant realm. Acc. Chem. Res. 55, 2904–2919 (2022).36153960 10.1021/acs.accounts.2c00500
74. Mei G-J Koay WL Guan C-Y Lu Y Atropisomers beyond the C–C axial chirality: advances in catalytic asymmetric synthesis Chem 2022 8 1 39 10.1016/j.chempr.2022.04.011
Mei, G.-J., Koay, W. L., Guan, C.-Y. & Lu, Y. Atropisomers beyond the C–C axial chirality: advances in catalytic asymmetric synthesis. Chem 8, 1–39 (2022).10.1016/j.chempr.2022.04.011
75. Carlsson AC Karlsson S Munday RH Tatton MR Approaches to synthesis and isolation of enantiomerically pure biologically active atropisomers Acc. Chem. Res. 2022 55 2938 2948 10.1021/acs.accounts.2c00513 36194144
Carlsson, A. C., Karlsson, S., Munday, R. H. & Tatton, M. R. Approaches to synthesis and isolation of enantiomerically pure biologically active atropisomers. Acc. Chem. Res. 55, 2938–2948 (2022).36194144 10.1021/acs.accounts.2c00513
76. Lu C-J Xu Q Feng J Liu R-R The asymmetric buchwald-hartwig amination reaction Angew. Chem. Int. Ed. 2023 62 e202216863 10.1002/anie.202216863
Lu, C.-J., Xu, Q., Feng, J. & Liu, R.-R. The asymmetric buchwald-hartwig amination reaction. Angew. Chem. Int. Ed. 62, e202216863 (2023).10.1002/anie.202216863
77. Liao G Zhou T Yao Q-J Shi B-F Recent advances in the synthesis of axially chiral biaryls via transition metal-catalysed asymmetric C–H functionalization Chem. Commun. 2019 55 8514 8523 10.1039/C9CC03967H
Liao, G., Zhou, T., Yao, Q.-J. & Shi, B.-F. Recent advances in the synthesis of axially chiral biaryls via transition metal-catalysed asymmetric C–H functionalization. Chem. Commun. 55, 8514–8523 (2019).10.1039/C9CC03967H
78. Liu C-X Synthesis of atropisomers by transition-metal-catalyzed asymmetric C–H functionalization reactions J. Am. Chem. Soc. 2021 143 14025 14040 10.1021/jacs.1c07635 34432467
Liu, C.-X. et al. Synthesis of atropisomers by transition-metal-catalyzed asymmetric C–H functionalization reactions. J. Am. Chem. Soc. 143, 14025–14040 (2021).34432467 10.1021/jacs.1c07635
79. Choppin S Wencel-Delord J Sulfoxide-directed or 3d-metal catalyzed c–h activation and hypervalent iodines as tools for atroposelective synthesis Acc. Chem. Res. 2023 56 189 202 10.1021/acs.accounts.2c00573 36705934
Choppin, S. & Wencel-Delord, J. Sulfoxide-directed or 3d-metal catalyzed c–h activation and hypervalent iodines as tools for atroposelective synthesis. Acc. Chem. Res. 56, 189–202 (2023).36705934 10.1021/acs.accounts.2c00573
80. Jacob N Cobalt-catalyzed enantioselective C–H arylation of indoles J. Am. Chem. Soc. 2022 144 798 806 10.1021/jacs.1c09889 35001624
Jacob, N. et al. Cobalt-catalyzed enantioselective C–H arylation of indoles. J. Am. Chem. Soc. 144, 798–806 (2022).35001624 10.1021/jacs.1c09889
81. Yin S-Y Enantioselective synthesis of N-N biaryl atropisomers through iridium(i)-catalyzed C-H alkylation with acrylates Angew. Chem. Int. Ed. 2023 62 e202305067 10.1002/anie.202305067
Yin, S.-Y. et al. Enantioselective synthesis of N-N biaryl atropisomers through iridium(i)-catalyzed C-H alkylation with acrylates. Angew. Chem. Int. Ed. 62, e202305067 (2023).10.1002/anie.202305067
82. Wang Y Rhodium-catalyzed enantioselective and diastereodivergent access to diaxially chiral heterocycles Nat. Commun. 2023 14 4661 10.1038/s41467-023-39968-3 37537163
Wang, Y. et al. Rhodium-catalyzed enantioselective and diastereodivergent access to diaxially chiral heterocycles. Nat. Commun. 14, 4661 (2023).37537163 10.1038/s41467-023-39968-3
83. Si X-J Atroposelective isoquinolinone synthesis through cobalt-catalysed C−H activation and annulation Nat. Synth. 2022 1 709 718 10.1038/s44160-022-00114-4
Si, X.-J. et al. Atroposelective isoquinolinone synthesis through cobalt-catalysed C−H activation and annulation. Nat. Synth. 1, 709–718 (2022).10.1038/s44160-022-00114-4
84. Li T Cobalt-catalyzed atroposelective C−H activation/annulation to access N−N axially chiral frameworks Nat. Commun. 2023 14 5271 10.1038/s41467-023-40978-4 37644016
Li, T. et al. Cobalt-catalyzed atroposelective C−H activation/annulation to access N−N axially chiral frameworks. Nat. Commun. 14, 5271 (2023).37644016 10.1038/s41467-023-40978-4
85. Si X-J Cobalt-catalyzed enantioselective C−H/N−H annulation of aryl sulfonamides with allenes or alkynes: facile access to C–N axially chiral sultams Chem. Sci. 2023 14 7291 7303 10.1039/D3SC01787G 37416705
Si, X.-J. et al. Cobalt-catalyzed enantioselective C−H/N−H annulation of aryl sulfonamides with allenes or alkynes: facile access to C–N axially chiral sultams. Chem. Sci. 14, 7291–7303 (2023).37416705 10.1039/D3SC01787G
86. Wang X C–N Axially chiral heterobiaryl isoquinolinone skeletons construction via cobalt-catalyzed atroposelective C–H activation/annulation Org. Lett. 2023 25 6240 6245 10.1021/acs.orglett.3c01685 37595028
Wang, X. et al. C–N Axially chiral heterobiaryl isoquinolinone skeletons construction via cobalt-catalyzed atroposelective C–H activation/annulation. Org. Lett. 25, 6240–6245 (2023).37595028 10.1021/acs.orglett.3c01685
87. Zhang Y N, O-auxiliary enabled cobaltaelectro-catalyzed atroposelective C−H annulation ACS Catal. 2024 14 1 9 10.1021/acscatal.3c04853
Zhang, Y. et al. N, O-auxiliary enabled cobaltaelectro-catalyzed atroposelective C−H annulation. ACS Catal. 14, 1–9 (2024).10.1021/acscatal.3c04853
88. Wang B-J Single-step synthesis of atropisomers with vicinal C−C and C−N diaxes by cobalt-catalyzed atroposelective C–H annulation Angew. Chem. Int. Ed. 2022 61 e202208912 10.1002/anie.202208912
Wang, B.-J. et al. Single-step synthesis of atropisomers with vicinal C−C and C−N diaxes by cobalt-catalyzed atroposelective C–H annulation. Angew. Chem. Int. Ed. 61, e202208912 (2022).10.1002/anie.202208912
89. Wu Y-J Synthesis of axially chiral biaryls through cobalt(II)-catalyzed atroposelective C–H arylation Angew. Chem. Int. Ed. 2023 62 e202310004 10.1002/anie.202310004
Wu, Y.-J. et al. Synthesis of axially chiral biaryls through cobalt(II)-catalyzed atroposelective C–H arylation. Angew. Chem. Int. Ed. 62, e202310004 (2023).10.1002/anie.202310004
90. Von Münchow T Enantioselective electrochemical cobalt-catalyzed aryl C–H activation reactions Science 2023 379 1036 1042 10.1126/science.adg2866 36893225
Von Münchow, T. et al. Enantioselective electrochemical cobalt-catalyzed aryl C–H activation reactions. Science 379, 1036–1042 (2023).36893225 10.1126/science.adg2866
91. Lin Y von Münchow T Ackermann L Cobaltaelectro-catalyzed C–H annulation with allenes for atropochiral and P-stereogenic compounds: late-stage diversification and continuous flow scale-up ACS Catal. 2023 13 9713 9723 10.1021/acscatal.3c02072 38076330
Lin, Y., von Münchow, T. & Ackermann, L. Cobaltaelectro-catalyzed C–H annulation with allenes for atropochiral and P-stereogenic compounds: late-stage diversification and continuous flow scale-up. ACS Catal. 13, 9713–9723 (2023).38076330 10.1021/acscatal.3c02072
92. Bao X Rodriguez J Bonne D Enantioselective synthesis of atropisomers with multiple stereogenic axes Angew. Chem. Int. Ed. 2020 59 12623 12634 10.1002/anie.202002518
Bao, X., Rodriguez, J. & Bonne, D. Enantioselective synthesis of atropisomers with multiple stereogenic axes. Angew. Chem. Int. Ed. 59, 12623–12634 (2020).10.1002/anie.202002518
93. Ye F Xu Z Xu L-W The discovery of multifunctional chiral P ligands for the catalytic construction of quaternary carbon/silicon and multiple stereogenic centers Acc. Chem. Res. 2021 54 452 470 10.1021/acs.accounts.0c00740 33375791
Ye, F., Xu, Z. & Xu, L.-W. The discovery of multifunctional chiral P ligands for the catalytic construction of quaternary carbon/silicon and multiple stereogenic centers. Acc. Chem. Res. 54, 452–470 (2021).33375791 10.1021/acs.accounts.0c00740
94. Schmidt TA Sparr C Catalyst control over twofold and higher-order stereogenicity by atroposelective arene formation Acc. Chem. Res. 2021 54 2764 2774 10.1021/acs.accounts.1c00178 34056908
Schmidt, T. A. & Sparr, C. Catalyst control over twofold and higher-order stereogenicity by atroposelective arene formation. Acc. Chem. Res. 54, 2764–2774 (2021).34056908 10.1021/acs.accounts.1c00178
95. Bai X-F Cui Y-M Cao J Xu L-W Atropisomers with axial and point chirality: synthesis and applications Acc. Chem. Res. 2022 55 2545 2561 10.1021/acs.accounts.2c00417 36083117
Bai, X.-F., Cui, Y.-M., Cao, J. & Xu, L.-W. Atropisomers with axial and point chirality: synthesis and applications. Acc. Chem. Res. 55, 2545–2561 (2022).36083117 10.1021/acs.accounts.2c00417
96. Luc A Wencel-Delord J One reaction-double stereoinduction: C–H activation as a privileged route towards complex atropisomeric molecules Chem. Commun. 2023 59 8159 8167 10.1039/D3CC01328F
Luc, A. & Wencel-Delord, J. One reaction-double stereoinduction: C–H activation as a privileged route towards complex atropisomeric molecules. Chem. Commun. 59, 8159–8167 (2023).10.1039/D3CC01328F
97. Zhang H-H Li T-Z Liu S-J Shi F Catalytic asymmetric synthesis of atropisomers bearing multiple chiral elements: an emerging field Angew. Chem. Int. Ed. 2023 62 e202311053
Zhang, H.-H., Li, T.-Z., Liu, S.-J. & Shi, F. Catalytic asymmetric synthesis of atropisomers bearing multiple chiral elements: an emerging field. Angew. Chem. Int. Ed. 62, e202311053 (2023).
98. Moser D Schmidt TA Sparr C Diastereodivergent catalysis JACS Au 2023 3 2612 2630 10.1021/jacsau.3c00216 37885579
Moser, D., Schmidt, T. A. & Sparr, C. Diastereodivergent catalysis. JACS Au 3, 2612–2630 (2023).37885579 10.1021/jacsau.3c00216
99. Hao X-Q Copper-mediated direct aryloxylation of benzamides assisted by an N,O-bidentate directing group Org. Lett. 2014 16 1104 1107 10.1021/ol500166d 24502415
Hao, X.-Q. et al. Copper-mediated direct aryloxylation of benzamides assisted by an N,O-bidentate directing group. Org. Lett. 16, 1104–1107 (2014).24502415 10.1021/ol500166d
100. Zhang L-B Cobalt-catalyzed C(sp2)-H alkoxylation of aromatic and olefinic carboxamides Angew. Chem. Int. Ed. 2015 54 272 275 10.1002/anie.201409751
Zhang, L.-B. et al. Cobalt-catalyzed C(sp2)-H alkoxylation of aromatic and olefinic carboxamides. Angew. Chem. Int. Ed. 54, 272–275 (2015).10.1002/anie.201409751
101. Zhang L-B Cobalt(II)-catalyzed Csp2-H alkynylation/annulation with terminal alkynes: selective access to 3-methyleneisoindolin-1-one Angew. Chem. Int. Ed. 2015 54 10012 10015 10.1002/anie.201504962
Zhang, L.-B. et al. Cobalt(II)-catalyzed Csp2-H alkynylation/annulation with terminal alkynes: selective access to 3-methyleneisoindolin-1-one. Angew. Chem. Int. Ed. 54, 10012–10015 (2015).10.1002/anie.201504962
