Chiral Organic Cages with a Triple-Stranded Helical Structure Derived

Subscriber access provided by UNIVERSITY OF TOLEDO LIBRARIES

Communication

Chiral Organic Cages with A Triple-Stranded Helical Structure Derived from Helicene Abaid Ullah Malik, Fuwei Gan, Chengshuo Shen, Na Yu, Ruibin Wang, Jeanne Crassous, Mouhai Shu, and Huibin Qiu J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.7b13512 • Publication Date (Web): 09 Feb 2018 Downloaded from http://pubs.acs.org on February 9, 2018

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

Journal of the American Chemical Society is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 6 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Journal of the American Chemical Society

Chiral Organic Cages with A Triple-Stranded Helical Structure Derived from Helicene Abaid Ullah Malik,†,# Fuwei Gan,‡,# Chengshuo Shen,‡,* Na Yu,‡ Ruibin Wang,|| Jeanne Crassous,§ Mouhai Shu,†,* Huibin Qiu†,‡,* †

School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.

‡

School of Physical Science and Technology, ShanghaiTech University, Shanghai, 201210, China.

§

Institut des Sciences Chimiques de Rennes, UMR 6226, Campus de Beaulieu, CNRS-Université de Rennes 1, 35042 Rennes Cedex, France. ||

Instrumental Analysis Center, Shanghai Jiao Tong University, Shanghai, 200240, China.

Supporting Information Placeholder

ABSTRACT: We report the use of helicene with an intrinsic helical molecular structure to prepare covalent organic cages via imine condensation. The organic cages revealed a [3+2] type architecture containing a triple-stranded helical structure with three helicene units arranged in a propeller-like fashion and the framework integrally twisted. Such structural chirality was retained upon dissolution in organic solvents as indicated by a strong diastereotopy effect in proton NMR and unique Cotton effects in circular dichroism spectra. Further study on chiral adsorption showed that the chiral organic cages possess considerable enantioselectivity towards a series of aromatic racemates.

The creation of architectures beyond a simple molecule has emerged as a main topic in a wide range of 1 fields. In this context, organic cages have recently attracted much attention due to their unique hollow molecular structures and prominent applications in catal2 ysis, separation, sensing, gas storage, etc. The synthesis of organic cages, despite of a few cases using irre3 versible bond formation, normally involves reversible 4 linkage chemistries such as imine condensation, me5 6 tathesis, and boronic ester formation, to avoid dynamically trapped random conjunctions. On the other hand, the structure and function of organic cages highly rely on the chemistry and geometry of building 7 blocks. Up to now, the utilization of relatively complex molecules in cage synthesis remains a challenge and only a few systems have been reported which employed for example porphyrin or hemicarcerand deriv8 atives. Consequently, it is highly desirable to develop new molecular building blocks to further enrich the organic cage family.

Helicenes are a type of molecules possessing a nonplanar helical structure composed by ortho-fused aro9 matic rings (total number ≥ 4). Owing to their unique helical π-conjugated system, helicenes present compel10 ling chiroptical properties. The helical geometry together with the distinctive optical performance make helicene a promising candidate in asymmetric cataly11 12 13 sis, chiral recognition, chiroptical switches, circu14 larly polarized light devices, etc. Herein, we demonstrate a synthetic route to prepare covalent organic cages using ditopic aldehyde-substituted helicene derivatives as chiral building blocks. Covalent linking of three helicene molecules with two triaminefunctionalized vertices via imine condensation led to the formation of chiral organic cages with a novel triple helix structure. We also demonstrate the potential application of such chiral organic cages in the separation of chiral molecules utilizing the structural chirality derived from the aligned helicene units and the twisted framework. The cage construction started from the synthesis of enantiopure M- and P-4,13-diethynyl[6]helicene 1 via photocyclization, followed by chiral resolution by 15 HPLC (See Supporting Information for details). The enantiomers were further functionalized with iodosubstituted aldehyde 2 through Sonogashira coupling (Scheme 1), yielding precursors M-3 and P-3, respectively. X-ray diffraction of a single crystal of P-3 reveals 16 a ሬΔԦ geometry with six benzene rings orthogonally fused in a right-handed helical fashion and two benzaldehyde units pointing to opposite directions (Figure S3-2). Subsequently, commercially available tritopic amine unit tris(2-aminoethyl)amine 4 was reacted with 3 in a 2:3 molar ratio under catalytic amount of trifluoroacetic acid in dichloromethane. The imine condensation between the amine and aldehyde groups led

ACS Paragon Plus Environment

Journal of the American Chemical Society 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

to the formation of yellow solids in a yield of 67-69%, which were dissolvable (>1 mg/mL) in organic solvents such as CH2Cl2, CHCl3, and diethyl ether. Electrospray ionization mass spectrometry (ESI-MS) recorded well-resolved peaks at m/z = 1184.0593 and 1184.0559 for the materials derived from P- and Mhelicenes, respectively (Figures S2-18 and S2-19), indicating the formation of a [3+2] cage (calculated m/z = 1184.0542, z = 2) with two trisimide caps linked by three helicene units (Scheme 1). This was further verified by NMR spectra (Figures S2-7 to S2-13). The disappearance of the aldehyde signal at 9.95 ppm and the 1 emergence of the aldimine signal at 7.69 ppm in the H NMR spectrum confirmed the complete imine condensation (Figure S2-7). Besides, the absence of obviously 1 13 split or broadened signals in the H and C NMR spectra (Figures S2-7 and S2-8) eliminated the possibility of any polymeric products, and also indicated that cage 5 may possess a highly symmetric structure. Scheme 1. Synthetic route of organic cages using helicene derivatives as building blocks.

The absolute structure was subsequently resolved by X-ray crystallography. Pale-yellow single crystals were obtained by layering a methanol solution of amine 4 onto the dichloromethane solutions of M-3 or P-3 with catalytic amount of trifluoroacetic acid. Enantiopure cages 5 were thus synthesized in situ in a crystal form, and the crystals were quickly investigated by X-ray diffraction since they could easily effloresce. The visualized results revealed the presence of the expected [3+2] constitution of cage 5 with two amine moieties on the top and bottom, and connected by three helicene-based lateral arms. Taking M,M,M-5 for instance, the compound crystallized in a C2 space group with a large unit cell containing six cage molecules with two a nearly identical conformations, namely M,M,M-5 and b M,M,M-5 , in a ratio of 2:1 (Figure S3-6). Both two con-

Page 2 of 6

formations resolved a pseudo D3 symmetry with a C3 axis going through the center of two amine moieties and three C2 axes perpendicularly across the C3 axis and passing through the center of each helicene (Figure 1b). The crystal packing of P,P,P-5 was mirrorimage from that of M,M,M-5, and likewise, the unit cell a b contained 2/3 of P,P,P-5 and 1/3 of P,P,P-5 . By further scrutinizing the crystal structure, we found that the skeleton of 5 adopted a structurally chiral conformation where three lateral arms were twisted a b into a triple helix. In both M,M,M-5 and M,M,M-5 the ሬԦ propeller-like fashhelicene units were aligned in a Λ ion with the ends pointing inwards the cage cavity, forming a open cave that can be accessible from three directions (Figure 1a). Based on this propeller, the three lateral arms turned clockwise around 120° from bottom to top along the pseudo C3 axis, resulting in a left-handed triple helix. On the contrary, right-handed a b triple helix can be observed in P,P,P-5 and P,P,P-5 . Such structural chirality was thought to be derived from the intrinsic chiral feature of helicene (especially the large dihedral angle between two terminal aromatic rings).

a

Figure 1. (a) Crystal structures of organic cages M,M,M-5 a and P,P,P-5 (H atoms are omitted) (b) Schematic representations of M,M,M-5 and P,P,P-5 illustrating the D3 symmetry and the triple-stranded helical structure.

The aforementioned structural chirality was also de1 tected in solution. As indicated by H NMR spectroscopy (Figure S2-20), four sets of signals were found between 4.0 and 2.4 ppm, corresponding to the twelve CH2 groups adjacent to the N atoms. Due to the D3 symmetry, these twelve CH2 groups can be classified into two types of identical CH2 groups. Interestingly, each type of CH2 groups gave two sets of peaks, which


Page 3 of 6 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Journal of the American Chemical Society can be interpreted by a diastereotopy effect resulting from the structural chirality of the twisted organic cage framework. To confirm this, we prepared a singlestranded helicene derivative 6 (Figure 2, inset) analogous to one of the lateral arms of cage 5. The open termini of 6 eliminated the restricted helical conformation that existed in cage 5 and consequently, the protons of the corresponding CH2 in 6 revealed only two sets of signals (Figure S2-20). Therefore, it can be concluded that cage 5 retained its structural chirality in solution, with chirality transferring from the helicene units to the entire arms through integral twisting. Electronic circular dichroism (ECD) spectroscopy was further employed to investigate the chiral structure of cage 5 in solution. As shown in Figure 2, the M,M,M-5 and P,P,P-5 cages revealed mirror-image ECD spectra with very strong Cotton effects in the region between 230 and 450 nm. Notably, P,P,P-5 displayed a positive Cotton effect at 330 nm followed by a negative one at 242 nm with Δε values of +537 and −708 −1 −1 L·mol ·cm , respectively, which can be ascribed to the 17 characteristic nature of the P-helicene components. However, these Cotton effects appeared more structured than the simple and smooth signals presented in the P-6 analogue. Besides, P,P,P-5 showed a relatively strong negative Cotton effect around 365 nm (Δε = −181 −1 −1 L·mol ·cm ), which may be related to the twisting of the ethynyl conjugated arms in the helical cage framework (Figure 2, inset). While for P-6, the lack of structural restriction rendered the ethynyl conjugated arms more planar (without additional induced chirality caused by twisting, Figure 2, inset). Hence, the peak of the Cotton effect bathochromically shifted to a longer wavelength and the intensity dramatically decreased −1 −1 (Δε' = −45 L·mol ·cm at 380 nm in maximum). In contrast to the ECD performances, cage 5 showed significantly weaker absorption bands between 290 and 4 450 nm than for analogue 6 (Figure 2, ε = 6.2 × 10 −1 −1 4 −1 −1 L·mol ·cm for cage 5 vs ε' = 12.2 × 10 L·mol ·cm for 6 at 360 nm). This presumably also reflected the more extended π-conjugation in helicene P-6 than in the more rigid P,P,P-5. Previously, a few pioneering groups have demonstrated the use of chiral organic cages to separate chi18 ral molecules from the racemates. In our organic cage 5, three helicene units formed a propeller array with their helical arms pointing inwards and surrounding the cage cavity. This unique chiral environment, together with the triple-stranded helical skeleton, might enhance the enantioselectivity towards chiral molecules. As a demonstration, the racemates of 1phenylethylamine (7), 1-phenylethanol (8), 1,1'binaphthalene-2,2'-diol (9) (Table 1) were employed as the guest molecules and enantioselective adsorption experiments were conducted by treating the suspension of the enantiopure cage 5 (host) in isopropanol

solutions of 7-9, filtrating the host-guest systems and extracting the encapsulated guest molecules with diethyl ether and finally examining the enantiomeric excess (ee) by chiral HPLC (see Supporting Information for more details).

Figure 2. UV-vis and ECD spectra of M,M,M-5 (solid red lines) and P,P,P-5 (solid green lines) and their analogues M-6 (dash orange lines) and P-6 (dash blue lines) in CH2Cl2 (c = 2 −5 −1 × 10 mol·L ). The intensity of the UV-vis and ECD spectra of M-6 and P-6 were deliberately enhanced by three times (denoted by ε' and Δε', respectively) for a clearer comparison with cage 5 which possesses three helicene-derived lateral arms in one cage molecule.

Table 1. Data of Chiral Adsorption Experiments. Entry

Guest

1 2

7

3 4

8

5

OH OH

6 7 8

9 7

Host

ee

M,M,M-5

60% (S)

P,P,P-5

58% (R)

M,M,M-5

84% (S)

P,P,P-5

67% (R)

M,M,M-5

23% (S)

P,P,P-5

20% (R)

M-3 P-3

1% (S) 2% (R)

As shown in Table 1, cage M,M,M-5 preferentially recognized S-7 and S-8, thus resulting in ee's of 60% and 84%, respectively, which appeared to be promising in consideration of the relatively low ee's revealed by 18a,b other chiral cages. Similarly, P,P,P-5 showed enantioselectivity towards R-7 and R-8 with ee of 58% and 67%, respectively. The enantioselective adsorption of larger molecules such as 9 was less efficient probably due to the relatively compact cavity of 5, but still revealed ee values of over 20%. On the contrary, the enantiopure precursor 3 showed neglectable enantioselectivity towards 7. These results indicated that the enantioselective adsorption originates from the inte-



gral chiral structure and inner cavity of cage 5 (hostguest recognition), rather than the discrete helicene moieties. In conclusion, we have demonstrated the formation of chiral organic cage using helicene as the building block. The chiral cages exhibited a unique triplestranded helical architecture with three helicene units aligned in propeller shape. As indicated by the enantioselectivity towards aromatic racemates, these materials are of potential application in chiral separation and purification. Besides, the twisted cavity and the preintroduced hydroxyl groups would facilitate further utilization in asymmetric catalysis. The current work enriched the geometry and complexity of building blocks and would thus encourage more innovative access to functional organic cages.

ASSOCIATED CONTENT Supporting Information

The Supporting Information is available free of charge on the ACS Publications website. X-ray crystallographic data for P-1 (CIF) X-ray crystallographic data for P-3(CIF) X-ray crystallographic data for P,P,P-5 (CIF) X-ray crystallographic data for M,M,M-5 (CIF) Synthetic procedures and characterization data (NMR, ESI-MS, X-ray crystallography, UV-vis and ECD spectra) for all new compounds, and details for the chiral resolution experiments (PDF)

AUTHOR INFORMATION Corresponding Author

*E-mail: [email protected] *E-mail: [email protected]. *E-mail: [email protected]. ORCID

Huibin Qiu: 0000-0002-4699-6558 Mouhai Shu: 0000-0002-8556-7369 Chengshuo Shen: 0000-0003-2422-3922 Author Contributions #

These authors contributed equally.

Notes

The authors declare no competing financial interests.

ACKNOWLEDGMENT This work was supported by the National Natural Science Foundation of China (21271129, 21674062, U1632117, 21704063) and the Science and Technology Commission of Shanghai Municipality (16ZR1422600, 16PJ1406600, 17YF1412100, 17JC400700).

REFERENCES (1) (a) Furukawa, H.; Cordova, K. E.; O’Keeffe, M.; Yaghi, O. M. Science 2013, 341, 1230444. (b) Zhang, G.; Mastalerz, M.

Page 4 of 6

Chem. Soc. Rev. 2014, 43, 1934−1947. (c) Hasell, T.; Cooper, A. I. Nat. Rev. Mater. 2016, 1, 16053. (2) (a) Yoshizawa, M.; Tamura, M.; Fujita, M. Science, 2006, 312, 251−254. (b) Wang, B.; Côté, A. P.; Furukawa, H.; O’Keeffe, M.; Yaghi, O. M. Nature, 2008, 453, 207−211. (c) Mal, P.; Breiner, B.; Rissanen, K.; Nitschke, J. R. Science, 2009, 324, 1697−1699. (d) Badetti, E.; Wurst, K.; Licini, G.; Zonta, C. Chem. Eur. J. 2016, 22, 6515−6518. (3) (a) Zhang, C.; Chen, C.-F. J. Org. Chem. 2007, 72, 9339−9341. (b) Avellaneda, A.; Valente, P.; Burgun, A.; Evans, J. D.; Markwell-Heys, A. W.; Rankine, D.; Nielsen, D. J.; Hill, M. R.; Sumby, C. J.; Doonan, C. J. Angew. Chem. Int. Ed. 2013, 52, 3746−3749. (4) (a) Mastalerz, M.; Chem. Commun. 2008, 4756−4758. (b) Lydon, D. P.; Campbell, N. L.; Adams, D. J.; Cooper, A. I. Synth. Commun. 2011, 41, 2146−2151. (5) (a) Wang, Q.; Zhang, C.; Noll, B. C.; Long, H.; Jin, Y.; Zhang, W. Angew. Chem. Int. Ed. 2014, 53, 10663−10667. (b) Lee S.; Yang. A.; Moneypenny II, T. P.; Moore, J. S. J. Am. Chem. Soc. 2016, 138, 2182−2185. (6) (a) Takahagi, H.; Fujibe, S.; Iwasawa, N. Chem. Eur. J. 2009, 15, 13327−13330. (b) Zhang, G.; Presly, O.; White, F.; Oppel, I. M.; Mastalerz, M. Angew. Chem. Int. Ed. 2014, 53, 1516−1520. (7) (a) Tozawa, T.; Jones, J. T. A.; Swamy, S. I.; Jiang, S.; Adams, D. J.; Shakespeare, S.; Clowes, R.; Bradshaw, D.; Hasell, T.; Chong, S. Y.; Tang, C.; Thompson, S.; Parker, J.; Trewin, A.; Bacsa, J.; Slawin, A. M. Z.; Steiner, A.; Cooper, A. I. Nat. Mater. 2009, 8, 973−978. (b) Mastalerz, M.; Schneider, M. W.; Oppel, I. M.; Presly, O. Angew. Chem. Int. Ed. 2011, 50, 1046−1051. (8) (a) Liu, X.; Liu, Y.; Li, G.; Warmuth, R. Angew. Chem. Int. Ed. 2006, 45, 901−904. (b) Hong, S.; Rohman, Md. R.; Jia, J.; Kim, Y.; Moon, D.; Kim, Y.; Ko, Y. H.; Lee, E.; Kim, K. Angew. Chem. Int. Ed. 2015, 54, 13241−13244. (9) (a) Shen, Y.; Chen, C.-F. Chem. Rev. 2012, 112, 1463−1535. (b) Gingras, M.; Chem. Soc. Rev. 2013, 42, 968−1006. (10) (a) Phillips, K. E. S.; Katz, T. J.; Jockusch, S.; Lovinger, A. J.; Turro, N. J. J. Am. Chem. Soc. 2001, 123, 11899−11907. (b) Field, J. E.; Muller, G.; Riehl, J. P.; Venkataraman, D. J. Am. Chem. Soc. 2003, 125, 11808−11809. (11) (a) Takenaka, N.; Sarangthem, R. S.; Captain, B. Angew. Chem. Int. Ed. 2008, 47, 9708−9710. (b) Yavari, K.; Aillard, P.; Zhang, Y.; Nuter, F.; Retailleau, P.; Voituriez, A.; Marinetti, A. Angew. Chem. Int. Ed. 2014, 53, 861−865. (c) Sánchez, I. G.; Šámal, M.; Nejedlý, J.; Karras, M.; Klívar, J.; Rybáček, J.; Buděšínský, M.; Bednárová, L.; Seidlerová, B.; Stará, I. G.; Starý, I. Chem. Commun. 2017, 53, 4370−4373. (12) (a) An, Z.; Yamaguchi, M. Chem. Commun. 2012, 48, 7383−7385. (b) Schweinfurth, D.; Zalibera, M.; Kathan, M.; Shen, C.; Mazzolini, M.; Trapp, N.; Crassous, J.; Gescheidt, G.; Diederich, F. J. Am. Chem. Soc. 2014, 136, 13045−13052. (c) Anger, E.; Iida, H.; Yamaguchi, T.; Hayashi, K.; Kumano, D.; Crassous, J.; Vanthuyne, N.; Roussel, C.; Yashima, E. Polym. Chem. 2014, 5, 4909−4914. (13) (a) Shigeno, M.; Kushida, Y.; Yamaguchi, M. J. Am. Chem. Soc. 2014, 136, 7972−7980. (b) Shen, C.; Loas, G.; Srebro-Hooper, M.; Vanthuyne, N.; Toupet, L.; Cador, O.; Paul, F.; Navarrete, J. T. L.; Ramírez, F. J.; Nieto-Ortega, B.; Casado, J.; Autschbach, J.; Vallet, M.; Crassous, J. Angew. Chem. Int. Ed. 2016, 55, 8062−8066. (14) (a) Yang, Y.; Da Costa, R. C.; Fuchter, M. J.; Campbell, A. J. Nat. Photonics 2013, 7, 634−638. (b) Brandt, J. R.; Wang,


Page 5 of 6 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Journal of the American Chemical Society X.; Yang, Y.; Campbell, A. J.; Fuchter, M. J. J. Am. Chem. Soc. 2016, 138, 9743−9746. (15) (a) Fox, J. M.; Lin, D. J. Org. Chem. 1998, 63, 2031−2038. (b) Anger, E.; Srebro, M.; Vanthuyne, N.; Toupet, L.; Rigaut, S.; Roussel, C.; Autschbach, J.; Crassous, J.; Réau, R. J. Am. Chem. Soc. 2012, 134, 15628−15631. (16) Damhus, T.; Schäffer, C. E. Inorg. Chem. 1983, 22, 2406−2412. (17) (a) Newman, M. S.; Darlak, R. S.; Tsai, L. J. Am. Chem. Soc. 1967, 89, 6191−6193. (b) Brickell, W. S.; Brown, A.; Kemp, C. M.; Mason, S. F. J. Chem. Soc. A: Inorg. Phys. Theor. 1971, 756−760. (18) (a) Xuan, W.; Zhang, M.; Liu, Y.; Chen, Z.; Cui, Y. J. Am. Chem. Soc. 2012, 134, 6904−6907. (b) Chen, L; Reiss, P. S.; Chong, S. Y.; Holden, D.; Jelfs, K. E.; Hasell, T.; Little, M. A.; Kewley, A.; Briggs, M. E.; Stephenson, A.; Thomas, K. M.; Armstrong, J. A.; Bell, J.; Busto, J.; Noel, R.; Liu, J.; Strachan, D. M.; Thallapally, P. K.; Cooper, A. I. Nat. Mater. 2014, 13, 954−960. (c) Zhang, J.-H.; Xie, S.-M.; Chen, L.; Wang, B.-J.; He, P.-G.; Yuan, L.-M. Anal. Chem. 2015, 87, 7817−7824. (d) Gropp, C.; Trapp, N.; Diederich, F. Angew. Chem. Int. Ed. 2016, 55, 14444−14449.




Page 6 of 6

Chiral Organic Cages with a Triple-Stranded Helical Structure Derived

Recommend Documents