A Route to Enantiopure (O-Methyl)6-2,6-Helic[6]arenes: Synthesis of

Aug 31, 2018 - J. Org. Chem. , 2018, 83 (19), pp 11532–11540. DOI: 10.1021/acs.joc. ... Journal of the American Chemical Society. Nakatsuka, Yasuda,...
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A Route to Enantiopure (O‑Methyl)6‑2,6-Helic[6]arenes: Synthesis of Hexabromo-Substituted 2,6-Helic[6]arene Derivatives and Their Suzuki−Miyaura Coupling Reactions Jia-Qi Wang,#,†,‡ Jing Li,#,†,‡ Geng-Wu Zhang,† and Chuan-Feng Chen*,†,‡ †

J. Org. Chem. 2018.83:11532-11540. Downloaded from pubs.acs.org by UNIV OF SUNDERLAND on 10/05/18. For personal use only.

Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China ‡ University of Chinese Academy of Sciences, Beijing 100049, China S Supporting Information *

ABSTRACT: A route to enantiopure (O-methyl)6-2,6-helic[6]arenes (+)-P-2 and (−)-M-2 has been provided. By the reaction of enantiopure triptycene precursors (+)-1 and (−)-1 in refluxed o-DCB for 12 h in the presence of catalytic amount of FeCl3, and then followed by treatment of the obtained oligomers under the same conditions, (+)-P-2 and (−)-M-2 could be obtained in 51% and 53% total yield, respectively. It was also found that racemic and enantiopure (O-methyl)6-2,6-helic[6]arenes could be easily brominated by Br2 to give the corresponding hexabromo-substituted helic[6]arene derivatives rac-4, (+)-P-4, and (−)-M-4 in high yields. The crystal structure of (+)-P-4 further confirmed the absolute configuration of the helic[6]arenes and their derivatives. Moreover, a series of hexaaryl-substituted helic[6]arene derivatives 5a−f with deepened cavities could be conveniently synthesized in 55−71% yield by Suzuki−Miyaura coupling reactions of 4 and arylboronic acids. rac-5a could encapsulate chloroform and exhibit self-sorting stacking in solid state. Enantiopure (+)-P-5a−f and (−)-M-5a−f showed mirror images in their CD spectra.

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INTRODUCTION Macrocyclic arenes, including calixarenes,1 resorcinarene,2 cyclotriveratrylene,3 pillararenes,4 biphen[n]arenes,5 and their analogues,6 are one of most important and most studied synthetic macrocyclic hosts during the last decades for their welldefined cavities, facile modifications, and wide applications in host−guest chemistry,7 self-assembly,8 catalysis,9 biomedicine,10 and materials science.11 Chiral macrocyclic arenes12 as one kind of important synthetic macrocyclic host have also attracted much attention for their potential applications in chiral molecular recognition, chiral assemblies, and so on. Generally, chiral macrocyclic arenes could be obtained by introducing a chiral auxiliary into the macrocyclic skeleton,13 building inherent chirality14 and constructing planar chirality based on pillararenes.15 Recently, we16 reported a new kind of chiral macrocyclic arenes named as helicarenes, which were composed of chiral 2,6-dihydroxyltriptycene building blocks bridged by methylene groups. We also found the helicarenes and their derivatives showed wide potential applications in chiral recognition,16 stimuli-responsive host−guest complexations,17 and molecular machines.18 Previously, we synthesized the racemic (O-methyl)6-2, 6-helic[6]arene in 15% isolated yield by treatment of the racemic 2,6-dimethoxyl-3-hydroxymethyltriptycene with a catalytic amount of p-toluenesulfonic acid.16 The enantiopure 2, 6-helic[6]arenes could be then obtained by introducing chiral auxiliaries, separation with conventional column chromatography, © 2018 American Chemical Society

and removing the chiral auxiliaries. Obviously, the low yield of the racemic macrocycle and the tedious resolution process will limit the development of helicarene chemistry to some extent. Herein, we report a route to the direct synthesis of P- and M-(O-methyl)6-2,6-helic[6]arenes by the treatment of enantiopure 2,6-dimethoxyl-3-hydroxymethyltriptycene precursorsin refluxed o-dichlorobenzene (o-DCB) in the presence of catalytic amount of ferric trichloride (FeCl3). We also found that the racemic and enantiopure (O-methyl)6-2,6-helic[6]arenes could be easily brominated by Br2 to give the corresponding hexabromo-substituted 2,6-helic[6]arenes derivatives in high yields, which further provided a series of hexaarylsubstituted derivatives with deepened cavities in good yields by Suzuki−Miyaura coupling reactions. Moreover, it was also found the racemic hexaphenyl-substituted helic[6]arene could encapsulate chloroform and exhibit self-sorting stacking in solid state, and the enantiomeric hexaaryl-substituted derivatives showed mirror images in their CD spectra.

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RESULTS AND DISCUSSION A Route to Enantiopure (O-Methyl)6-2,6-helic[6]arenes. Inspired by the synthesis of racemic (O-methyl)6-2,6-helic[6]arene rac-2 reported previously,16 it is envisaged that if the enantiopure 2,6-dimethoxyl-3-hydroxymethyltriptycene derivatives Received: June 7, 2018 Published: August 31, 2018 11532

DOI: 10.1021/acs.joc.8b01437 J. Org. Chem. 2018, 83, 11532−11540

Article

The Journal of Organic Chemistry Scheme 1. Synthetic Route to Enantiopure (+)-P-2 and (−)-M-2

were used as the precursors, the enantiopure (O-methyl)6-2, 6-helic[6]arenes could be efficiently and directly obtained in one step. Moreover, the diastereomeric byproducts generated during the cyclization could also be diminished, while the yields of the target (O-methyl)6-2,6-helic[6]arenes could be efficiently improved. As shown in Scheme 1, the convenient resolution of racemic 2,6-dimethoxyl-3-hydroxymethyltriptycene rac-116 with HPLC on a chiral column (Figure S1) gave enantiopure (+)-1 and (−)-1. After the cyclization condition was optimized, it was found that o-DCB with high boiling point used as the solvent and easily available FeCl3 used as the catalyst could be beneficial for the cyclization reactions. Size-exclusion chromatography (SEC)19 was further used to determine the optimal reaction time. As shown in Figure S4, by comparison with the retention time of (−)-M-2 at 27.23 min, it was found that after (−)-1 was treated for even 3 min in refluxed o-DCB in the presence of a catalytic amount of FeCl3, the target cyclization product was produced; meanwhile, alot of oligomeric byproducts with a retention time at 20−27 min were formed. As time went on, the amount of oligomers gradually decreased, while (−)-M-2 obviously increased. After the reaction was carried out for 12 h, the peak of the cyclization product reached a maximum, and then no obvious changes of the SEC traces were observed. Therefore, under the optimal reactions, treatment of (−)-1 with a catalytic amount of FeCl3 in refluxed o-DCB for 12 h gave cyclic trimer (−)-M-2 in 43% isolated yield (Scheme 1), while (+)-oligomer-I generated during the cyclization was also obtained. It was interesting that (+)-oligomer-I could also be transformed into (−)-M-2 in 10% yield under the same reaction conditions, which might process a dynamic covalent reaction.20 Similarly, by treatment of (+)-1 with a catalytic amount of FeCl3 in refluxed o-DCB for 12 h, and then followed by treatment of (−)-oligomer-I under the same conditions, (+)-P-2 could be obtained in 51% total yield. The CD spectra of (+)-P-2 and (−)-M-2 in CH2Cl2 displayed perfect mirror images (Figure 1).

Figure 1. CD Spectra of (+)-P-2 (red line) and (−)-M-2 (black line) (CH2Cl2, c = 2 × 10−5 M, T = 298 K).

Synthesis of Hexabromo-Substituted 2,6-Helic[6]arene Derivatives. Aryl bromides were very useful precursors for organic synthesis, and they could be easily obtained by bromination of aromatic compound. Hence, we first tested the bromination of racemic (O-methyl)6-2,6-helic[6]arene with bromine in CH2Cl2 at room temperature. Because methoxy groups are strong electron-donating groups, it was found that the bromination reaction only occurred at ortho-position of the methoxyl groups following the orientation effect to produce the hexabromo-substituted (O-methyl)6-2,6-helic[6]arene rac-3 in 88% yield, which was demethylated by BBr3 in dichloromethane to give rac-4 in 95% yield (Scheme 2). The single crystal of rac-3 was obtained by slow evaporation of rac-3 in a mixed solvent of chloroform and acetonitrile, and the crystal structure (Figure 2) showed that the six bromine atoms were all positioned at the ortho-position of the methoxyl groups, in which three bromine atoms were at one side and the other three bromine atoms at another side of the macrocycle. Following the same synthetic method, we also conveniently synthesized enantiopure hexabromo-substituted 2,6-helic[6]arenes (+)-P-4 and (−)-M-4 starting from enantiopure (O-methyl)6-2, 11533

DOI: 10.1021/acs.joc.8b01437 J. Org. Chem. 2018, 83, 11532−11540

Article

The Journal of Organic Chemistry Scheme 2. Synthesis of Racemic Hexabromo-Substituted 2,6-Helic[6]arene

rac-3, enantiopure (+)-P-3 or (−)-M-3 showed better solubility in common organic solvent including chloroform, dichloromethane, acetone, and so on. Treatment of (+)-P-3 or (−)-M-3 with BBr3 in dichloromethane gave (+)-P-4 or (−)-M-4, respectively, in high yield. Moreover, we also obtained a single crystal of (+)-P-4 by slow evaporation of (+)-P-4 in a mixed solvent of dichloromethane and n-hexane, and the crystal structure showed P configuration of the macrocycle, which further verified absolute configuration of the 2,6-helic[6]arenes and their derivatives. Suzuki−Miyaura Coupling Reactions of HexabromoSubstituted 2,6-Helic[6]arene Derivatives. Hexabromosubstituted 2,6-helic[6]arene derivatives can be utilized as useful precursors for constructing various functional helicarene derivatives. Consequently, a series of hexaaryl-substituted 2, 6-helic[6]arene derivatives with deepened cavities for further applications in molecular recognition and assemblies could be conveniently synthesized by Suzuki−Miyaura coupling reactions. As shown in Scheme 4, rac-5a was synthesized in 60% yield by the treatment of the hexabromo-substituted 2,6-helic[6]arene rac-4 withan excess amount of phenylboronic acid in a mixed solution of toluene, ethanol, and water in the presence of Cs2CO3 and Pd(PPh3)4. Under the same reaction conditions,

Figure 2. Crystal structures of (a) top view and (b) side view of rac-3, and (c) top view and (d) side view of (+)-P-4. Hydrogen atoms were omitted for clarity.

6-helic[6]arenes. As shown in Scheme 3, when (+)-P-2 or (−)-M-2 was treated with bromine in CH2Cl2, enantiopure (+)-P-3 or (−)-M-3 was obtained in high yield. Compared with

Scheme 3. Synthesis of Enantiopure Hexabromo-Substituted 2,6-Helic[6]arenes

11534

DOI: 10.1021/acs.joc.8b01437 J. Org. Chem. 2018, 83, 11532−11540

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The Journal of Organic Chemistry Scheme 4. Suzuki−Miyaura Coupling Reactions of rac-4

a series of racemic hexaaryl-substituted 2,6-helic[6]arene derivatives (rac-5b−f) were obtained in 55−70% yields by the reaction of rac-4 with the corresponding arylboronic acids (Table 1). It was found the arylboronic acids with electron-donating groups Table 1. Synthesis of rac-5 entry

product

Ar

yield (%)

1 2 3 4 5 6

rac-5a rac-5b rac-5c rac-5d rac-5e rac-5f

C6H5 4-MeOC6H4 4-MeC6H4 4-EtC6H4 4-FC6H4 4-ClC6H4

60 68 64 70 55 58

gave higher yields, while yields of the products were lower for the arylboronic acids with electron-withdrawing groups. The hexaaryl-substituted 2,6-helic[6]arene derivatives rac-5a−f also showed good solubility in polar solvents including acetone, methanol, acetonitrile, and so on. Moreover, the helic[6]arene derivatives rac-5a−f showed simple 1H NMR and 13C NMR spectra (Figures S32−S43), which were consistent with their high symmetry. The UV−vis and fluorescence spectra of rac-5a were further measured in CH2Cl2, and the maximum absorption at 299 nm and maximum emission at 364 nm were observed (Figure 3). For other helicarene derivatives rac-5b−f, similar spectral properties were also shown (Figures S5 and S6). A single crystal of rac-5a was obtained by slow evaporation of rac-5a in chloroform solution. As shown in Figure 4, the crystal structure showed that rac-5a possessed C3 symmetry and a deepened cavity. Three phenyl groups were positioned at one side of the macrocycle, and the other three phenyl groups were at another side. The total depth of rac-5a was 13.72 Å, which was significantly larger than those of rac-2,6-helic[6]arene (5.28 Å)16 and rac-2 (8.83 Å, Figure S7). It was also found that one benzene ring of triptycene on one macrocycle was positioned into the cavity of another macrocyclic molecule, which resulted in a zigzag structure viewed along b axle (Figure 4c). Moreover, macrocycle rac-5a showed self-sorting property in solid state, in which the molecules with P configurations only formed zigzag stacking with P configurations, and vice versa (Figure 4d). Furthermore, we found that the chloroform molecule was encapsulated in the cavity of the macrocycle in solid state. According to the same synthetic method, the enantiopure hexaaryl-substituted 2,6-helic[6]arene derivatives (+)-P-5a−f and (−)-M-5a−f were also synthesized in medium to high yields by Suzuki−Miyaura coupling reactions of (+)-P-4 or (−)-M-4 with the arylboronic acids (Scheme 5), and the results are summarized in Table 2. The CD spectra of enantiopure (+)-P-5a/(−)-M-5a were determined in CH2Cl2, and they

Figure 3. (a) UV−vis and (b) fluorescence spectra of rac-5a (CH2Cl2, c = 2 × 10−5 M).

Figure 4. X-ray single crystal structure of rac-5a@CHCl3: (a) top view and (b) side view. (c) Zigzag stacking along b axle. (d) Selfsorting stacking between P configurations (blue color) and M configurations (red color). Hydrogen atoms were omitted for clarity.

showed good mirror images (Figure 5). Similarly, the CD spectra of enantiopure (+)-P-5b−f/(−)-M-5b−f also exhibited good mirror images, respectively (Figure S11). 11535

DOI: 10.1021/acs.joc.8b01437 J. Org. Chem. 2018, 83, 11532−11540

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The Journal of Organic Chemistry Scheme 5. Suzuki−Miyaura Coupling Reactions of (+)-P-4 and (−)-M-4

Table 2. Synthesis of (+)-P-5a−f and (−)-M-5a−f entry

Ar

product

yield (%)

entry

Ar

product

yield (%)

1 2 3 4 5 6

C6H5 4-MeOC6H4 4-MeC6H4 4-EtC6H4 4-FC6H4 4-ClC6H4

(+)-P-5a (+)-P-5b (+)-P-5c (+)-P-5d (+)-P-5e (+)-P-5f

63 69 67 71 58 59

7 8 9 10 11 12

C6H5 4-MeOC6H4 4-MeC6H4 4-EtC6H4 4-FC6H4 4-ClC6H4

(−)-M-5a (−)-M-5b (−)-M-5c (−)-M-5d (−)-M-5e (−)-M-5f

62 70 65 70 56 58

(−)-M-4 in high yields. The crystal structure of (+)-P-4 further confirmed the absolute configuration of the helic[6]arenes and their derivatives. Moreover, a series of hexaaryl-substituted helic[6]arene derivatives 5a−f with deepened cavities could be conveniently synthesized in 55−71% yield by Suzuki−Miyaura coupling reactions of 4 and arylboronic acids. rac-5a could encapsulate chloroform and exhibit self-sorting stacking in solid state. Enantiopure (+)-P-5a−f and (−)-M-5a−f all showed mirror images in their CD spectra. Undoubtedly, the easily available enantiopure 2,6-helic[6]arenes and their derivatives will be very important and meaningful for the development of helicarene chemistry. Our further studies will focus on functionalization of the helic[6]arenes and their applications in supramolecular chemistry.

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Figure 5. CD spectra of (+)-P-5a and (−)-M-5a (CH2Cl2, c = 2 × 10−5 M, T = 298 K).

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EXPERIMENTAL SECTION

General Information. All the reagents were commercially available and used without further purification. Reactions were carried out under inert and anhydrous conditions unless otherwise noted. Flash column chromatography was performed on 200−300 mesh silica gel. 1H and 13C NMR spectra were measured at 298 K. The ionization methods used in mass spectrometry were atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI). Specific rotation, UV−vis, fluorescence, and CD spectra were measured at 298 K in CH2Cl2. Melting points, taken on an electrothermal melting point apparatus, were uncorrected. SEC in THF was performed using four Waters columns (HR2, HR1, HR0.5, HR0.5), a Waters HPLC 1515 pump, and a Waters 2489 detector. THF was used as the eluent at a flow rate of 1 mL min−1. Polystyrene standards

CONCLUSIONS (O-Methyl)6-2,6-helic[6]arenes (+)-P-2 and (−)-M-2 could be directly prepared in 51% and 53% total yield, respectively, by treatment of enantiopure triptycene precursors (+)-1 and (−)-1 with a catalytic amount of FeCl3 in refluxed o-DCB for 12 h and then followed by treatment of the obtained oligomers under the same conditions. We also found that the racemic and enantiopure (O-methyl)6-2,6-helic[6]arenes could be easily brominated by Br2 to give the corresponding hexabromosubstituted 2,6-helic[6]arene derivatives rac-4, (+)-P-4, and 11536

DOI: 10.1021/acs.joc.8b01437 J. Org. Chem. 2018, 83, 11532−11540

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The Journal of Organic Chemistry

acetone-d6) δ 7.46 (s, 6H), 7.44−7.38 (m, 12H), 6.98−6.97 (m, 6H), 5.63 (s, 6H), 3.82 (s, 6H); 13C NMR (125 MHz, acetone-d6) δ 148.8, 146.2, 144.7, 138.8, 126.9, 126.1, 126.0, 124.4, 109.4, 54.0; HRMS (APCI) m/z: [M + H]+ calcd for C63H37Br6O6 1368.7629; found 1368.7658. (+)-P-Hexabromo-(O-methyl)6-2,6-helic[6]arene (+)-P-3. To the solution of (+)-P-2 (100 mg, 0.1 mmol) in CH2Cl2 (20 mL) was added a solution of bromine (0.5 mL) in CH2Cl2 (5 mL). The mixture was stirred at ambient temperature for 1 h and then quenched with saturated NaHSO3 aqueous solution. The organic layer was separated, washed with brine three times, and dried with anhydrous MgSO4. The organic layer was evaporated and then purified by column chromatography on silica gel (petroleum ether/dichloromethane, 1:3, v/v) to afford (+)-P-3 (136 mg, 91% yield) as a white solid. Mp > 300 °C; [α]D25 = +206° (c = 0.5, CH2Cl2); 1H NMR (400 MHz; acetone-d6) δ 7.53−7.46 (m, 12H), 7.04−7.03 (m, 6H), 5.84 (s, 6H), 3.80 (s, 18H), 3.77 (s, 6H); 13C NMR (125 MHz, acetone-d6) δ 152.3, 144.7, 144.7, 141.6, 132.3, 125.9, 125.5, 123.9, 113.8, 60.4, 52.9; HRMS (APCI) m/z: [M + H] + calcd for C69H49Br6O6 1452.8568; found 1452.8562. (+)-P-Hexabromo-2,6-helic[6]arene (+)-P-4. To the solution of (+)-P-3 (145 mg, 0.1 mmol) in anhydrous CH2Cl2 (10 mL) under N2 atmosphere was added a solution of BBr3 (0.5 mL) in CH2Cl2 (5 mL). The mixture was stirred at 0 °C for 4 h and then quenched with water. The organic layer was separated, washed with brine three times, and dried with anhydrous MgSO4. The organic layer was evaporated and then purified by column chromatography on silica gel (petroleum ether/dichloromethane, 1:5, v/v) to afford (+)-P-4 (137 mg, 95% yield) as a white solid. Mp > 300 °C; [α]D25 = 146° (c = 0.5, CH2Cl2); 1H NMR (500 MHz; acetone-d6) δ 7.46 (s, 6H), 7.44−7.38 (m, 12H), 6.98−6.97 (m, 6H), 5.63 (s, 6H), 3.82 (s, 6H); 13C NMR (125 MHz, acetone-d6) δ 148.8, 146.2, 144.7, 138.8, 126.9, 126.1, 126.0, 124.4, 109.4, 54.0; HRMS (APCI) m/z: [M + H]+ calcd for C63H37Br6O6 1368.7629; found 1368.7628. (−)-M-Hexabromo-(O-methyl)6-2,6-helic[6]arene (−)-M-3. Following the same synthetic method of (+)-P-3, (−)-M-3 as a white solid was obtained (134 mg, 90% yield). Mp > 300 °C; [α]D25 = −204° (c = 0.5, CH2Cl2); 1H NMR (400 MHz; acetone-d6) δ 7.53− 7.46 (m, 12H), 7.04−7.03 (m, 6H), 5.84 (s, 6H), 3.80 (s, 18H), 3.77 (s, 6H); 13C NMR (125 MHz, acetone-d6) δ 152.3, 144.7, 144.7, 141.6, 132.3, 125.9, 125.5, 123.9, 113.8, 60.4, 52.9; HRMS (APCI) m/z: [M + H] + calcd for C69H49Br6O6 1452.8568; found 1452.8570. (−)-M-Hexabromo-2,6-helic[6]arene (−)-M-4. Following the synthetic method of (+)-P-4, (−)-M-4 as a white solid was obtained (137 mg, 96% yield). Mp > 300 °C; [α]D25 = −144° (c = 0.5, CH2Cl2); 1H NMR (500 MHz; acetone-d6) δ 7.46 (s, 6H), 7.44−7.38 (m, 12H), 6.98−6.97 (m, 6H), 5.63 (s, 6H), 3.82 (s, 6H); 13C NMR (125 MHz, d6- acetone) δ 148.8, 146.2, 144.7, 138.8, 126.9, 126.1, 126.0, 124.4, 109.4, 54.0; HRMS (APCI) m/z: [M + H]+ calcd for C63H37Br6O6 1368.7629; found 1368.7663. Racemic Hexaphenyl-2,6-helic[6]arene rac-5a. A mixture of rac-4 (50 mg, 0.037 mmol), K2CO3 (100 mg, 0.73 mmol), phenylboronic acid (45 mg, 0.37 mmol), and Pd(PPh3)4 (4 mg, 0.0037 mmol) was dissolved in toluene/ethanol/water (4.5 mL, 4:4:1, v/v/v) in a Schlenk tube. The mixture was stirred at 80 °C in oil bath for 12 h under N2 atmosphere and then quenched with water. The reaction mixture was extracted by ethyl acetate. The organic layer was separated, washed with brine for three times, and then dried over anhydrous MgSO4. The organic layer was evaporated and purified by column chromatography on silica gel (petroleum ether/dichloromethane, 1:3, v/v) to afford rac-5a (30.0 mg, 60% yield) as a white solid. Mp > 300 °C; 1H NMR (500 MHz, acetone-d6) δ 7.62 (t, J = 6.9 Hz, 6H), 7.59−7.49 (m, 12H), 7.44 (d, J = 6.9 Hz, 6H), 7.30 (d, J = 7.4 Hz, 6H), 7.26 (s, 6H), 7.14−7.13 (m, 6H), 6.89−6.88 (m, 6H), 6.22 (s, 6H), 4.95 (s, 6H), 3.68 (s, 6H); 13C NMR (125 MHz, acetone-d6) δ 148.7, 147.7, 143.5, 137.2, 136.7, 132.1, 131.3, 130.0, 129.7, 128.6, 126.1, 125.9, 125.4, 124.9, 123.7 51.7; HRMS (APCI) m/z: [M + H]+ calcd for C99H67O6 1352.4971; found 1352.4962. Racemic Hexa(4-methoxylphenyl)-2,6-helic[6]arene rac-5b. Following the same synthetic method of rac-5a, rac-5b as a white solid

were used for the calibration. Optical resolutions were carried out by HPLC using the column (Chiralpak IG, 50 mm × 250 mm). Racemic 2,6-dimethoxyl-3-hydroxymethyltriptycene (rac-1) was prepared according to the reported method.16 Enantiopure 2,6-Dimethoxy-3-hydroxymethyltriptycenes (+)-1 and (−)-1. (+)-1 and (−)-1 were easily obtained by HPLC resolution of rac-1 with methanol as eluent. For (+)-1: mp 108−110 °C; [α]D25 = +21° (c = 1.0, CH2Cl2); 1H NMR (300 MHz, CDCl3) δ 7.37−7.34 (m, 2H), 7.30 (s, 1H), 7.25 (s, 1H), 7.06−6.90 (m, 4H), 6.48 (dd, J = 8.0, 2.4 Hz, 1H), 5.32 (d, J = 4.2 Hz, 2H), 4.57 (s, 2H), 3.83 (s, 3H), 3.73 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 157.4, 155.1, 147.3, 147.1, 145.6, 145.5, 137.6, 137.5, 125.3, 125.2, 125.0, 124.4, 124.1, 123.5, 123.4, 110.8, 109.3, 107.2, 62.0, 55.7, 55.6, 53.7, 53.6; HRMS (APCI) m/z: [M + H]+ calcd for C23H21O3 345.1485; found 345.1476. For (−)-1: mp 106−108 °C; [α]D25 = −19° (c = 1.0, CH2Cl2); 1H NMR (300 MHz, CDCl3) δ 7.37−7.34 (m, 2H), 7.30 (s, 1H), 7.25 (s, 1H), 7.06−6.90 (m, 4H), 6.48 (dd, J = 8.0, 2.4 Hz, 1H), 5.32 (d, J = 4.2 Hz, 2H), 4.57 (s, 2H), 3.83 (s, 3H), 3.73 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 157.4, 155.1, 147.3, 147.1, 145.6, 145.5, 137.6, 137.5, 125.3, 125.2, 125.0, 124.4, 124.1, 123.5, 123.4, 110.8, 109.3, 107.2, 62.0, 55.7, 55.6, 53.7, 53.6; HRMS (APCI) m/z: [M + H]+ calcd for C23H21O3 345.1485; found 345.1479. (+)-P-(O-Methyl)6-2,6-helic[6]arene (+)-P-2. A mixture of (+)-1 (2.0 g, 5.84 mmol) and catalytic amount of ferric trichloride (96 mg, 0.6 mmol) in o-DCB (800 mL) was heated at 100 °C in oil bath for 12 h. After cooling to room temperature, the solvent was removed in vacuo. The residue was separated by flash column chromatography on silica gel (petroleum ether/dichloromethane, 1:1 v/v) to give compound (+)-P-2 (780 mg, 41% yield) as a white yellow solid, and (+)-oligomer-I. (+)-Oligomer-I separated by flash column chromatography was treated with the same reaction conditions as described above to afford another (+)-P-2 (192 mg) in 10% yield. Mp > 300 °C; [α]D25 = +330° (c = 1.0, CH2Cl2); 1H NMR (300 MHz, CD2Cl2) δ 7.34 (s, 6H), 7.28−7.25 (m, 6H), 6.93−6.90 (m, 6H), 6.85 (s, 6H), 5.11 (s, 6H), 3.85 (s, 18H), 3.65 (s, 6H); 13 C NMR (125 MHz, CD2Cl2) δ 154.6, 147.0, 145.0, 137.6, 127.0, 125.9, 125.2, 123.4, 107.7, 56.3, 28.8; HRMS (ESI) m/z: [M]+ calcd for C69H54O6 978.3920; found 978.3942. (−)-M-(O-Methyl)6-2,6-helic[6]arene (−)-M-2. Following the same synthetic method of (+)-P-2, (−)-M-2 as a white yellow solid was obtained (1.01 g, 53% total yield). Mp > 300 °C; [α]D25 = −324° (c = 1.0, CH2Cl2); 1H NMR (300 MHz, CD2Cl2) δ 7.34 (s, 6H), 7.28−7.25 (m, 6H), 6.93−6.90 (m, 6H), 6.85 (s, 6H), 5.11 (s, 6H), 3.85 (s, 18H), 3.65 (s, 6H); 13C NMR (125 MHz, CD2Cl2) δ 154.6, 147.0, 145.0, 137.6, 127.0, 125.9, 125.2, 123.4, 107.7, 56.3, 28.8; HRMS (ESI) m/z: [M]+ calcd for C69H54O6 978.3920; found: 978.3928. Racemic Hexabromo-(O-methyl)6-2,6-helic[6]arene (rac-3). Rac-2 (100 mg, 0.1 mmol) was dissolved in CH2Cl2 (20 mL), and a solution of bromine (0.5 mL) in CH2Cl2 (5 mL) was added. The mixture was stirred at ambient temperature for 1 h and then quenched with saturated NaHSO3 aqueous solution. The organic layer was separated, washed with brine three times, and dried with anhydrous MgSO4. The organic layer was evaporated and then recrystallized by petroleum ether/dichloromethane (1:1, v/v) to afford rac-3 (130 mg, 88% yield) as a white solid. Mp > 300 °C; 1H NMR (400 MHz; acetone-d6) δ 7.53−7.46 (m, 12H), 7.04−7.03 (m, 6H), 5.84 (s, 6H), 3.80 (s, 18H), 3.77 (s, 6H); 13C NMR (125 MHz, acetone-d6) δ 152.3, 144.7, 144.7, 141.6, 132.3, 125.9, 125.5, 123.9, 113.8, 60.4, 52.9; HRMS (APCI) m/z: [M + H] + calcd for C69H49Br6O6 1452.8568; found 1452.8587. Racemic Hexabromo-Substituted 2,6-Helic[6]arene (rac-4). To the solution of rac-3 (145 mg, 0.1 mmol) in anhydrous CH2Cl2 (10 mL) under N2 atmosphere was added a solution of BBr3 (0.5 mL) in CH2Cl2 (5 mL). The mixture was stirred at 0 °C for 4 h and then quenched with water. The organic layer was separated, washed with brine three times, and dried with anhydrous MgSO4. The organic layer was evaporated and then purified by column chromatography on silica gel (petroleum ether/dichloromethane, 1:5, v/v) to afford rac-4 (137 mg, 95% yield) as a white solid. Mp > 300 °C; 1H NMR (500 MHz; 11537

DOI: 10.1021/acs.joc.8b01437 J. Org. Chem. 2018, 83, 11532−11540

Article

The Journal of Organic Chemistry

δ 7.32−7.21 (m, 18H), 7.17 (d, J = 8.3 Hz, 6H), 7.12−7.11 (m, 6H), 7.04 (d, J = 6.8 Hz, 6H), 6.88−6.85 (m, 6H), 6.16 (s, 6H), 4.95 (s, 6H), 3.93 (s, 18H), 3.66 (s, 6H); 13C NMR (100 MHz, acetone-d6) δ 160.3, 148.9, 147.7, 143.8, 137.2, 133.5, 132.3, 128.5, 126.0, 125.4, 124.6, 123.7, 115.5, 115.1, 55.7, 51.8; HRMS (APCI) m/z: [M + H] + calcd for C105H79O12 1532.5605; found 1532.5597. (+)-P-Hexa(4-methylphenyl)-2,6-helic[6]arene (+)-P-5c. Following the same synthetic method of (+)-P-5a, (+)-P-5c as a white solid was obtained (35.2 mg, 67% yield). Mp > 300 °C; [α]D25 = +244° (c = 0.5, CH2Cl2); Mp > 300 °C; 1H NMR (500 MHz; acetone-d6) δ 7.45 (d, J = 7.4 Hz, 6H), 7.27 (s, 6H), 7.26−7.19 (m, 18H), 7.12−7.11 (m, 6H), 6.87−6.86 (m, 6H), 6.11 (s, 5H), 4.98 (s, 6H), 3.68 (s, 6H), 2.52 (s, 18H); 13C NMR (125 MHz, acetone-d6) δ 148.7, 147.6, 143.6, 137.9, 137.2, 133.5, 132.2, 130.8, 130.3, 126.1, 126.7, 125.4, 124.6, 123.7, 51.7, 21.5; HRMS (APCI) m/z: [M + H]+ calcd for C105H79O6 1436.5910; found 1436.5913. (+)-P-Hexa(4-ethylphenyl)-2,6-helic[6]arene (+)-P-5d. Following the same synthetic method of (+)-P-5a, (+)-P-5d as a white solid was obtained (39.4 mg, 71% yield). Mp > 300 °C; [α]D25 = +155° (c = 0.5, CH2Cl2); 1H NMR (500 MHz; acetone-d6): δ 7.48 (d, J = 7.6 Hz, 6H), 7.35 (d, J = 7.7 Hz, 6H), 7.31 (d, J = 7.7 Hz, 6H), 7.29−7.23 (m, 12H), 7.13−7.11 (m, 6H), 6.88−6.86 (m, 6H), 6.09 (s, 6H), 4.98 (s, 6H), 3.67 (s, 6H), 2.83 (q, J = 7.7 Hz, 12H), 1.41 (t, J = 7.6 Hz, 18H); 13C NMR (125 MHz, acetone-d6) δ 147.8, 146.7, 143.4, 142.7, 136.4, 132.9, 131.4, 130.2, 128.6, 128.2, 125.2, 124.9, 124.5, 123.8, 122.8, 50.8, 15.2; HRMS (APCI) m/z: [M + H]+ calcd for C111H91O6 1520.6849; found 1520.6844. (+)-P-Hexa(4-fluorophenyl)-2,6-helic[6]arene (+)-P-5e. Following the same synthetic method of (+)-P-5a, (+)-P-5e as a white solid was obtained (31.0 mg, 58% yield). Mp > 300 °C; [α]D25 = +162° (c = 0.5, CH2Cl2); 1H NMR (500 MHz; acetone-d6) δ 7.44− 7.24 (m, 30H), 7.16−7.14 (m, 6H), 6.89−6.87 (m, 6H), 6.64 (s, 6H), 4.90 (s, 6H), 3.68 (s, 6H); 13C NMR (125 MHz, acetone-d6) δ 164.4, 162.4, 149.0, 147.4, 143.8, 137.1, 134.1, 133.4, 133.1, 126.3, 125.5, 125.1, 123.8, 116.5, 51.6; HRMS (APCI) m/z: [M + H] + calcd for C99H61F6O6 1460.4406; found 1460.4373. (+)-P-Hexa(4-chlorophenyl)-2,6-helic[6]arene (+)-P-5f. Following the same synthetic method of (+)-P-5a, (+)-P-5f as a white solid was obtained (33.6 mg, 59% yield). Mp > 300 °C; [α]D25 = +253° (c = 0.5, CH2Cl2); 1H NMR (500 MHz; acetone-d6) δ 7.65 (d, J = 7.0 Hz 6H), 7.52 (d, J = 7.0 Hz 6H), 7.40−7.26 (m, 18H), 7.19−7.16 (m, 6H), 6.90−6.87 (m, 6H), 6.78 (s, 6H), 4.96 (s, 6H), 3.71 (s, 6H); 13C NMR (125 MHz, acetone-d6) δ 148.0, 146.4, 142.7, 136.3, 134.9, 133.1, 132.9, 132.3, 128.9, 128.8, 125.5, 124.6, 124.1, 122.9, 50.7; HRMS (APCI) m/z: [M + H]+ calcd for C99H61Cl6O6 1558.2603; found 1558.2595. (−)-M-Hexaphenyl-2,6-helic[6]arene (−)-M-5a. A mixture of rac-4 (50 mg, 0.037 mmol), K2CO3 (100 mg, 0.73 mmol), phenylboronic acid (45 mg, 0.37 mmol), and Pd(PPh3)4 (4 mg, 0.0037 mmol) was dissolved in toluene/ethanol/water (4.5 mL, 4:4:1, v/v/v) in a Schlenk tube. The mixture was stirred at 80 °C in oil bath for 12 h under N2 atmosphere and then quenched with water. The reaction mixture was extracted by ethyl acetate. The organic layer was separated, washed with brine for three times, and then dried over anhydrous MgSO4. The organic layer was evaporated and purified by column chromatography on silica gel (petroleum ether/dichloromethane, 1:3, v/v) to afford rac-5a (30.6 mg, 62% yield) as a white solid. Mp > 300 °C; [α]D25 = −184° (c = 0.5, CH2Cl2); 1H NMR (500 MHz, acetone-d6) δ 7.62 (t, J = 6.9 Hz, 6H), 7.59−7.49 (m, 12H), 7.44 (d, J = 6.9 Hz, 6H), 7.30 (d, J = 7.4 Hz, 6H), 7.26 (s, 6H), 7.14−7.13 (m, 6H), 6.99−6.88 (m, 6H), 6.22 (s, 6H), 4.95 (s, 6H), 3.68 (s, 6H); 13 C NMR (125 MHz, acetone-d6) δ 148.7, 147.7, 143.5, 137.2, 136.7, 132.1, 131.3, 130.0, 129.7, 128.6, 126.1, 125.9, 125.4, 124.9, 123.7 51.7; HRMS (APCI) m/z: [M + H]+ calcd for C99H67O6 1352.4971; found 1352.4980. (−)-M-Hexa(4-methoxylphenyl)-2,6-helic[6]arene (−)-M-5b. Following the same synthetic method of (−)-M-5a, (−)-M-5b as a white solid was obtained (30.2 mg, 70% yield). Mp > 300 °C; [α]D25 = −243° (c = 0.5, CH2Cl2); 1H NMR (400 MHz; acetone-d6) δ 7.32− 7.21 (m, 18H), 7.17 (d, J = 8.3 Hz, 6H), 7.12−7.11 (m, 6H), 7.04

was obtained (38.1 mg, 68% yield). Mp > 300 °C; 1H NMR (400 MHz; acetone-d6) δ 7.32−7.21 (m, 18H), 7.17 (d, J = 8.3 Hz, 6H), 7.12−7.11 (m, 6H), 7.04 (d, J = 6.8 Hz, 6H), 6.88−6.85 (m, 6H), 6.16 (s, 6H), 4.95 (s, 6H), 3.93 (s, 18H), 3.66 (s, 6H); 13 C NMR (100 MHz, acetone-d6) δ 160.3, 148.9, 147.7, 143.8, 137.2, 133.5, 132.3, 128.5, 126.0, 125.4, 124.6, 123.7, 115.5, 115.1, 55.7, 51.8; HRMS (APCI) m/z: [M + H] + calcd for C105H79O12 1532.5605; found 1532.5597. Racemic Hexa(4-methylphenyl)-2,6-helic[6]arene rac-5c. Following the same synthetic method of rac-5a, rac-5c as a white solid was obtained (33.6 mg, 64% yield). Mp > 300 °C; 1H NMR (500 MHz; acetone-d6) δ 7.45 (d, J = 7.4 Hz, 6H), 7.27 (s, 6H), 7.26−7.19 (m, 18H), 7.12−7.11 (m, 6H), 6.87−6.86 (m, 6H), 6.11 (s, 5H), 4.98 (s, 6H), 3.68 (s, 6H), 2.52 (s, 18H); 13C NMR (125 MHz, acetone-d6) δ 148.7, 147.6, 143.6, 137.9, 137.2, 133.5, 132.2, 130.8, 130.3, 126.1, 126.7, 125.4, 124.6, 123.7, 51.7, 21.5; HRMS (APCI) m/z: [M + H]+ calcd for C105H79O6 1436.5910; found 1436.5913. Racemic Hexa(4-ethylphenyl)-2,6-helic[6]arene rac-5d. Following the same synthetic method of rac-5a, rac-5d as a white solid was obtained (38.9 mg, 70% yield). Mp > 300 °C; 1H NMR (500 MHz; acetone-d6): δ 7.48 (d, J = 7.6 Hz, 6H), 7.35 (d, J = 7.7 Hz, 6H), 7.31 (d, J = 7.7 Hz, 6H), 7.29−7.23 (m, 12H), 7.13−7.11 (m, 6H), 6.88− 6.86 (m, 6H), 6.09 (s, 6H), 4.98 (s, 6H), 3.67 (s, 6H), 2.83 (q, J = 7.7 Hz, 12H), 1.41 (t, J = 7.6 Hz, 18H); 13C NMR (125 MHz, acetone-d6) δ 147.8, 146.7, 143.4, 142.7, 136.4, 132.9, 131.4, 130.2, 128.6, 128.2, 125.2, 124.9, 124.5, 123.8, 122.8, 50.8, 15.2; HRMS (APCI) m/z: [M + H]+ calcd for C111H91O6 1520.6849; found 1520.6844. Racemic Hexa(4-fluorophenyl)-2,6-helic[6]arene rac-5e. Following the same synthetic method of rac-5a, rac-5e as a white solid was obtained (29.3 mg, 55% yield). Mp > 300 °C; 1H NMR (500 MHz; acetone-d6) δ 7.44−7.24 (m, 30H), 7.16−7.14 (m, 6H), 6.89−6.87 (m, 6H), 6.64 (s, 6H), 4.90 (s, 6H), 3.68 (s, 6H); 13C NMR (125 MHz, acetone-d6) δ 164.4, 162.4, 149.0, 147.4, 143.8, 137.1, 134.1, 133.4, 133.1, 126.3, 125.5, 125.1, 123.8, 116.5, 51.6; HRMS (APCI) m/z: [M + H] + calcd for C99H61F6O6 1460.4406; found 1460.4373. Racemic Hexa(4-chlorophenyl)-2,6-helic[6]arene rac-5f. Following the same synthetic method of rac-5a, rac-5f as a white solid was obtained (33.0 mg, 58% yield). Mp > 300 °C; 1H NMR (500 MHz; acetone-d6) δ 7.65 (d, J = 7.0 Hz 6H), 7.52 (d, J = 7.0 Hz 6H), 7.40−7.26 (m, 18H), 7.19−7.16 (m, 6H), 6.90−6.87 (m,, 6H), 6.78 (s, 6H), 4.96 (s, 6H), 3.71 (s, 6H); 13C NMR (125 MHz, acetone-d6) δ 148.0, 146.4, 142.7, 136.3, 134.9, 133.1, 132.9, 132.3, 128.9, 128.8, 125.5, 124.6, 124.1, 122.9, 50.7; HRMS (APCI) m/z: [M + H]+ calcd for C99H61Cl6O6 1558.2603; found 1558.2595. (+)-P-Hexaphenyl-2,6-helic[6]arene (+)-P-5a. A mixture of rac-4 (50 mg, 0.037 mmol), K2CO3 (100 mg, 0.73 mmol), phenylboronic acid (45 mg, 0.37 mmol), and Pd(PPh3)4 (4 mg, 0.0037 mmol) was dissolved in toluene/ethanol/water (4.5 mL, 4:4:1, v/v/v) in a Schlenk tube. The mixture was stirred at 80 °C in oil bath for 12 h under N2 atmosphere and then quenched with water. The reaction mixture was extracted by ethyl acetate. The organic layer was separated, washed with brine for three times, and then dried over anhydrous MgSO4. The organic layer was evaporated and purified by column chromatography on silica gel (petroleum ether/dichloromethane, 1:3, v/v) to afford rac-5a (31.1 mg, 63% yield) as a white solid. Mp > 300 °C; [α]D25 = +184° (c = 0.5, CH2Cl2); 1H NMR (500 MHz, acetone-d6) δ 7.62 (t, J = 6.9 Hz, 6H), 7.59−7.49 (m, 12H), 7.44 (d, J = 6.9 Hz, 6H), 7.30 (d, J = 7.4 Hz, 6H), 7.26 (s, 6H), 7.14−7.13 (m, 6H), 6.99−6.88 (m, 6H), 6.22 (s, 6H), 4.95 (s, 6H), 3.68 (s, 6H); 13C NMR (125 MHz, acetone-d6) δ 148.7, 147.7, 143.5, 137.2, 136.7, 132.1, 131.3, 130.0, 129.7, 128.6, 126.1, 125.9, 125.4, 124.9, 123.7 51.7; HRMS (APCI) m/z: [M + H]+ calcd for C99H67O6 1352.4971; found 1352.5000. (+)-P-Hexa(4-methoxylphenyl)-2,6-helic[6]arene (+)-P-5b. Following the same synthetic method of (+)-P-5a, (+)-P-5b as a white solid was obtained (38.6 mg, 69% yield). Mp > 300 °C; [α]D25 = +234° (c = 0.5, CH2Cl2); 1H NMR (400 MHz; acetone-d6) 11538

DOI: 10.1021/acs.joc.8b01437 J. Org. Chem. 2018, 83, 11532−11540

Article

The Journal of Organic Chemistry Notes

(d, J = 6.8 Hz, 6H), 6.88−6.85 (m, 6H), 6.16 (s, 6H), 4.95 (s, 6H), 3.93 (s, 18H), 3.66 (s, 6H); 13C NMR (100 MHz, acetone-d6) δ 160.3, 148.9, 147.7, 143.8, 137.2, 133.5, 132.3, 128.5, 126.0, 125.4, 124.6, 123.7, 115.5, 115.1, 55.7, 51.8; HRMS (APCI) m/z: [M + H] + calcd for C105H79O12 1532.5605; found 1532.5597. (−)-M-Hexa(4-methylphenyl)-2,6-helic[6]arene (−)-M-5c. Following the same synthetic method of (−)-M-5a, (−)-M-5c as a white solid was obtained (34.1 mg, 65% yield). Mp > 300 °C; [α]D25 = −246° (c = 0.5, CH2Cl2); 1H NMR (500 MHz; acetone-d6) δ 7.45 (d, J = 7.4 Hz, 6H), 7.27 (s, 6H), 7.26−7.19 (m, 18H), 7.12−7.11 (m, 6H), 6.87−6.86 (m, 6H), 6.11 (s, 5H), 4.98 (s, 6H), 3.68 (s, 6H), 2.52 (s, 18H); 13C NMR (125 MHz, acetone-d6) δ 148.7, 147.6, 143.6, 137.9, 137.2, 133.5, 132.2, 130.8, 130.3, 126.1, 126.7, 125.4, 124.6, 123.7, 51.7, 21.5; HRMS (APCI) m/z: [M + H]+ calcd for C105H79O6 1436.5910; found 1436.5913. (−)-M-Hexa(4-ethylphenyl)-2,6-helic[6]arene (−)-M-5d. Following the same synthetic method of (−)-M-5a, (−)-M-5d as a white solid was obtained (38.9 mg, 70% yield). Mp > 300 °C; [α]D25 = −156° (c = 0.5, CH2Cl2); 1H NMR (500 MHz; acetone-d6): δ 7.48 (d, J = 7.6 Hz, 6H), 7.35 (d, J = 7.7 Hz, 6H), 7.31 (d, J = 7.7 Hz, 6H), 7.29−7.23 (m, 12H), 7.13−7.11 (m, 6H), 6.88−6.86 (m, 6H), 6.09 (s, 6H), 4.98 (s, 6H), 3.67 (s, 6H), 2.83 (q, J = 7.7 Hz, 12H), 1.41 (t, J = 7.6 Hz, 18H); 13C NMR (125 MHz, acetone-d6) δ 147.8, 146.7, 143.4, 142.7, 136.4, 132.9, 131.4, 130.2, 128.6, 128.2, 125.2, 124.9, 124.5, 123.8, 122.8, 50.8, 15.2; HRMS (APCI) m/z: [M + H]+ calcd for C111H91O6 1520.6849; found 1520.6844. (−)-M-Hexa(4-fluorophenyl)-2,6-helic[6]arene (−)-M-5e. Following the same synthetic method of (−)-M-5a, (−)-M-5e as a white solid was obtained (29.9 mg, 56% yield). Mp > 300 °C; [α]D25 = −160° (c = 0.5, CH2Cl2); 1H NMR (500 MHz; acetone-d6) δ 7.44−7.24 (m, 30H), 7.16−7.14 (m, 6H), 6.89−6.87 (m, 6H), 6.64 (s, 6H), 4.90 (s, 6H), 3.68 (s, 6H); 13C NMR (125 MHz, acetone-d6) δ 164.4, 162.4, 149.0, 147.4, 143.8, 137.1, 134.1, 133.4, 133.1, 126.3, 125.5, 125.1, 123.8, 116.5, 51.6; HRMS (APCI) m/z: [M + H] + calcd for C99H61F6O6 1460.4406; found 1460.4373. (−)-M-Hexa(4-chlorophenyl)-2,6-helic[6]arene (−)-M-5f. Following the same synthetic method of (−)-M-5a, (−)-M-5f as a white solid was obtained (33.0 mg, 58% yield). Mp > 300 °C; [α]D25 = −255° (c = 0.5, CH2Cl2); 1H NMR (500 MHz; acetone-d6) δ 7.65 (d, J = 7.0 Hz 6H), 7.52 (d, J = 7.0 Hz 6H), 7.40−7.26 (m, 18H), 7.19−7.17 (m, 6H), 6.90−6.87 (m, 6H), 6.78 (s, 6H), 4.96 (s, 6H), 3.71 (s, 6H); 13C NMR (125 MHz, acetone-d6) δ 148.0, 146.4, 142.7, 136.3, 134.9, 133.1, 132.9, 132.3, 128.9, 128.8, 125.5, 124.6, 124.1, 122.9, 50.7; HRMS (APCI) m/z: [M + H]+ calcd for C99H61Cl6O6 1558.2603; found 1558.2595.

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The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We thank the National Natural Science Foundation of China (21332008, 91527301, 21521002) and the Strategic Priority Research Program of CAS (XDB12010400) for financial support.

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ASSOCIATED CONTENT

* Supporting Information S

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.8b01437. Copies of 1H and 13C NMR spectra for new compounds; SEC traces of (−)-M-2; UV−vis and fluorescence spectra of rac-5a−f; CD spectra of (+)-P-5a−f and (−)-M-5a−f (PDF) Crystallographic data for compound rac-2 (CIF) Crystallographic data for compound rac-3 (CIF) Crystallographic data for compound (+)-P-4 (CIF) Crystallographic data for compound rac-5a (CIF)

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REFERENCES

(1) (a) Gutsche, C. D. Calixarenes Reisited Monographs in Supramolecular Chemistry; Royal Society of Chemistry: Cambridge, 1998. (b) Asfari, M. Z.; Böhmer, V.; Harrowfield, J.; Vicens, J. Calixarenes 2001; Kluwer Academic Publishers: Dordrecht, Holland, 2001. (c) Neri, P.; Sessler, J. L.; Wang, M.-X. Calixarenes and Beyond; Springer: Switzerland, 2016. (d) Guo, D. S.; Liu, Y. Calixarene-Based Supramolecular Polymerization in Solution. Chem. Soc. Rev. 2012, 41, 5907−5921. (2) (a) Biros, S. M.; Rebek, J., Jr. Structure and Binding Properties of Water-Soluble Cavitands and Capsules. Chem. Soc. Rev. 2007, 36, 93− 104. (b) Kobayashi, K.; Yamanaka, M. Self-Assembled Capsules Based on Tetrafunctionalized Calix[4]resorcinarene Cavitands. Chem. Soc. Rev. 2015, 44, 449−466. (3) (a) Hardie, M. J. Recent Advances in the Chemistry of Cyclotriveratrylene. Chem. Soc. Rev. 2010, 39, 516−527. (b) Yu, J.-T.; Huang, Z.-T.; Zheng, Q.-Y. Synthesis, Structure, Fullerene-Binding and Resolution of C3-Symmetric Cavitands with Rigid and Deep Cavities. Org. Biomol. Chem. 2012, 10, 1359−1364. (4) (a) Ogoshi, T.; Kanai, S.; Fujinami, S.; Yamagishi, T. A.; Nakamoto, Y. para-Bridged Symmetrical Pillar[5]arenes: Their Lewis Acid Catalyzed Synthesis and Host-Guest Property. J. Am. Chem. Soc. 2008, 130, 5022−5023. (b) Xue, M.; Yang, Y.; Chi, X.; Zhang, Z.; Huang, F. Pillararenes, A New Class of Macrocycles for Supramolecular Chemistry. Acc. Chem. Res. 2012, 45, 1294−1308. (c) Cragg, P. J.; Sharma, K. Pillar[5]arenes: Fascinating Cyclophanes with a Bright Future. Chem. Soc. Rev. 2012, 41, 597−607. (d) Strutt, N. L.; Zhang, H.; Schneebeli, S. T.; Stoddart, J. F. Functionalizing Pillar[n]arenes. Acc. Chem. Res. 2014, 47, 2631−2642. (e) Ogoshi, T.; Yamagishi, T. A.; Nakamoto, Y. Pillar-Shaped Macrocyclic Hosts Pillar[n]arenes: New Key Players for Supramolecular Chemistry. Chem. Rev. 2016, 116, 7937−8002. (5) Chen, H. Q.; Fan, J. Z.; Hu, X. S.; Ma, J. W.; Wang, S. L.; Li, J.; Yu, Y. H.; Jia, X. S.; Li, C. J. Biphen[n]arenes. Chem. Sci. 2015, 6, 197−202. (6) (a) Georghiou, P. E.; Ashram, M.; Clase, H. J.; Bridson, J. N. Spirodienone and Bis(spirodienone) Derivatives of Calix[4]naphthalenes. J. Org. Chem. 1998, 63, 1819−1826. (b) Tian, X.-H.; Hao, H.; Liang, T.-L.; Chen, C.-F. Triptycene-Derived Calix[6]arenes: Synthesis, Structure and Tubular Assemblies in the Solid State. Chem. Commun. 2009, 6771−6773. (c) Tian, X.-H.; Chen, C.F. Triptycene-Derived Calix[6]arenes: Synthesis, Structures, and Their Complexation with Fullerenes C60 and C70. Chem. - Eur. J. 2010, 16, 8072−8079. (d) Tian, X.-H.; Chen, C.-F. Synthesis, Structures, and Conformational Characteristics of Triptycene-Derived Calix[5]arenes. Org. Lett. 2010, 12, 524−527. (e) Li, P.-F.; Chen, C.F. Triptycene-Derived Calix[6]resorcinarene-Like Hosts: Synthesis, Structure and Self-Assemblies in the Solid State. Chem. Commun. 2011, 47, 12170−12172. (7) (a) Sun, Y.; Zhang, F.; Zhang, L.; Luo, L.; Zou, Z.-L.; Cao, X.-L.; Tan, S.-L.; Bi, J.-H.; Tian, D.-M.; Li, H.-B. Synthesis of Calix[4]arene Derivatives via a Pd-Catalyzed Sonogashira Reaction and Their Recognition Properties Towards Phenols. Chin. Chem. Lett. 2014, 25, 226−228. (b) Yeung, M. C.-L.; Yam, V. Luminescent Cation Sensors: From Host-Guest Chemistry, Supramolecular Chemistry to ReactionBased Mechanisms. Chem. Soc. Rev. 2015, 44, 4192−4202. (c) Zhang, D.; Martinez, A.; Dutasta, J.-P. Emergence of Hemicryptophanes: From Synthesis to Applications for Recognition, Molecular Machines, and Supramolecular Catalysis. Chem. Rev. 2017, 117, 4900−4942.

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Chuan-Feng Chen: 0000-0002-4347-1406 Author Contributions #

These authors contributed equally to this work. 11539

DOI: 10.1021/acs.joc.8b01437 J. Org. Chem. 2018, 83, 11532−11540

Article

The Journal of Organic Chemistry (8) (a) Zhang, X.; Wang, C. Supramolecular Amphiphiles. Chem. Soc. Rev. 2011, 40, 94−101. (b) Avestro, A.-J.; Belowich, M. E.; Stoddart, J. F. Cooperative Self-Assembly: Producing Synthetic Polymers with Precise and Concise Primary Structures. Chem. Soc. Rev. 2012, 41, 5881−5895. (c) Jie, K.; Zhou, Y.; Yao, Y.; Huang, F. Macrocyclic Amphiphiles. Chem. Soc. Rev. 2015, 44, 3568−3587. (9) (a) Raynal, M.; Ballester, P.; Vidal-Ferran, A.; van Leeuwen, P. Supramolecular Catalysis. Part 1: Non-Covalent Interactions as a Tool for Building and Modifying Homogeneous Catalysts. Chem. Soc. Rev. 2014, 43, 1660−1733. (b) Raynal, M.; Ballester, P.; Vidal-Ferran, A.; van Leeuwen, P. Supramolecular Catalysis. Part 2: Artificial Enzyme Mimics. Chem. Soc. Rev. 2014, 43, 1734−1787. (10) (a) Dondoni, A.; Marra, A. Calixarene and Calixresorcarene Glycosides: Their Synthesis and Biological Applications. Chem. Rev. 2010, 110, 4949−4977. (b) Miyata, K.; Nishiyama, N.; Kataoka, K. Rational Design of Smart Supramolecular Assemblies for Gene Delivery: Chemical Challenges in the Creation of Artificial Viruses. Chem. Soc. Rev. 2012, 41, 2562−2574. (c) Nimse, S. B.; Kim, T. Biological Applications of Functionalized Calixarenes. Chem. Soc. Rev. 2013, 42, 366−386. (d) Zhou, Y.; Li, H.; Yang, Y.-W. Controlled Drug Delivery Systems Based on Calixarenes. Chin. Chem. Lett. 2015, 26, 825−828. (e) Feng, Z.; Zhang, T.; Wang, H.; Xu, B. Supramolecular Catalysis and Dynamic Assemblies for Medicine. Chem. Soc. Rev. 2017, 46, 6470−6479. (11) (a) Descalzo, A. B.; Martinez-Manez, R.; Sancenon, F.; Hoffmann, K.; Rurack, K. The Supramolecular Chemistry of OrganicInorganic Hybrid Materials. Angew. Chem., Int. Ed. 2006, 45, 5924− 5948. (b) Mines, G. A.; Tzeng, B.-C.; Stevenson, K. J.; Li, J.; Hupp, J. T. Microporous Supramolecular Coordination Compounds as Chemosensory Photonic Lattices. Angew. Chem., Int. Ed. 2002, 41, 154−157. (12) (a) Kinbara, K.; Hashimoto, Y.; Sukegawa, M.; Nohira, H.; Saigo, K. Crystal Structures of the Salts of Chiral Primary Amines with Achiral Carboxylic Acids: Recognition of the Commonly-Occurring Supramolecular Assemblies of Hydrogen-Bond Networks and Their Role in the Formation of Conglomerates. J. Am. Chem. Soc. 1996, 118, 3441−3449. (b) Mateos-Timoneda, M. A.; Crego-Calama, M.; Reinhoudt, D. N. Supramolecular Chirality of Self-assembled Systems in Solution. Chem. Soc. Rev. 2004, 33, 363−372. (c) Miyauchi, M.; Takashima, Y.; Yamaguchi, H.; Harada, A. Chiral Supramolecular Polymers Formed by Host-Guest Interactions. J. Am. Chem. Soc. 2005, 127, 2984−2989. (d) Luo, J.; Zheng, Y. Chiral Calixarenes and Their Supramolecular Chirality. Prog. Chem. 2018, 30, 601−615. (13) (a) Kubo, Y.; Maeda, S. Y.; Tokita, S.; Kubo, M. Colorimetric Chiral Recognition by a Molecular Sensor. Nature 1996, 382, 522− 524. (b) Casnati, A.; Sansone, F.; Ungaro, R. Peptido- and Glycocalixarenes: Playing with Hydrogen Bonds around Hydrophobic Cavities. Acc. Chem. Res. 2003, 36, 246−254. (c) Baldini, L.; Casnati, A.; Sansone, F.; Ungaro, R. Calixarene-Based Multivalent Ligands. Chem. Soc. Rev. 2007, 36, 254−266. (14) (a) Brotin, T.; Dutasta, J. P. Cryptophanes and Their Complexes-Present and Future. Chem. Rev. 2009, 109, 88−130. (b) Szumna, A. Inherently Chiral Concave MoleculesFrom Synthesis to Applications. Chem. Soc. Rev. 2010, 39, 4274−4285. (c) 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. (d) Xu, Z.-X.; Zhang, C.; Zheng, Q.-Y.; Chen, C.-F.; Huang, Z.-T. A New Approach to Enantiopure Inherently Chiral Calix[4]arenes: Determination of Their Absolute Configurations. Org. Lett. 2007, 9, 4447−4450. (e) Xu, Z.-X.; Zhang, C.; Yang, Y.; Chen, C.-F.; Huang, Z.-T. Effective Nonenzymatic Kinetic Resolution of Racemic m-Nitro-Substituted Inherently Chiral Aminocalix[4]arenes. Org. Lett. 2008, 10, 477−479. (f) Arnott, G. E. Inherently Chiral Calixarenes: Synthesis and Applications. Chem. - Eur. J. 2018, 24, 1744−1754. (15) (a) Ogoshi, T.; Kitajima, K.; Aoki, T.; Yamagishi, T. A.; Nakamoto, Y. Effect of an Intramolecular Hydrogen Bond Belt and Complexation with the Guest on the Rotation Behavior of Phenolic

Units in Pillar[5]arenes. J. J. Phys. Chem. Lett. 2010, 1, 817−821. (b) Ogoshi, T.; Akutsu, T.; Yamafuji, D.; Aoki, T.; Yamagishi, T. A. Solvent-and Achiral-Guest-Triggered Chiral Inversion in a Planar Chiral pseudo[1]Catenane. Angew. Chem., Int. Ed. 2013, 52, 8111− 8115. (c) Strutt, N. L.; Zhang, H.; Stoddart, J. F. Enantiopure Pillar[5]arene Active Domains within a Homochiral Metal-organic Framework. Chem. Commun. 2014, 50, 7455−7458. (d) Ogoshi, T.; Furuta, T.; Yamagishi, T. A. Chiral Supramolecular Polymers Consisting of Planar-chiral Pillar[5]arene Enantiomers. Chem. Commun. 2016, 52, 10775−10778. (e) Yao, J.; Wu, W.; Liang, W.; Feng, Y.; Zhou, D.; Chruma, J. J.; Fukuhara, G.; Mori, T.; Inoue, Y.; Yang, C. Temperature-Driven Planar Chirality Switching of a Pillar[5]arene-Based Molecular Universal Joint. Angew. Chem., Int. Ed. 2017, 56, 6869−6873. (16) Zhang, G.-W.; Li, P.-F.; Meng, Z.; Wang, H.-X.; Han, Y.; Chen, C.-F. Triptycene-Based Chiral Macrocyclic Hosts for Highly Enantioselective Recognition of Chiral Guests Containing a Trimethylamino Group. Angew. Chem., Int. Ed. 2016, 55, 5304−5308. (17) (a) Shi, Q.; Han, Y.; Chen, C.-F. Complexation Between (OMethyl)6-2,6-Helic[6]arene and Tertiary Ammonium Salts: Acid/ Base-or Chloride-Ion-Responsive Host-Guest Systems and Synthesis of [2]Rotaxane. Chem. - Asian J. 2017, 12, 2576−2582. (b) Zhang, G.W.; Shi, Q.; Chen, C.-F. Formation of Charge-transfer Complexes Based on a Tropylium Cation and 2,6-Helic[6]arenes: A Visible Redox Stimulus-Responsive Process. Chem. Commun. 2017, 53, 2582−2585. (c) Zhang, G.-W.; Han, Y.; Wang, Y.-L.; Chen, C.-F.; Han, Y. Synthesis of a Water-soluble 2,6-helic[6]arene Derivative and Its Strong Binding Abilities towards Quaternary Phosphonium Salts: An Acid/base Controlled Switchable Complexation Process. Chem. Commun. 2017, 53, 10433−10436. (d) Shi, Q.; Chen, C.-F. Switchable Complexation between (O-Methyl)6-2,6-helic[6]arene and Protonated Pyridinium Salts Controlled by Acid/Base and Photoacid. Org. Lett. 2017, 19, 3175−3178. (e) Zhang, G.-W.; Li, P.F.; Wang, H.-X.; Han, Y.; Chen, C.-F. Complexation of Racemic 2,6Helic[6]arene and Its Hexamethyl-Substituted Derivative with Quaternary Ammonium Salts, N-Heterocyclic Salts, and Tetracyanoquinodimethane. Chem. - Eur. J. 2017, 23, 3735−3742. (18) Shi, Q.; Meng, Z.; Xiang, J.-F.; Chen, C.-F. Efficient Control of Movement in Non-Photoresponsive Molecular Machines by a PhotoInduced Proton-Transfer Strategy. Chem. Commun. 2018, 54, 3536− 3539. (19) Ogoshi, T.; Aoki, T.; Kitajima, K.; Fujinami, S.; Yamagishi, T. A.; Nakamoto, Y. Facile, Rapid, and High-Yield Synthesis of Pillar[5]arene from Commercially Available Reagents and Its X-ray Crystal Structure. J. Org. Chem. 2011, 76, 328−331. (20) (a) Jin, Y. H.; Yu, C.; Denman, R. J.; Zhang, W. Recent Advances in Dynamic Covalent Chemistry. Chem. Soc. Rev. 2013, 42, 6634−6654. (b) Ogoshi, T.; Ueshima, N.; Akutsu, T.; Yamafuji, D.; Furuta, T.; Sakakibara, F.; Yamagishi, T. A. The Template Effect of Solvents on High Yield Synthesis, Co-cyclization of Pillar[6]arenes and Interconversion between Pillar[5]- and Pillar[6]arenes. Chem. Commun. 2014, 50, 5774−5777.

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DOI: 10.1021/acs.joc.8b01437 J. Org. Chem. 2018, 83, 11532−11540