Synthesis of [2]Catenanes by Intramolecular Sonogashira-Type

DOI: 10.1021/acs.joc.7b00672. Publication Date (Web): May 18, 2017. Copyright © 2017 American Chemical Society. *E-mail: [email protected]...
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Synthesis of [2]Catenanes by Intramolecular Sonogashira-Type Reaction Ken Ito, Yuichiro Mutoh, and Shinichi Saito* Department of Chemistry, Faculty of Science, Tokyo University of Science, Kagurazaka, Shinjuku, Tokyo 162-8601, Japan S Supporting Information *

ABSTRACT: The catalytic activity of macrocyclic phenanthroline-CuI complexes was utilized to synthesize [2]catenanes by intramolecular Sonogashira-type reaction. The high reactivity of the acyclic starting material was critical to synthesize the [2]catenane in acceptable yields. The relationship between the yield of the [2]catenane and the structure of the starting materials was disclosed.

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INTRODUCTION [2]Catenane is a family of interlocked compounds which is composed of two ring components. The structure of catenanes has been utilized to observe stimuli-triggered motions of the ring components, and these properties would be important for the future development of molecular devices with specific functions. To achieve this goal, the chemistry of catenane has been extensively studied, and various methods have been developed for the synthesis of catenanes.1 Recently, we reported a new method to synthesize [2]catenanes. The catalytic threading strategy, which was originally developed for the synthesis of [2]rotaxanes from macrocyclic phenanthrolineCu complexes,2 was applied to the synthesis of new [2]catenanes. The intramolecular Glaser coupling of α,ωdiynes proceeded in the presence of macrocyclic phenanthroline-Cu complexes and [2]catenanes were synthesized.3 A similar strategy for the synthesis of [2]catenanes was reported, where intramolecular Huisgen reaction and Cadiot−Chodkiewicz reaction were used as the cyclization reaction.4 These studies enabled the synthesis of [2]catenanes with new structures in acceptable yields. The coupling reactions employed for the cyclization reaction, however, are very limited in number, and the scope of this synthetic method remains to be established. Further development of a new approach for the synthesis of [2]catenanes would enrich the chemistry of interlocked compounds and provide a basis for the generation of molecules with various functions. We previously reported the synthesis of [2]rotaxanes by the Sonogashira-type reaction.2c,5 A macrocyclic phenanthrolineCu complex catalyzed the cross-coupling reaction of terminal alkyne and aryl iodides in the absence of a palladium catalyst.6 The Cu-mediated carbon−carbon bond formation reaction proceeded inside the ring, and [2]rotaxanes were synthesized in good yields (Scheme 1). A 2-iodobenzoate was a suitable substrate for the Sonogashira-type reaction. Recently, Collins and co-workers reported that the intramolecular Sonogashira© 2017 American Chemical Society

Scheme 1. Synthesis of a [2]Rotaxane by Sonogashira-Type Reaction (Ref 2c)

type reaction proceeded in the presence of phenanthroline and CuCl, and macrocyclic compounds were synthesized.7 These studies prompted us to examine the synthesis of [2]catenanes by intramolecular Sonogashira-type reaction. Herein, we report the synthesis of [2]catenanes utilizing the catalytic activity of macrocyclic phenanthroline-Cu complex for the Sonogashiratype reaction.

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RESULTS AND DISCUSSION Cu-Mediated Intramolecular Sonogashira-Type Reaction of 2 and 5. We synthesized 2-iodobenzoate 2 as a substrate for the synthesis of [2]catenanes and studied the reactivity of 2 in the presence of copper catalysts (Scheme 2a,b). The cyclization of 2 proceeded smoothly when the reaction was conducted under the conditions described by Collins et al.7 Thus, compound 2 cyclized in the presence of phenanthroline (0.20 equiv), CuCl (0.05 equiv), and Cs2CO3 Received: March 21, 2017 Published: May 18, 2017 6118

DOI: 10.1021/acs.joc.7b00672 J. Org. Chem. 2017, 82, 6118−6124

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The Journal of Organic Chemistry

isolated in 19% yield (entry 1). The yield of 7 increased to 29% when the reaction was carried out under at lower concentration ([1A-CuI] = 3.0 mM) and the reaction time was set to 48 h (entry 2). When a larger amount of 5 (5.0 equiv) was used as the substrate, the yield of 7 did not significantly increase (33% yield, entry 3). Synthesis of [2]Catenanes from Aromatic Alkyne. In order to increase the yield of [2]catenane, we next examined the relationship between the structure of the alkyne and the yield of [2]catenane. We synthesized ethynylbenzene derivatives (8a−c) as the substrates and studied the synthesis of [2]catenane (Table 2). When the ortho isomer 8a (2.2 equiv)

Scheme 2. Cu-Mediated Intramolecular Sonogashira-Type Reaction of 2 and 5

Table 2. Synthesis of [2]Catenanes from Aromatic Alkyne 8

(2.0 equiv) at 135 °C in toluene under diluted condition ([2] = 24 mM) and the product 3 was isolated in 59% yield. The cyclization of 2, however, did not proceed in the presence of diarylphenanthroline-CuI complex 4 (0.45 equiv) and K2CO3 (2.0 equiv)8 in xylene ([2] = 24 mM) at 135 °C. We assumed that the low catalytic activity of 4 under diluted condition9 would be responsible for this unsuccessful result. In order to overcome this problem, we examined the cyclization of a more reactive substrate 510 (Scheme 2c). When a mixture of 5 (1.0 equiv), diarylphenanthroline-CuI complex 4 (0.45 equiv), and K2CO3 (2.0 equiv) was stirred in xylene at 120 °C for 24 h, the cyclization product 6 was isolated in 20% yield (Scheme 2c). Synthesis of [2]Catenane by Intramolecular Sonogashira-Type Reaction. With this successful result in hand, we synthesized [2]catenanes by the intramolecular Sonogashiratype reaction. The results are summarized in Table 1. The cyclization of 5 proceeded in the presence of macrocyclic phenanthroline-CuI complex 1A-CuI (1.0 equiv) and K2CO3 (4.0 equiv) in xylene under dilute condition ([1A-CuI] = 8.0 mM) at 120 °C for 24 h. The mixture was treated with aqueous NH3 to remove the copper ion,11 and the [2]catenane 7 was

a

was used as substrate, the reaction completed in 72 h and the yield of the [2]catenane 9aa was very low (16%, entry 1). The meta isomer 8b was a better substrate, the reaction completed in a shorter period (24 h) and [2]catenane 9Ab was isolated in 30% yield (entry 2). Though the reaction of the para isomer 8c proceeded, the yield of [2]catenane 9Ac did not improve (13%, entry 3). Based on these results, we chose 8b as the best substrate for the synthesis of the [2]catenane. Effect of the Size of the Macrocyclic PhenanthrolineCuI Complex on the Yield of [2]Catenane. We next examined the reaction of macrocyclic phenanthroline-CuI complex with different size (Table 3). When a smaller macrocyclic complex 1A-CuI reacted with a small excess (5.0 equiv) of 8b under dilute condition ([1A-CuI] = 1.8 mM), the [2]catenane 9Ab was isolated in 50% yield. As opposed to the result of the reaction of 5 (Table 1, entry 3), the use of an increased amount of 8b as the substrate resulted in the significantly increased yield of the [2]catenane. The improved yield of the [2]catenane in the presence of a larger amount of 8b can be explained by supposing that the macrocyclic phenanthroline-CuI complex was regenerated when the formation of [2]catenane 9Ab failed.3 The reaction of 8b with a larger macrocyclic complex (1B-CuI) completed in a shorter period (48 h) and yield of the [2]catenane 9Bb increased (64% yield, entry 2). Though we expected that the

Table 1. Synthesis of [2]Catenanes by Intramolecular Sonogashira-Type Reaction

entry

5 (equiv)

K2CO3 (equiv)

conc. of 1A-CuI (mM)

time (h)

yielda (%)

1 2 3

2.2 2.2 5.0

4.0 4.0 9.0

8.0 3.0 3.0

24 48 144

19 29 33

a

Isolated yield.

Isolated yield. 6119

DOI: 10.1021/acs.joc.7b00672 J. Org. Chem. 2017, 82, 6118−6124

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The Journal of Organic Chemistry Table 3. Effect of the Size of the Macrocyclic Phenanthroline-CuI Complex on the Yield of [2]Catenane

a

entry

1-CuI

time (h)

[2]catenane

yielda (%)

1 2 3

1A-CuI (n = 6) 1B-CuI (n = 8) 1C-CuI (n = 10)

72 48 48

9Ab (n = 6) 9Bb (n = 8) 9Cb (n = 10)

50 64 24

Isolated yield.

yield of the [2]catenane would increase by using a larger complex (1C-CuI), the corresponding [2]catenane 9Cb was isolated in low yield (24%, entry 3). Effect of the Length of the Acyclic Starting Material on the Yield of the yield of [2]Catenane. We also examined the effect of the length of the acyclic starting materials on the yield of [2]catenane. The results are summarized in Table 4. As described in Table 3 (entry 1), a

Figure 1. 1H NMR spectra of [2]catenane 9Ab and related compounds (500 MHz, CDCl3, 298 K).

Table 4. Effect of the Length of the Acyclic Starting Material on the Yield of [2]Catenane

a

entry

alkyne

m

[2]catenane

yield (%)a

1 2 3

8b 8d 8e

20 15 12

9Ab 10 11

50 48 0

Hb and Ho shifted downfield (Δδ = +0.06 ppm (Hb), +0.18 ppm (Ho)) in 9Ab. The observed downfield shifts of Hb and Ho would be explained in terms of the location of these protons: unlike other protons, Hb and Ho are situated inside the ring component, and the conversion of the macrocyclic ring into the [2]catenane induced the downfield shifts of these protons. The observed difference of the chemical shifts is in accordance with those of the structurally related interlocked compounds we previously reported.2

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CONCLUSION We succeeded in the synthesis of [2]catenanes by intramolecular Sonogashira-type reaction, which was mediated by the macrocyclic phenanthroline-CuI complex. The reactivity of the acyclic starting materials was important to synthesize the [2]catenane in good yield. Further studies related to the synthesis of complex interlocked compounds based on this approach will be reported in due course.

Isolated yield.

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substrate with a long methylene chain (m = 20, 8b) gave [2]catenane 9Ab in 50% yield (Table 4, entry 1). The yield of [2]catenane 10, which was synthesized from an iodide with a shorter methylene chain (m = 15, 8d) was comparable to that of 9Ab (48%, entry 2). When an iodide with a very short methylene chain (8e, m = 12) was used as the starting material, the corresponding [2]catenane 11 was not isolated (entry 3).12 Comparison of the 1H NMR Spectra of [2]Catenane and Related Compounds. The 1H NMR spectra of [2]catenane 9Ab and related compounds are shown in Figure 1. Compared to the signals of the ring components (1A and 12), many signals shifted upfield in the NMR spectrum of the [2]catenane 9Ab. For example, the signals of the resorcinol moiety (Ha,c) and p-anisyl moiety (Hd,e) of 1A shifted upfield (Δδ = −0.07 ppm (Ha,c), −0.06 ppm (Hd), −0.05 ppm (He)) in the NMR spectrum of 9Ab. On the other hand, the signals of

EXPERIMENTAL SECTION

Reagents were commercially available and used without further purification unless otherwise noted. NMR spectra were recorded using a 300 MHz/76 MHz (1H NMR/13C NMR) or a 500 MHz/126 MHz (1H NMR/13C NMR) spectrometer. Chemical shifts were reported in delta units (δ) relative to chloroform (7.24 ppm for 1H NMR and 77.0 ppm for 13C NMR) and DMSO-d5 (2.50 ppm for 1H NMR and 39.5 ppm for 13C NMR). A YMC T30000 column (eluent: CHCl3) was used for GPC (gel permeation chromatography) separation. Column chromatography was performed using Kanto Chemical silica gel 60N (spherical, neutral 63-210 m). Flash column chromatography was performed using Kanto Chemical silica gel 60N (spherical, neutral 40− 50 μm). Preparative thin layer chromatography (PTLC) was performed using a Merck silica gel 60 plate. High-resolution mass spectra (HR-MS) were obtained by a quadrupole mass analyzer. 22-(Methoxymethoxy)docos-1-yne (S2). To a solution of 1bromo-20-(methoxymethoxy)icosane2e (S1, 0.14 g, 0.28 mmol) in dry 6120

DOI: 10.1021/acs.joc.7b00672 J. Org. Chem. 2017, 82, 6118−6124

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The Journal of Organic Chemistry

temperature was kept at −78 °C for 15 min, and then the reaction mixture was allowed to warm to room temperature and stirred for overnight. After the addition of cold water, the mixture was extracted with AcOEt. The combined organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel, hexane−AcOEt (5/1(v/v)) as the eluent) to afford S5 (0.93 g, 2.56 mmol, 94%) as a white solid; mp 231.0− 232.2 °C; 1H NMR (300 MHz, DMSO-d6):δ 9.39 (s, 1H), 7.26 (dd, J = 7.9, 1.4 Hz, 1H), 7.02 (ddd, J = 7.2, 7.2, 1.8 Hz, 1H), 6.89−6.84 (m, 3H), 6.71 (t, J = 7.2 Hz, 1H), 6.10 (d, J = 8.6 Hz, 2H); 13C NMR (125 MHz, DMSO-d6):δ 174.0, 164.6, 159.9, 155.3, 134.6, 131.5, 126.0, 125.6, 125.3, 119.3, 118.0, 114.9, 87.5; IR (ATR) 3168, 1604, 1500, 1464, 1332, 1280, 1270, 1214, 1167 cm−1; HR-MS (ESI) Calcd for C15H9O3I ([M−H]−): 362.9524. Found: 362.9524. 2-(4-(Docos-21-yn-1-yloxy)phenyl)-3-iodo-4H-chromen-4-one (5). A mixture of S3 (0.042 g, 0.13 mmol) and diethyl azodicarboxylate (40% toluene solution, 0.10 mL) in dry THF (0.40 mL) was added to a solution of S5 (0.070 g, 0.20 mmol) and PPh3 (0.052 g, 0.20 mmol) in dry THF (1.0 mL). The mixture was refluxed under Ar atmosphere for overnight. The solvent was removed in vacuo, and the residue was purified by flash column chromatography (silica gel, using hexane− AcOEt (10/1(v/v)) as the eluent) to afford 5 (0.81 g, 0.12 mmol, 93%) as a white solid; mp 81.8−83.0 °C; 1H NMR (300 MHz, CDCl3):δ 8.26 (dd, J = 8.1, 1.5 Hz, 1H), 7.77 (d, J = 8.6 Hz, 2H), 7.68 (ddd, J = 6.6, 6.6, 1.8 Hz, 1H), 7.44−7.42 (m, 3H), 6.99 (d, J = 8.6 Hz, 2H), 4.02 (t, J = 6.5 Hz, 2H), 2.15 (t, J = 7.0 Hz, 2H), 1.91 (s, 1H), 1.83−1.24 (m, 2H), 1.46−1.30 (m, 34H); 13C NMR (125 MHz, CDCl3):δ 174.7, 164.4, 161.3, 155.8, 134.0, 131.3, 126.8, 126.73, 125.7, 120.0, 117.5, 114.0, 87.5, 84.8, 68.2, 68.0, 29.7, 29.59, 29.57, 29.5, 29.4, 29.3, 29.13, 29.11, 28.8, 28.5, 26.0, 18.4; IR (ATR) 3307, 3064, 2915, 2850, 1650, 1609, 1554, 1506, 1468, 1350, 1330, 1254, 1184, 1060 cm−1; HR-MS (ESI) Calcd for C37H50IO3 [(M+H)+]: 669.2799. Found: 669.2797. Macrocycle (6). A mixture of 42c (0.013 g, 0.023 mmol), 5 (0.030 g, 0.046 mmol), and K2CO3 (0.013 g, 0.092 mmol) in dry xylene (1.1 mL) was stirred at 120 °C under Ar atmosphere. After stirring for 24 h, the solution was cooled to room temperature and the solvent was removed in vacuo. CH2Cl2 and H2O were added to the residue. The organic and aqueous layers were separated and the aqueous layer was extracted with CH2Cl2. The combined organic layer was washed with water, dried over Na2SO4, and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel, using hexane− AcOEt (6/1 (v/v)) as the eluent) to afford 6 (7.0 mg, 0.013 mmol, 20%) as a white solid; mp 43.0−44.1 °C; 1H NMR (500 MHz, CDCl3):δ 8.24−8.19 (m, 3H), 7.64 (ddd, J = 7.0, 7.0, 1.5 Hz, 1H), 7.47 (d, J = 4.0 Hz, 1H), 7.38 (t, J = 7.4 Hz, 1H), 6.98 (d, J = 9.2 Hz, 2H), 4.04 (t, J = 6.6 Hz, 2H), 2.50 (t, J = 7.2 Hz, 2H), 1.85−1.79 (m, 2H), 1.60−1.26 (m, 34H); 13C NMR (125 MHz, CDCl3):δ 177.3, 165.0, 161.6, 155.3, 133.6, 130.7, 126.1, 125.1, 124.6, 122.2, 117.8, 114.0, 106.4, 99.6, 72.8, 68.2, 29.54, 29.50, 29.3, 29.23, 29.21, 29.2, 29.10, 28.74, 28.71, 28.6, 28.5, 28.4, 28.2, 28.0, 27.8, 25.6, 20.2; IR (ATR) 2920, 2850, 1636, 1610, 1508, 1464, 1378, 1256, 1234, 1203, 1179 cm−1; HR-MS (ESI) Calcd for C37H49O3 [(M+H)+]: 541.3676. Found: 541.3670. [2]Catenane (7, Procedure A). A mixture of 1A-CuI2 (0.024 g, 0.029 mmol), 4 (0.042 g, 0.064 mmol), and K2CO3 (0.016 g, 0.11 mmol) in dry xylene ([1A-CuI] = 3.0 mM, 9.6 mL) under Ar atmosphere was stirred at 120 °C. After stirring for 24 h, the solution was cooled to room temperature and CH2Cl2, CH3CN, and NH3 aq. (30% solution, 5.0 mL) was added. After stirring at room temperature for overnight, the solution was extracted with CH2Cl2, dried over Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography (silica gel, using CH2Cl2 as the eluent) and GPC to afford 7 (0.010 g, 0.0084 mmol, 29%) as a yellow amorphous solid; 1H NMR (500 MHz, CDCl3):δ 8.42 (d, J = 8.6 Hz, 4H), 8.22− 8.20 (m, 5H), 8.05 (d, J = 8.6 Hz, 2H), 7.72 (s, 2H), 7.51 (ddd, J = 8.0, 8.0, 1.0 Hz, 1H), 7.45 (d, J = 3.7 Hz, 1H), 7.31 (t, J = 7.4 Hz, 1H), 7.09 (t, J = 8.3 Hz, 1H), 7.03 (d, J = 4.6 Hz, 2H), 6.99 (d, J = 8.6 Hz, 4H), 6.50 (s, 1H), 6.43 (dd, J = 8.0, 2.3 Hz, 2H), 3.97−3.95 (m, 6H), 3.92−3.90 (m, 4H), 2.43 (t, J = 8.0 Hz, 2H), 1.86−1.74 (m, 10H),

DMF (0.31 mL) was added sodium acetylide (18% in xylene, 0.12 mL, 0.43 mmol) under Ar atmosphere at 0 °C. The reaction mixture was stirred at room temperature for 24 h, and quenched with H2O. The mixture was extracted with CH2Cl2, dried over Na2SO4, and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel) using hexane−AcOEt (16/1 (v/v)) as an eluent to afford S2 (0.10 g, 0.28 mmol, quant) as a white solid; mp 38.7−39.9 °C; 1H NMR (300 MHz, CDCl3):δ 4.60 (s, 2H), 3.50 (t, J = 6.6 Hz, 2H), 3.34 (s, 3H), 2.16 (td, J = 7.0, 3.5 Hz, 2H), 1.92 (t, J = 2.6 Hz, 1H), 1.59−1.23 (m, 36H); 13C NMR (125 MHz, CDCl3):δ 96.4, 84.8, 68.0, 67.9, 55.1, 29.7, 29.67, 29.65, 29.60, 29.5, 29.1, 28.8, 28.5, 26.2, 18.9; IR (ATR) 3282, 2915, 2848, 1468, 1149, 1109, 1077, 1039 cm−1; HR-MS (ESI) Calcd for C24H47O2 [(M+H)+]: 367.3570. Found: 367.3571. Docos-21-yn-1-ol (S3). A mixture of S2 (0.86 g, 2.43 mmol) and conc. HCl aq. (12 M, 1.6 mL, 19 mmol) in THF (42 mL) and MeOH (21 mL) was refluxed for overnight. The solvent was removed in vacuo. The residue was purified by silica gel column chromatography using hexane−AcOEt (20/1 (v/v)) as the eluent afford to S3 (0.72 g, 2.2 mmol, 92%) as a white solid; mp 66.9−68.1 °C; 1H NMR (300 MHz, CDCl3):δ 3.61 (t, J = 6.6 Hz, 2H), 2.16 (td, J = 7.1, 2.6 Hz, 2H), 1.91 (t, J = 2.6 Hz, 1H), 1.57−1.19 (m, 36H); 13C NMR (125 MHz, CDCl3):δ 84.8, 68.0, 63.1, 32.8, 29.67, 29.64, 29.61, 29.5, 29.4, 29.1, 28.8, 28.5, 25.7, 18.4; IR (ATR) 3286, 2917, 2848, 1473, 1461, 1071 cm−1; HR-MS (ESI) Calcd for C22H43O [(M+H)+]: 323.3308. Found: 323.3314. Docos-21-yn-1-yl 2-iodobenzoate (2). A mixture of S3 (0.10 g, 0.31 mmol), 2-iodobenzoic acid (0.11 g, 0.46 mmol), DCC (0.12 g, 0.62 mmol), and DMAP (0.13 g, 0.93 mmol) in dry CH2Cl2 (3.0 mL) was stirred at room temperature overnight. The solution was added to water and extracted with CH2Cl2. The organic layer was dried over Na2SO4 and concentrated in vacuo. The reside was purified by flash column chromatography (silica gel, hexane−AcOEt (20/1 (v/v)) as the eluent) to afford 2 (0.15 g, 0.25 mmol, 83%) as a white solid; mp 52.6−53.7 °C; 1H NMR (300 MHz, CDCl3):δ 7.97 (dd, J = 7.9, 1.1 Hz, 1H), 7.76 (dd, J = 7.9, 1.7 Hz, 1H), 7.38 (td, J = 7.6, 1.0 Hz, 1H), 7.12 (td, J = 7.7, 1.6 Hz, 1H), 4.31 (t, J = 6.7 Hz, 2H), 2.16 (td, J = 7.0, 2.5 Hz, 2H), 1.91 (t, J = 2.6 Hz, 1H), 1.80−1.71 (m, 2H), 1.44−1.27 (m, 34H); 13C NMR (125 MHz, CDCl3):δ 166.7, 141.2, 135.6, 132.4, 130.8, 127.9, 94.0, 84.8, 68.0, 65.9, 29.67, 29.63, 29.6, 29.57, 29.5, 29.2, 29.1, 29.0, 28.8, 28.6, 28.5, 26.0, 18.4; IR (ATR) 3276, 2917, 2846, 1719, 1578, 1457, 1289, 1240, 1096, 1016, 734 cm−1; HR-MS (ESI) Calcd for C29H45O2INa [(M+Na)+]: 575.2356. Found: 575.2375. Synthesis of the Macrocycle (3). A reported procedure7 was followed to synthesize 3. To a mixture of CuCl (0.60 mg, 0.20 equiv), 1,10-phenanthroline (4.0 mg, 0.026 mmol), and Cs2CO3 (0.26 mmol, 0.093 g) was added a solution of 2 (0.074 g, 0.13 mmol) in dry toluene (5.5 mL, 24 mM). The reaction mixture was stirred in a sealed tube at 135 °C for 24 h. The mixture was cooled to room temperature and diluted with CH2Cl2. The resulting solution was filtered through a pad of Celite and was concentrated in vacuo. CH2Cl2 and H2O were added to the residue. The organic and aqueous layers were separated and the aqueous layer was extracted with CH2Cl2. The combined organic layer was washed with water, dried over Na2SO4, and concentrated in vacuo. The residue was purified by silica gel column chromatography using hexane−AcOEt (20/1 (v/v)) to afford product 3 as a white solid (0.033 g, 0.077 mmol, 59%); mp 43.0−44.1 °C; 1H NMR (300 MHz, CDCl3):δ 7.84 (dd, J = 7.7, 1.2 Hz, 1H), 7.47 (dd, J = 7.6, 1.4 Hz, 1H), 7.38 (td, J = 7.6, 1.5 Hz, 1H), 7.28 (td, J = 7.6, 1.4 Hz, 1H), 4.31 (t, J = 6.9 Hz, 2H), 2.42 (t, J = 7.2 Hz, 2H), 1.75 (t, J = 14.6 Hz, 2H), 1.64− 1.54 (m, 4H), 1.40−1.25 (m, 32H); 13C NMR (125 MHz, CDCl3):δ 167.1, 134.1, 132.6, 131.2, 130.1, 131.2, 130.1, 127.1, 124.0, 95.6, 79.3, 65.4, 29.1, 29.0, 28.99, 28.95, 28.9, 28.8, 28.73, 28.71, 28.44, 28.4, 28.1, 28.0, 27.7, 27.6, 25.9, 19.9; IR (ATR) 2924, 2844, 1698, 1595, 1462, 1444, 1287, 1247, 1126, 1040, 756 cm−1; HR-MS (ESI) Calcd for C29H44O2Na [(M+Na)+]: 447.3234. Found: 447.3213. 2-(4-Hydroxyphenyl)-3-iodo-4H-chromen-4-one (S5). To a solution of 2-(4-methoxyphenyl)-3-iodo-4H-chromen-4-one13 (S4, 1.0 g, 2.7 mmol) in dry CH2Cl2 (45 mL) was added BBr3 (1.0 M in CH2Cl2, 8.2 mL, 8.2 mmol) at −78 °C under Ar atmosphere. The 6121

DOI: 10.1021/acs.joc.7b00672 J. Org. Chem. 2017, 82, 6118−6124

Article

The Journal of Organic Chemistry 1.52−1.30 (m, 42H); 13C NMR (125 MHz, CDCl3):δ 177.3, 164.8, 161.5, 160.35, 160.3, 156.2, 155.3, 146.0, 136.7, 133.5, 131.9, 130.7, 129.7, 128.9, 127.4, 126.0, 125.5, 125.0, 124.8, 122.1, 119.1, 117.9, 114.6, 114.3, 106.7, 106.3, 101.3, 99.8, 68.0, 67.9, 67.6, 29.9, 29.8, 29.7, 29.6, 29.54, 29.5, 29.32, 29.3, 29.18, 29.15, 28.9, 26.1, 26.0, 20.3; IR (ATR) 2925, 2852, 1603, 1488, 1466, 1381, 1249, 1173, 1151, 1017, 834, 758 cm−1; HR-MS (ESI) Calcd for C79H91O7N2 ([M + H]+): 1179.6821. Found: 1179.6821. ((2-((20-Bromoicosyl)oxy)phenyl)ethynyl)trimethylsilane (S8a, Procedure B). A solution of 20-bromoicosan-1-ol2e (S6, 0.201 g, 0.53 mmol) and diethyl azodicarboxylate (40% toluene solution, 0.36 mL, 0.79 mmol) in dry THF (0.7 mL) was added to a solution of 2((trimethylsilyl)ethynyl)phenol3 (0.15 g, 0.79 mmol) and PPh3 (0.20 g, 0.79 mmol) in dry THF (0.7 mL) and the mixture was refluxed under Ar atmosphere for overnight. After stirring, the solvent was removed in vacuo and CH2Cl2 and H2O were added to the residue. The organic and aqueous layers were separated and the aqueous layer was extracted with CH2Cl2. The combined organic layer was washed with water, dried over Na2SO4, and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel, using hexane−AcOEt (40/1 (v/v) as the eluent) to afford S8a (0.20 g, 0.36 mmol, 67%) as a colorless oil; 1H NMR (300 MHz, CDCl3):δ 7.41 (dd, J = 7.6, 1.7 Hz, 1H), 7.39−7.20 (m, 1H), 6.87−6.80 (m, 2H), 4.36 (t, J = 6.4 Hz, 2H), 3.76 (t, J = 6.9 Hz, 2H), 2.22−2.18 (m, 4H), 1.86−1.27 (m, 32H), 0.26 (s, 9H); 13C NMR (125 MHz, CDCl3):δ 160.2, 133.5, 129.8, 120.1, 112.6, 111.8, 101.4, 98.2, 68.5, 34.0, 32.8, 29.7, 29.66, 29.6, 29.5, 29.4, 29.3, 28.7, 28.1, 26.0, 0.0; IR (ATR) 2917, 2849, 2157, 1593, 1491, 1471, 1443, 1289, 1281, 1257, 1244, 1204, 1158, 1109 cm−1; HR-MS (FAB) Calcd for C31H53OBrSi [M+]: 548.3049. Found 548.3049. ((3-((20-Bromoicosyl)oxy)phenyl)ethynyl)trimethylsilane (S8b). Procedure B was generally followed to synthesize S8b from 3((trimethylsilyl)ethynyl)phenol3 (S7b, 0.39 g, 2.0 mmol). The crude mixture was purified by flash column chromatography (silica gel using, hexane−AcOEt (25/1 (v/v) as the eluent) to afford S8b (0.30 g, 0.54 mmol, 61%) as a white solid; mp 59.6−60.4 °C; 1H NMR (300 MHz, CDCl3):δ 7.14 (t, J = 7.9 Hz, 1H), 7.00 (d, J = 7.7 Hz, 1H), 6.94 (s, 1H), 6.82 (dd, J = 8.3 Hz, 1.1 Hz, 1H), 3.89 (t, J = 6.5 Hz, 2H), 3.37 (t, J = 6.9 Hz, 2H), 1.80−1.73 (m, 4H), 1.40−1.22 (m, 32H), 0.21 (s, 9H); 13C NMR (125 MHz, CDCl3):δ 158.8, 129.2, 124.3, 11 7.2, 115.9, 105.1, 93.8, 68.0, 34.1, 32.8, 29.7, 29.67, 29.6, 29.59, 29.57, 29.5, 29.44, 29.4, 29.2, 28.8, 28.2, 26.0, 0.0; IR (ATR) 3734, 2918, 2850, 2361, 2341, 2154, 1602, 1574, 1467, 1432, 1288, 1250, 1157, 1037, 1027, 842 cm−1; HR-MS (FAB) Calcd for C31H53OBrSi [M+]: 548.3049. Found 548.3048. ((4-((20-Bromoicosyl)oxy)phenyl)ethynyl)trimethylsilane (S8c). Procedure B was generally followed to synthesize S8c from 4((trimethylsilyl)ethynyl)phenol2e (S7c, 0.38 g, 0.79 mmol). The crude mixture was purified by flash column chromatography (silica gel) using hexane−AcOEt (40/1 (v/v)) as the eluent to afford S8c (0.14 g, 0.26 mmol, 52%) as a white solid; mp 66.2−67.0 °C; 1H NMR (300 MHz, CDCl3):δ 7.36 (d, J = 8.9 Hz, 2H), 6.78 (d, J = 8.9 Hz, 2H), 3.92 (t, J = 6.5 Hz, 2H), 3.39 (t, J = 6.9 Hz, 2H), 1.85−1.72 (m, 4H), 1.40−1.24 (m, 32H), 0.21 (s, 9H); 13C NMR (125 MHz, CDCl3):δ 159.4, 133.4, 115.0, 114.3, 105.3, 92.3, 68.1, 34.0, 32.9, 29.68, 29.65, 29.61, 29.58, 29.5, 29.44, 29.4, 29.2, 28.8, 28.2, 26.0, 0.0; IR (ATR) 2919, 2849, 2160, 1604, 1505, 1473, 1464, 1243 cm−1; HR-MS (ESI) Calcd for C31H54OSiBr [(M+H)+]: 549.3122. Found: 549.3128. 2-(4-((20-(2-Ethynylphenoxy)icosyl)oxy)phenyl)-3-iodo-4H-chromen-4-one (8a, Procedure C). A mixture of S5 (0.050 g, 0.14 mmol), S8a (0.078 g, 0.14 mmol), and K2CO3 (0.19 g, 1.4 mmol) in dry DMF (5 mL) was stirred at 60 °C for overnight. The solvent was removed in vacuo, and CH2Cl2 and H2O were added to the residue. The organic and aqueous layers were separated and the aqueous layer was extracted with CH2Cl2. The combined organic layer was washed with water, dried over Na2SO4, and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel, using hexane− AcOEt (10/1 (v/v)) as the eluent) to afford 8a (0.076 g, 0.098 mmol, 70%) as a white solid; mp 71.0−72.6 °C; 1H NMR (300 MHz, CDCl3):δ 8.26 (dd, J = 8.0, 1.4 Hz, 1H), 7.77 (d, J = 8.9 Hz, 2H), 7.68

(ddd, J = 7.2, 6.9, 1.8 Hz, 1H), 7.44 (m, 3H), 7.27 (m, 1H), 6.99 (d, J = 8.9 Hz, 2H), 6.86(m, 2H), 4.02 (m, 4H), 3.23 (s, 1H), 1.86−1.76 (m, 4H), 1.49−1.24 (m, 32H); 13C NMR (125 MHz, CDCl3):δ 174.6, 164.4, 161.3, 160.2, 155.8, 134.04, 134.01, 131.3, 130.1, 126.8, 126.7, 125.7, 120.2, 120.0, 117.5, 114.0, 112.0, 80.9, 80.1, 68.7, 68.3, 29.7, 29.6, 29.57, 29.55, 29.4, 29.3, 29.1, 29.0, 26.0, 25.9; IR (ATR) 3300, 3064, 2914, 2850, 1650, 1609, 1507, 1493, 1468, 1446, 1254, 1185, 1110, 1060, 1023, 755 cm−1; HR-MS (ESI) Calcd for C43H53IO4Na [(M+Na)+]: 783.2881 Found: 783.2895. 2-(4-((20-(3-Ethynylphenoxy)icosyl)oxy)phenyl)-3-iodo-4H-chromen-4-one (8b). Procedure C was generally followed to synthesize 8b from S8b (0.35 g, 0.64 mmol). The crude sample was purified by flash column chromatography (silica gel, using hexane−AcOEt (7/1 (v/v) as the eluent) to afford 8b (0.32 g, 0.17 mmol, 66%) as a white solid; mp 91.2−92.2 °C; 1H NMR (300 MHz, CDCl3):δ 8.26 (dd, J = 8.1, 1.5 Hz, 1H), 7.77 (d, J = 8.9 Hz, 2H), 7.69 (ddd, J = 7.2, 7.2, 1.8 Hz, 1H), 7.47−7.41 (m, 2H), 7.19 (t, J = 7.9 Hz, 1H), 7.04 (d, J = 7.9 Hz, 1H), 7.00−6.99 (m, 3H), 6.87 (dd, J = 8.3, 1.8 Hz, 1H), 4.03 (t, J = 6.5 Hz, 2H), 3.91 (t, J = 6.5 Hz, 2H), 3.02 (s, 1H), 1.83−1.72 (m, 4H), 1.49−1.24 (m, 32H); 13C NMR (125 MHz, CDCl3):δ 174.7, 164.4, 161.3, 158.8, 155.8, 134.0, 131.3, 129.3, 126.9, 126.7, 125.7, 124.4, 123.0, 120.0, 117.57, 117.53, 116.0, 114.0, 87.5, 83.6, 76.8, 68.3, 68.0, 29.7, 29.58, 29.56, 29.3, 29.2, 29.1, 26.0; IR (ATR) 3288, 2914, 2849, 1641, 1610, 1504, 1466, 1254, 1174, 1154, 1061, 1023, 751 cm−1; HRMS (ESI) Calcd for C43H54O4I [(M+H)+]: 761.3061. Found: 761.3065. 2-(4-((20-(4-Ethynylphenoxy)icosyl)oxy)phenyl)-3-iodo-4H-chromen-4-one (8c). Procedure C was generally followed to synthesize 8c from S8c (0.068 g, 0.18 mmol). The crude sample was purified by flash column chromatography (silica gel, using hexane−AcOEt (10/1 (v/v) as the eluent) to afford 8c (0.10 g, 0.14 mmol, 70%) as a white solid; mp 117.0−117.7 °C; 1H NMR (300 MHz, CDCl3):δ 8.26 (dd, J = 8.1, 1.5 Hz, 1H), 7.78 (d, J = 4.5 Hz, 2H), 7.69 (ddd, J = 7.2, 7.2, 1.8 Hz, 1H), 7.48−7.37 (m, 4H), 7.39 (d, J = 4.3 Hz, 2H), 6.99 (d, J = 8.6, 4.3 Hz, 2H), 6.80 (d, J = 8.6 Hz, 2H), 4.03 (t, J = 6.5 Hz, 2H), 3.93 (t, J = 6.5 Hz, 2H), 2.96 (s, 1H), 1.83−1.73 (m, 4H), 1.47−1.24 (m, 32H); 13C NMR (125 MHz, CDCl3):δ 174.6, 164.3, 161.3, 159.5, 155.8, 134.0, 133.5, 131.3, 126.8, 126.7, 125.7, 119.9, 117.5, 114.4, 114.0, 113.8, 87.5, 83.7, 75.6, 68.2, 68.0, 29.7, 29.6, 29.55, 29.5, 29.3, 29.1, 25.99, 25.97; IR (ATR) 3286, 2916, 2848, 1606, 1504, 1462, 1249, 1175, 1026, 833 cm−1; HR-MS (ESI) Calcd for C43H54O4I [(M +H)+]: 761.3061. Found: 761.3061. [2]Catenane (9Aa). Procedure A was generally followed to synthesize 9Aa from 8a (0.020 g, 0.025 mmol). The crude sample was purified by column chromatography (silica gel, using CH2Cl2 as the eluent) and GPC to afford 9Aa (5.0 mg, 0.0039 mmol, 16%) as a yellow amorphous solid; 1H NMR (500 MHz, CDCl3):δ 8.34 (d, J = 9.2 Hz, 4H), 8.29 (d, J = 8.6 Hz, 2H), 8.20 (dd, J = 7.7, 1.4 Hz, 1H), 8.17 (d, J = 8.6 Hz, 2H), 7.98 (dd, J = 8.6, 4.3 Hz, 2H), 7.67 (s, 2H), 7.55 (dd, J = 7.4, 1.7 Hz, 1H), 7.51 (ddd, J = 7.5, 7.5, 1.5 Hz, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.31 (t, J = 7.4 Hz, 1H), 7.24−7.20 (m, 3H), 7.02 (t, J = 8.0 Hz, 1H), 6.94 (d, J = 9.2, 4H), 6.87 (t, J = 4.0 Hz, 2H), 6.46 (s, 1H), 6.37 (dd, J = 8.0, 2.3 Hz, 2H), 3.94 (t, J = 7.4 Hz, 2H), 3.89− 3.81 (m, 10H), 1.79−1.11 (m, 52H); 13C NMR (125 MHz, CDCl3):δ 176.7, 164.5, 161.6, 160.3, 159.6, 156.1, 155.2, 145.9, 136.6, 131.8, 130.7, 129.7, 128.8, 127.4, 126.1, 125.5, 124.3, 122.2, 120.1, 119.1, 114.5, 114.2, 113.0, 112.1, 106.7, 105.9, 101.1, 95.3, 85.6, 68.7, 67.9, 67.8, 67.6, 29.7, 29.6, 29.3, 29.2, 29.1, 28.9, 28.8, 26.0, 25.9, 25.8, 25.5; IR (ATR) 2922, 2851, 2359, 2342, 1602, 1488, 1466, 1377, 1304, 1249, 1173. 1151, 1018, 830 cm−1; HR-MS (ESI) Calcd for C85H95O8N2 [(M+H)+]: 1271.7082. Found: 1271.7070. [2]Catenane (9Ab). Procedure A was generally followed to synthesize 9Ab from 8b (0.037 g, 0.049 mmol). The crude sample was purified by column chromatography (silica gel, using CH2Cl2 as the eluent), GPC and PTLC using CH2Cl2 as the eluent to afford 9Ab (8.0 mg, 0.0063 mmol, 30%) as a yellow amorphous solid; 1H NMR (500 MHz, CDCl3):δ 8.37 (d, J = 4.6 Hz, 5H), 8.25−8.20 (m, 5H), 8.00 (d, J = 8.0 Hz, 2H), 7.68 (s, 2H), 7.55 (ddd, J = 7.0, 7.0, 1.5 Hz, 1H), 7.44 (d, J = 8.6 Hz, 1H), 7.36 (t, J = 7.5 Hz, 1H), 7.22−7.20 (m, 2H), 7.12 (s, 1H), 7.08 (t, J = 8.3 Hz, 1H), 6.95 (d, J = 8.6 Hz, 4H), 6122

DOI: 10.1021/acs.joc.7b00672 J. Org. Chem. 2017, 82, 6118−6124

Article

The Journal of Organic Chemistry 6.91 (d, J = 9.2 Hz, 2H), 6.82 (d, J = 8.0 Hz, 1H), 6.60 (s, 1H), 6.43 (dd, J = 8.0, 2.3 Hz, 2H), 3.94−3.89 (m, 10H), 3.77 (t, J = 6.3 Hz, 2H), 3.68 (t, J = 6.6 Hz, 2H), 1.80−1.75 (m, 10H), 1.59−1.07 (m, 42H).; 13C NMR (125 MHz, CDCl3):δ 176.6, 161.9, 160.4, 160.3, 156.2, 155.2, 146.0, 136.6, 133.6, 131.9, 130.6, 129.7, 129.4, 128.9, 127.4, 126.0, 125.5, 125.3, 124.7, 124.3, 122.1, 119.1, 117.9, 116.9, 115.2, 114.6, 114. 3, 106.9, 101.3, 98.4, 82.1, 68.1, 68.0, 67.7, 29.7, 29.4, 29.39, 29.37, 29.35, 29.31, 29.27, 29.23, 29.17, 29.14, 29.10, 26.0, 25.9, 25.7; IR (ATR) 2932, 2851, 1647, 1601, 1488, 1466, 1377, 1249, 1173, 1017, 835 cm−1; HR-MS (ESI) Calcd for C85H95O8N2 [(M +H)+]: 1271.7082. Found: 1271.7066. The yield of 9Ab increased to 50% (0.011 g, 0.0087 mmol) when procedure D (vide infra) was generally followed to synthesize 9Ab from 1A-CuI (0.015 g, 0.018 mmol). [2]Catenane (9Ac). Procedure A was generally followed to synthesize 9Ac from 8c (0.081 g, 0.10 mmol). The crude sample was purified by column chromatography (silica gel, using CH2Cl2 as the eluent) to afford 9Ac (8.0 mg, 0.0063 mmol, 13%) as a yellow amorphous solid; 1H NMR (500 MHz, CDCl3):δ 8.37 (d, J = 8.6 Hz, 4H), 8.23 (d, J = 9.5 Hz, 2H), 8.19 (d, J = 9.0 Hz, 2H), 7.99 (d, J = 8.6 Hz, 2H), 7.68 (s, 2H), 7.56 (ddd, J = 7.0, 7.0, 2.0 Hz, 1H), 7.45 (d, J = 8.5 Hz, 1H), 7.42 (d, J = 8.5 Hz, 2H), 7.36 (t, J = 8.0 Hz, 1H), 7.10 (t, J = 8.0 Hz, 1H), 6.99−6.96 (m, 6H), 6.74 (d, J = 8.6 Hz, 2H), 6.53 (s, 1H), 6.45 (dd, J = 8.0, 2.3 Hz, 2H), 3.93−3.90 (m, 10H), 3.83 (t, J = 6.6 Hz, 2H), 1.85−1.23 (m, 52H); 13C NMR (125 MHz, CDCl3):δ 176.6, 165.2, 161.8, 160.4, 160.3, 159.2, 156.2, 155.3, 146.0, 136.6, 133.6, 133.0, 132.0, 130.9, 129.8, 128.9, 127.4, 126.1, 125.5, 125.2, 124.5, 122.2, 119.2, 117.9, 114.6, 114.5, 114.1, 106.7, 101.4, 97.6, 81.0, 68.2, 68.0, 67.7, 67.6, 29.7, 29.6, 29.53, 29.5, 29.45, 29.42, 29.4, 29.3, 29.24, 29.21, 29.0, 28.8, 26.1, 26.0, 25.9, 25.8; IR (ATR) 3734, 2923, 2851, 2360, 2341, 1654, 1603, 1488, 1466, 1386, 1247, 1185, 1168, 1105, 1018, 832 cm−1; HR-MS (ESI) Calcd for C85H95O8N2 [(M +H)+]: 1271.7083. Found: 1271.7074. [2]Catenane (9Bb, Procedure D). A mixture of macrocyclic phenanthroline-CuI complex 1B-CuI3 (0.017 g, 0.019 mmol), 8b (0.063 g, 0.096 mmol), and K2CO3 (0.023 g, 0.17 mmol) in dry xylene ([1B-CuI] = 1.8 mM, 11 mL) was stirred at 120 °C for 48 h. The mixture was cooled to room temperature and CH2Cl2, CH3CN, and NH3 aq. (30% solution, 5.0 mL) were added. After stirring at room temperature for overnight, the mixture was extracted with CH2Cl2. The organic layer was dried over Na2SO4 and concentrated in vacuo. The crude product was purified by column chromatography (silica gel, using CH2Cl2 as the eluent) and GPC to afford 9Bb (0.016 g, 0.012 mmol, 64%) as a yellow amorphous solid; 1H NMR (500 MHz, CDCl3):δ 8.38 (dd, J = 4.3, 2.1 Hz, 3H), 8.24−8.18 (m, 4H), 8.00 (d, J = 4.9 Hz, 2H), 7.67 (s, 2H), 7.55 (t, J = 7.7 Hz, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.33 (t, J = 7.4 Hz, 1H), 7.22−7.20 (m, 2H), 7.07 (m, 2H), 6.97 (d, J = 7.5 Hz, 4H), 6.90 (d, J = 8.0 Hz, 2H), 6.82 (dd, J = 8.0, 1.1 Hz, 1H), 6.46 (s, 1H), 6.42 (dd, J = 8.0, 2.3 Hz, 2H), 3.92 (t, J = 6.6 Hz, 4H), 3.87 (t, J = 6.0 Hz, 4H), 3.80 (t, J = 6.0 Hz, 2H), 3.75 (t, J = 6.3 Hz, 2H), 1.78−1.72 (m, 8H), 1.61−1.50 (m, 52H); 13C NMR (125 MHz, CDCl3):δ 176.7, 165.0, 161.9, 160.4, 160.3, 158.9, 156.1, 155.2, 146.0, 136.6, 133.6, 131.7, 130.6, 129.7, 129.3, 128.9, 127.4, 126.0, 125.5, 125.2, 124.7, 124.3, 124.2, 122.0, 119.0, 117.9, 117.1, 114.8, 114.6, 114.2, 106.8, 105.4, 100.9, 98.3, 82.0, 68.1, 68.0, 67.9, 67.7, 29.4, 29.34, 29.3, 29.26, 29.22, 29.2, 29.17, 29.1, 29.0, 26.9, 25.9, 25.8, 25.7; IR (ATR): 2923, 2852, 1648, 1601, 1574, 1488, 1466, 1375, 1250, 1206, 1173, 1150, 1112, 1021, 835 cm−1; HR-MS (ESI) Calcd for C89H103N2O8 [(M+H)+]: 1327.7709. Found: 1327.7698. [2]Catenane (9Cb). Procedure D was generally followed to synthesize 9Cb from 1C-CuI3 (0.014 g, 0.015 mmol) and 8b (0.051 g, 0.078 mmol). The crude sample was purified by column chromatography (silica gel, using CH2Cl2 as the eluent) and GPC to afford 9Cb (5.0 mg, 0.0036 mmol, 24%) as a yellow amorphous solid; 1H NMR (500 MHz, CDCl3):δ 8.37 (d, J = 8.6 Hz, 4H), 8.28− 8.16 (m, 5H), 8.01 (d, J = 8.6 Hz, 2H), 7.68 (s, 2H), 7.57 (ddd, J = 7.5, 7.5, 1.5 Hz, 1H), 7.40 (d, J = 8.0 Hz, 1H), 7.35 (t, J = 7.4 Hz, 1H), 7.23−7.21 (m, 3H), 7.09−7.08 (m, 2H), 6.99 (d, J = 8.5 Hz, 4H), 6.91 (d, J = 9.0 Hz, 2H), 6.82 (dd, J = 8.0, 1.7 Hz, 1H), 6.45 (s, 1H), 6.42 (dd, J = 8.6, 2.3 Hz, 2H), 3.92 (t, J = 7.7 Hz, 4H), 3.87 (t, J = 6.3 Hz,

4H), 3.80 (t, J = 6.3 Hz, 2H), 3.75 (t, J = 6.9 Hz, 2H), 1.75−1.71 (m, 10H), 1.34−1.25 (m, 58H); 13C NMR (125 MHz, CDCl3):δ 176.7, 165.0, 161.9, 160.4, 160.3, 159.0, 156.2, 155.2, 146.0, 136.6, 131.7, 130.6, 128.9, 127.4, 125.4, 124.3, 124.2, 122.1, 119.2, 119.1, 119.06, 114.9, 114.62, 114.60, 114.3, 106.7, 106.6, 105.4, 101.14, 101.10, 98.4, 81.9, 68.05, 68.02, 67.9, 67.7, 29.5, 29.4, 29.38, 29.3, 29.2, 29.1, 26.1, 26.0, 25.9, 25.8, 25.7 (some signals are missing); IR (ATR) 2923, 2851, 2363, 2337, 1601, 1488, 1465, 1378, 1244, 1173, 1149, 1018, 834 cm−1; HR-MS (ESI) Calcd for C93H111N2O8 [(M+H)+]: 1383.8335. Found: 1383.8336. ((3-((15-Bromopentadecyl)oxy)phenyl)ethynyl)trimethylsilane (S10a, Procedure E). A mixture of S7b (0.105g, 0.55 mmol) and PPh3 (0.14 g, 0.55 mmol) in dry THF (0.8 mL) was added to a solution of 15-bromo-1-pentadecanol2e (S9a, 0.11 g, 0.36 mmol) and diethyl azodicarboxylate (40% toluene solution, 0.25 mL, 0.55 mmol) in dry THF (0.8 mL), and the solution was refluxed under Ar atmosphere for overnight. The solvent was removed in vacuo and CH2Cl2 and H2O were added to the residue. The organic and aqueous layers were separated and the aqueous layer was extracted with CH2Cl2. The combined organic layer was washed with water, dried over Na2SO4, and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel, using hexane−AcOEt (40/1 (v/v)) as the eluent) to afford S10a (0.13 g, 0.28 mmol, 76%) as a colorless oil; 1H NMR (300 MHz, CDCl3):δ 7.16 (t, J = 7.9 Hz, 1H), 7.02 (d, J = 8.6 Hz, 1H), 6.96 (s, 1H), 6.84 (dd, J = 8.3, 1.1 Hz, 1H), 3.91 (t, J = 6.5 Hz, 2H), 3.39 (t, J = 6.9 Hz, 2H), 1.82−1.75 (m, 4H), 1.42−1.25 (m, 22H), 0.23 (s, 9H); 13C NMR (125 MHz, CDCl3):δ 158.8, 129.2, 124.3, 124.0, 115.8, 105.1, 93.7, 68.0, 34.0, 32.8, 29.62, 29.6, 29.57, 29.55, 29.53, 29.4, 29.3, 29.2, 28.8, 28.2, 26.0, 0.0; IR (ATR) 2923, 2852, 2155, 1574, 1468, 1284, 1249, 1159, 840 cm−1; HR-MS (FAB) Calcd for C26H43OBrSi [M+]: 478.2267. Found 478.2263. ((3-((12-Bromododecyl)oxy)phenyl)ethynyl)trimethylsilane (S10b). Procedure E was generally followed to synthesize S10b from 12-bromo-1-dodecanol (S9b, 1.0 g, 3.7 mmol). The crude product was purified by flash column chromatography (silica gel, using hexane− AcOEt (20/1 (v/v)) as the eluent) to afford S10b (0.97 g, 2.2 mmol, 60%) as a colorless oil; 1H NMR (300 MHz, CDCl3):δ 7.16 (t, J = 7.9 Hz, 1H), 7.02 (dd, J = 7.6, 1.2 Hz, 1H), 6.96 (s, 1H), 6.84 (dd, J = 8.1, 0.9 Hz, 1H), 3.91 (t, J = 6.5 Hz, 2H), 3.39 (t, J = 6.9 Hz, 2H), 1.88− 1.72 (m, 4H), 1.70−1.27 (m, 16H), 0.23 (s, 9H); 13C NMR (125 MHz, CDCl3):δ 158.7, 129.2, 124.3, 123.9, 117.1, 115.8, 105.1, 93.7, 68.0, 34.0, 32.8, 29.5, 29.47, 29.4, 29.3, 29.2, 28.7, 28.1, 26.0, −0.1; IR (ATR) 2924, 2853, 2155, 1574, 1468, 1284, 1249, 1155, 840 cm−1; Anal. Calcd for C23H37OBrSi; C, 63.14 H, 8.52. Found C, 63.14; H, 8.71. 2-(4-((15-(3-Ethynylphenoxy)pentadecyl)oxy)phenyl)-3-iodo-4Hchromen-4-one (8d, Procedure F). A mixture of S6 (0.10 g, 0.28 mmol), S10a (0.13 g, 0.28 mmol), and K2CO3 (0.39 g, 2.8 mmol) in dry DMF (5 mL) was stirred at 60 °C for overnight. After stirring, the solvent was removed in vacuo, and CH2Cl2 and H2O were added to the residue. The organic and aqueous layers were separated and the aqueous layer was extracted with CH2Cl2. The combined organic layer was washed with water, dried over Na2SO4, and concentrated in vacuo. The residue was purified by flash column chromatography (silica gel, using hexane−AcOEt (10/1 (v/v) as the eluent) to afford 8d (0.16 g, 0.24 mmol, 84%) as a white solid; mp 75.8−76.9 °C; 1H NMR (300 MHz, CDCl3):δ 8.25 (dd, J = 8.1, 1.5 Hz, 1H), 7.77 (d, J = 9.4 Hz, 2H), 7.68 (ddd, J = 7.2, 7.2, 1.5 Hz, 1H), 7.48−7.39 (m, 2H), 7.19 (t, J = 7.9 Hz, 1H), 7.04 (dd, J = 6.5, 5.5 Hz, 1H), 7.02−6.97 (m, 3H), 6.87 (dd, J = 8.4, 1.3 Hz, 1H), 4.02 (t, J = 6.5 Hz, 2H), 3.91 (t, J = 6.5 Hz, 2H), 3.03 (s, 1H), 1.81−1.72 (m, 4H), 1.46−1.26 (m, 22H); 13C NMR (125 MHz, CDCl3):δ 174.6, 164.4, 161.3, 158.8, 155.8, 155.7, 134.0, 131.3, 129.3, 126.8, 126.7, 125.7, 124.4, 122.9, 119.9, 117.5, 115.9, 114.0, 87.5, 83.6, 76.8, 68.2, 68.0, 29.62, 29.6, 29.5, 29.3, 29.1, 26.0, 25.9; IR (ATR) 3295, 2914, 2851, 1740, 1645, 1608, 1505, 1468, 1329, 1253, 1184, 1059, 757 cm−1; HR-MS (ESI) Calcd for C38H43IO4Na [(M+Na)+]: 713.2098. Found: 713.2129. 2-(4-((12-(3-Ethynylphenoxy)dodecyl)oxy)phenyl)-3-iodo-4Hchromen-4-one (8e). Procedure F was generally followed to synthesize 8e from S10b (0.54 g, 0.15 mmol). The crude sample 6123

DOI: 10.1021/acs.joc.7b00672 J. Org. Chem. 2017, 82, 6118−6124

The Journal of Organic Chemistry

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was purified by flash column chromatography (silica gel, using hexane−AcOEt (10/1 (v/v) as the eluent) to afford 8e (0.080 g, 0.12 mmol, 84%) as a yellow solid; mp 81.5−82.4 °C; 1H NMR (300 MHz, CDCl3):δ 8.26 (dd, J = 8.0, 1.4 Hz, 1H), 7.77 (d, J = 8.9 Hz, 2H), 7.68 (ddd, J = 7.2, 6.9, 1.5 Hz, 1H), 7.48−7.40 (m, 2H), 7.19 (t, J = 7.9 Hz, 1H), 7.21−6.99 (m, 4H), 6.87 (dd, J = 8.4, 1.8 Hz, 1H), 4.03 (t, J = 6.5 Hz, 2H), 3.92 (t, J = 6.5 Hz, 2H), 3.02 (s, 1H), 1.84−1.73 (m, 4H), 1.46−1.29 (m, 16H); 13C NMR (125 MHz, CDCl3):δ 174.6, 164.4, 161.3, 158.8, 155.8, 134.0, 131.3, 129.3, 126.9, 126.7, 125.7, 124.4, 123.0, 112.0, 117.6, 117.5, 115.9, 114.0, 87.5, 83.6, 76.8, 68.2, 68.0, 29.5, 29.4, 29.16, 29.14, 26.0; IR (ATR) 3300, 2921, 2850, 2361, 2342, 1637, 1604, 1572, 1501, 1466, 1288, 1258 cm−1; HR-MS (ESI) Calcd for C35H37IO4Na [(M+Na)+]: 671.1629. Found: 671.1642. [2]Catenane 10. Procedure D was generally followed to synthesize 10 from 1A-CuI2 (0.016 g, 0.019 mmol) and 8d (0.063 g, 0.098 mmol). The crude sample was purified by column chromatography (silica gel, using CH2Cl2 as the eluent) and GPC to afford 10 (0.011 g, 0.0092 mmol, 48%) as a yellow amorphous solid; 1H NMR (500 MHz, CDCl3):δ 8.41 (d, J = 8.6 Hz, 4H), 8.24−8.21 (m, 3H), 8.14 (d, J = 9.2 Hz, 2H), 8.05 (d, J = 8.6 Hz, 2H), 7.72 (s, 2H), 7.56 (ddd, J = 7.5, 7.5, 1.5 Hz, 1H), 7.45 (d, J = 8.0 Hz, 1H), 7.35 (t, J = 7.2 Hz, 1H), 7.31−7.28 (m, 3H), 7.05−7.01 (m, 2H), 6.97−6.92 (m, 6H), 6.86 (ddd, J = 7.5, 2.0, 2.0 Hz, 1H), 6.47 (s, 1H), 6.37 (dd, J = 8.6, 2.5 Hz, 2H), 3.95 (t, J = 6.3 Hz, 2H), 3.87−3.83 (m, 10H), 1.79−1.23 (m, 32H); 13C NMR (125 MHz, CDCl3):δ 176.7, 165.6, 161.7, 160.4, 160.2, 158.8, 156.2, 155.3, 146.0, 136.7, 133.6, 131.9, 130.7, 129.6, 129.4, 128.8, 127.4, 126.1, 125.5, 125.3, 124.9, 124.6, 124.2, 122.2, 119.1, 118.7, 118.0, 114.6, 114.4, 113.7, 106.8, 105.9, 101.2, 97.3, 81.7, 68.0, 67.6, 67.5, 67.4, 29.9, 29.7, 29.6, 29.4, 29.37, 29.32, 29.3, 29.26, 29.2, 29.09, 29.05, 26.2, 26.1, 25.8; IR (ATR) 2924, 2852, 1649, 1603, 1587, 1573, 1509, 1488, 1466, 1380, 1250, 1173, 1152, 1021, 835 cm−1; HR-MS (ESI) Calcd for C80H85N2O8 [(M+H)+]: 1201.6300. Found: 1201.6290. Macrocycle (12). Compound 12 (0.005 g, 0.008 mmol, ca. 20% yield based on 8b) was isolated when the synthesis of [2]catenane 9Ab from 8b (0.037 g, 0.048 mmol) was examined. Column chromatography (silica gel, using CH2Cl2 as the eluent) afforded the macrocycle 12 as a white solid; mp 144.0−145.1 °C; 1H NMR (500 MHz, CDCl3):δ 8.27−8.25 (m, 3H), 7.68 (ddd, J = 7.0, 7.0, 2.0 Hz, 1H), 7.51 (d, J = 9.0 Hz, 1H), 7.41 (t, J = 8.0 Hz, 1H), 7.23−7.19 (m, 3H), 7.04−7.01 (m, 2H), 6.95 (s, 1H), 6.86 (ddd, J = 8.0, 1.5, 1.5 Hz, 1H), 4.04 (t, J = 6.3 Hz, 2H), 3.93 (t, J = 6.3 Hz, 2H), 1.82−1.23 (m, 36H); 13 C NMR (125 MHz, CDCl3):δ 176.7, 165.4, 161.9, 158.8, 155.4, 133.8, 130.8, 129.4, 126.2, 125.4, 124.48, 124.45, 124.3, 122.2, 117.9, 117.1, 115.0, 114.2, 105.8, 97.8, 82.1, 68.3, 68.1, 29.17, 29.15, 29.12, 29.08, 29.05, 28.9, 28.8, 28.78, 28.73, 28.66, 28.6, 25.91, 25.9; IR (ATR) 2922, 2850, 2360, 2341, 1645, 1603, 1573, 1508, 1461, 1387, 1254, 1207, 1177, 763 cm−1; HR-MS (ESI) Calcd for C43H53O4 [(M +H)+]: 633.3938. Found 633.3941.

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ACKNOWLEDGMENTS This work was supported in part by JSPS KAKENHI Grant Number 26410125. REFERENCES

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The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b00672. Comparison of the 1H NMR spectra of 7 and related compounds, and NMR spectra (1H, 13C) for new compounds (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Yuichiro Mutoh: 0000-0002-5254-9383 Shinichi Saito: 0000-0001-8520-1116 Notes

The authors declare no competing financial interest. 6124

DOI: 10.1021/acs.joc.7b00672 J. Org. Chem. 2017, 82, 6118−6124