Fluorescence Turn-on Enantioselective Recognition of both Chiral

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The Journal of Organic Chemistry

Fluorescence Turn-on Enantioselective Recognition of Both Chiral Acidic Compounds and α-Amino Acids by Chiral Tetraphenylethylene Macrocycle Amine Hai-Tao Feng, Xing Zhang, and Yan-Song Zheng* Key Laboratory for Large-Format Battery Materials and System, Ministry of Education, School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology, Wuhan, China E-mail: [email protected] TABLE OF CONTENTS

ABSTRACT: New chiral tetraphenylethylene (TPE) macrocycles bearing optical pure amine groups were synthesized and found to have a discriminating ability between the two enantiomers of not only chiral acidic compounds but also α-amino acids by enantioselective aggregation and aggregation-induced emission (AIE) effect. NMR spectra including 2D-NOESY disclosed that the host-guest interaction of the macrocycle receptor played a key role in addition to the acid-base interactions. INTRODUCTION Chiral recognition is an important process in natural world, which plays a vital role in asymmetric synthesis, chiral drugs separation, organic three-dimensional structure theory, and the chiral origin of life. However, how to distinguish the two chiral enantiomers is still a challenge. The various techniques that have been applied to the discrimination and analysis of enantiomers

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include high performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR), UV/Vis, circular dichroism (CD) and fluorescence spectroscopy.1 Among them, chiral recognition through fluorescence change attracts keen interest because it can provide time-efficient, accurate, and sensitive enantiomer determination of chiral compounds.2-3 The enantioselective recognition of chiral amines, acids or modified amino acids has been actively investigated by fluorescence spectroscopy,4 because of the importance of this class of compounds in biological processes as well as in organic synthesis. However, the selective detection of unprotected α-amino acids by fluorescence strategy is still a challenging assignment due to the zwitterion property of the α-amino acids which results in very little solubility of them in organic solvents and little interaction with organic fluorophores in water.5 Rare examples for chiral detection of α-amino acids by a fluorescent probe have been reported.6 Recently, a new class of aggregation-induced emission (AIE) compounds, which are non-emissive in solution but emit strong fluorescence upon aggregation, attracts intensive attention because of their great potential for applications as optoelectronic materials and fluorescence sensors.7 In 2009， Pu and Hou reported enantioselective precipitation and solid-state fluorescence enhancement when α-hydroxycarboxylic acids were mixed with 1,1’-bi-2-naphtholamine receptor although the receptor was not AIE molecule.5c In 2014, Tang and Wong reported a chiral AIE molecule containing the luminogenic unit silole with chiral recognition of acids by a mechanism of complexation-induced circularly polarised luminescence (CPL) in the solid thin film state.8 Previously, some chiral AIE carboxylic acids or amines were demonstrated to have exceptionally high enantioselectivity and sensitivity for some chiral amines or acids in our group.9 To make the chiral AIE receptors applicable to wider chiral analytes, chiral macrocycle receptors based on AIE


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effect were synthesized,10 with a hope that the additional cavity of the macrocycle could also play the role on interaction with the analytes. Here, we reported that AIE macrocycles bearing optical pure diphenyldiaminoethylene group were synthesized and displayed enantiomer discrimination not only for chiral acidic compounds but also for unprotected α-amino acids. RESULTS AND DISCUSSION Underwent a formylation of the starting material dimethoxyltetraphenylethylene 19b with urotropine in trifluoroacetic acid (TFA), the key intermediate TPE dialdehyde 2 was prepared. A reduction of 2 with NaBH4 that gave the TPE dialcohol 3 followed a chlorinating by thionyl chloride afforded TPE dichloride 410b in 85% yields. Finally, the reaction of (1S, 2S) - or (1R, 2R)-1, 2-diphenyl-1, 2-diaminoethane with TPE dichloride 4 gave the chiral TPE macrocycles (1S, 2S)-5 and (1R, 2R)-6. The macrocycles were characterized by NMR spectra, MS, IR, and optical rotation. Scheme 1. Synthesis of chiral TPE macrocycle (1S, 2S)-5 and (1R, 2R)-6.

As expected, the dilute solution of (1S, 2S)-5 or (1R, 2R)-6 in CHCl3 or THF had almost no fluorescence. But when the non-solvent water was gradually added into the solution of the



macrocycles in THF until a turbid appeared, the resultant suspension started to emit fluorescence. After that, with the rising of water fraction in THF, the fluorescence intensity of the macrocycles increased (Fig. 1). At a ratio of 95:5 H2O/THF (volume ratio, the same below), the fluorescence intensity of the resultant suspension was 400 times larger than that of the solution without water. Therefore, (1S, 2S)-5 and (1R, 2R)-6 are AIE compounds. The fluorescence quantum yield of the suspension of (1S, 2S)-5 and (1R, 2R)-6 in 95% water was 8.7 and 8.1%, respectively, using quinine sulfate as a reference standard. The molar absorptivities of (1S, 2S)-5 and (1R, 2R)-6 in 95% water was 5.06×104 and 5.01×104 L/mol‧cm, respectively.

A 400 300 250 1

200

A a

150

B

100% THF THF:H2O=95:5 THF:H2O=90:10 THF:H2O=80:20 THF:H2O=75:25 THF:H2O=70:30 THF:H2O=60:40 THF:H2O=50:50 THF:H2O=40:60 THF:H2O=30:70 THF:H2O=20:80 THF:H2O=10:90 THF:H2O=5:95

0

200 150 100

100 50

THF100% THF:H2O=90:10 THF:H2O=80:20 THF:H2O=70:30 THF:H2O=60:40 THF:H2O=50:50 THF:H2O=40:60 THF:H2O=35:65 THF:H2O=30:70 THF:H2O=25:75 THF:H2O=20:80 THF:H2O=10:90 THF:H2O=5:95

300 250

Intensity

350

Intensity

50

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400 450 500 550 600 650 700 Wavelength (nm)

0 400

450

500

550

600

650

Wavelength(nm)

Fig. 1. (A) Changes in the fluorescence spectra of (1S,2S)-5 (2.0 × 10-3 M) with increasing water in THF; (B) Changes in the fluorescence spectra of (1R, 2R)-6 (2.0 × 10-3 M) with increasing water in THF. λex = 365 nm, ex/em slits = 5/5 nm. A 250

5+D-Camphor Sulfonic acid 5+L-Camphor Sulfonic acid 5

150 100

5+L-Histidine 5+D-Histidine 5

80 60 40 20

50 0

B

Intensity

200 Intensity

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400

450 500 550 Wavelength(nm)

600

650

0 400

450 500 550 600 Wavelength(nm)

650

Fig. 2. (A) Fluorescence spectra of a mixture of (1S, 2S)-5 and enantiomers of camphor sulfonic


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acid 8 in 1.4:3.3 THF/H2O. [(1S, 2S)-5] = [8] = 4.4×10-4 M. (B) Fluorescence spectra of a mixture of (1S, 2S)-5 and enantiomers of histidine 18 in 11.1:14 THF/H2O. [(1S, 2S)-5] = [18] = 7.9×10-4 M. λex=365 nm, ex/em slits = 5/10 nm. As shown in Fig. 2, Fig. S15–S27 (ESI) and Table 1, the selectivity and chiral recognition ability of (1S, 2S)-5 was tested for a number of chiral acids and amino acids. Aggregates formed enantioselectively when (1S, 2S)-5 and chiral acids or amino acids were mixed in the appropriate solvent. When a mixture of (1S, 2S)-5 and mandelic acid (1:1 molar ratio, 0.5 mM) was dissolved in 7:13.5 THF/ H2O by heating for several minutes. The mixture of (1S, 2S)-5 and R-mandelic acid produced suspended precipitates, but with S-mandelic acid it gave a clear solution under the same condition. The suspended precipitates strongly emitted fluorescence while the solution did not. The maximal fluorescence enhancement ratio IRmax/I0 reached 28.6 and the fluorescence intensity ratio resulted from two enantiomers of 7 was 8.4 (in Table 1). Even for a strong acid, camphor sulfonic acid 8, (1S, 2S)-5 could also discriminate its two enantiomers with a good enantioselectivity of 14.6 and IRmax/I0 of 26.5. Other carboxylic acids, such as N-Boc-methionine 9, Ibuprofen 10 gave a high fluorescence intensity ratio ILmax/I0 of 16.7 and 11.9, respectively. In addition, chiral (1S, 2S)-5 could also discriminate the enantiomers of some α-amino acids. For example, after D or L-histidine was added to (1S, 2S)-5 in a mixed solvent of THF and water, only the mixture of (1S, 2S)-5 and L-histidine appeared precipitates and emitted strong fluorescence but the interaction of (1S, 2S)-5 with D-histidine gave a solution which almost emit no fluorescence (Fig. 2B). The maximal fluorescence enhancement ratio IL/I0 reached 14.2 and the selectivity IL/ID was up to 5.8. For other α-amino acids, including glutamic acid, tyrosine, methionine, phenylalanine, proline, arginine, pyroglutamic acid, and tryptophan, their enantiomers could also



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be discriminated by the chiral TPE macrocycle (1S, 2S)-5 with a good enantioselectivity. Table 1 The enantioselectivity (I1/I2) of (1S, 2S)-5 resulted from two enantiomers of chiral acids I1/I0a

I1/I2b

State

7. Mandelic acid

28.6

8.4

Pre/Sol

8. Camphor sulfonic acid

26.5

14.6

Pre/Sol

9. N-Boc-methionine

16.7

4.2

Pre/Sol

10. Ibuprofen

11.9

2.6

Pre/Sol

11. Glutamic acid

18.2

1.7

Pre/Sol

12. Tyrosine

15.1

2.3

Pre/Sol

13. Methionine

13.5

2.1

Pre/Sol

16.8

2.1

Pre/Sol

15.Proline

11.4

2.2

Pre/Sol

16. Arginine

23.1

1.8

Pre/Sol

17. Pyroglutamic acid

10.2

2.4

Pre/Sol

18. Histidine

14.2

5.8

Pre/Sol

19. Tryptophan

18.9

2.1

Pre/Sol

Entry

Acids

O

14. Phenylalanine

OH NH2

a

I0 is the intensity of (1S, 2S)-5 with no acids; bI1/I2 = Enantiomer 1/ Enantiomer 2, Pre= Precipitates; Sol= Solution.

Due to inherent chiral recognition, using the mirror receptor (1R, 2R)-6 instead of (1S, 2S)-5, a contrary result was obtained in the tests of enantioselective aggregation with the enantiomers of acids or amino acids. So that, by making use of (1S, 2S)-5 and (1R, 2R)-6, the enantiomer composition of the chiral carboxylic acids could be quantitatively measured (Fig. 3). This is very


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important for high throughput analysis of enantiomer purity of chiral drugs and reagents.

(1S,2S)-5+R/S-mandelic acid (1R,2R)-6+R/S-mandelic acid

500 Intensity

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


400

500 A

B

400

300

300

200

200

100

100

0 S100% 0

20 40 60 R-mandelic acid %

80

0 100 R100%

Fig. 3. Change of fluorescence intensity of (1S, 2S)-5 or (1R, 2R)-6 with enantiomer content of 7 in 7:13.5 THF/H2O. [(1S, 2S)-5] = [(1R, 2R)-6] = [7] = 5.0×10-4 M. To have a clear insight into the chiral discrimination ability of (1S, 2S)-5, 1H-NMR titration, and 2D NOESY spectra of mixtures of (1S, 2S)-5 with the enantiomers of R/S-7 were measured. 1H NMR titration of (1S, 2S)-5 with R-7 or S-7 was carried in d-chloroform (Fig. 4, 5 and Fig. S28). When 3 mM (1S, 2S)-5 in CDCl3 was mixed with one molar equivalent of R-7, it could be found that the methoxyphenyl proton (He), phenyl protons (Hd) of (1S, 2S)-5 and proton Hc of R-7 exhibited a downfield shift of 0.0326, 0.0477 and 0.0266 ppm, respectively, while proton Ha of R-7 had a upfield shift of 0.0554 ppm (Fig. 4). Proton Ha and Hd in the mixture of (1S, 2S)-5 with S-7 behaved a same shift direction to that observed with R-7, but the value was less. Proton Ha had an upfield shift (0.0451 ppm) and Hd showed a downfield shift (0.0441 ppm) while other protons had almost no chemical shift change. Due to the 0.01 ppm larger upfield shift of phenyl ring of R-7, it should be included much more in the cavity of the macrocycle than S-7. From the Job plots of the 1H NMR titration, it was found that both R-7 and S-7 formed a 1:1 complex with (1S, 2S)-5. The association constants of (1S,2S)-5-R-7 and (1R,2R)-6-S-7 complex were 2.24 × 104 M-1 and 1.16 × 104 M-1, respectively, demonstrating a different binding force when R -7 and S-7 interacted



with (1S,2S)-5, respectively. H 3C

H3 C O

O CH 2

CH 2

H N

NH

N H2 O

CH 2 Hd

O H3C

e

H

O

NH2

CH 2

O O

Hd

O H 3C

Hc

e

H H

c

O

O

H

H

a

a

S-Mandelic Acid (B)

R-Mandelic Acid (A)

Fig. 4. Upper: Schematic interaction of (1S,2S)-5 with R-7 (A) and with S-7 (B); Lower: Changes of 1H NMR spectra of (1S,2S)-5 with increasing R-7 in CDCl3. [(1S,2S)-5] = 3.0 mM, the number over the spectrum is the molar ratio of R-7 vs. (1S,2S)-5. The double-headed arrows indicated the NOE signals existing between two hydrogen atoms.

Δδ *[1S, 2S- 5]/([1S, 2S-5]+[S-7])

A Δδ *[ 1S, 2S-5]/([1S, 2S-5]+[R-7])

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0.016 0.012 0.008 0.004 0.000 0.000

0.002

0.004 [R-7]/M

0.006

B 0.010 0.008 0.006 0.004 0.002 0.000 0.000

0.002

0.004

0.006

[S-7]/M

Fig. 5. (A) Job plot for 1H NMR titration of (1S,2S)-5 (0.003 M) with R-7 in CDCl3. (B) Job plot for 1H NMR titration of (1S,2S)-5 (0.003 M) with S-7 in CDCl3. The 2D NOESY spectra of the mixture of (1S, 2S)-5 with the enantiomers of R-mandelic acid 7 showed distinct NOE signals between proton (Ha) of R-7 and phenyl proton (Hd) of (1S,2S)-5, Ha


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and He (Fig. S29), indicating that the phenyl ring of the acid was close to the phenoxy group. The NOE between the α-proton Hc of R-7 and proton He of the methoxy group of (1S, 2S)-5 was also observed, indicating that Hc was close to the phenoxy group in the complex. For the mixture of (1S, 2S)-5 with S-7, the only NOE signal was observed between He and Hc, which implied a weak interaction between (1S, 2S)-5 and S-7. This result also implied that R-7 went into the cavity of the macrocycle (1S, 2S)-5 deeper than S-7, which could restrict more intramolecular rotations and emit stronger fluorescence. Therefore, in addition to the acid-base interaction, the host-guest interaction of the macrocycle receptor also played a key role on its chiral recognition. As disclosed by FE-SEM and TEM, there truly existed an aggregation difference between the mixtures of (1S, 2S)-5 and the two enantiomers of the mandelic acid 7. The mixture of (1S,2S)-5 and S-7 in 7:13.5 THF/H2O showed almost no aggregates with uniform morphology (Fig. 6A) while the mixture of (1S,2S)-5 and R-7 formed nanospheres which filled up the FE-SEM images (Fig. 6B − 6C). TEM images (Fig. 6D − 6F) disclosed that the mixture of (1S, 2S)-5 with R-7 was composed of round spherical aggregates with diameter of 300 − 500 nm, being in accordance with the FE-SEM results.

Fig. 6 (A) FE-SEM image of (1S, 2S)-5 with S-7 in 7:13.5 THF/H2O; (B − C) FE-SEM image of (1S, 2S)-5 with R-7; (D − F) TEM image of (1S, 2S)-5 with R-7 in 7:13.5 THF/H2O. [(1S, 2S)-5] =



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[R-7] = [S-7] = 0.5 mM. In summary, the chiral TPE macrocycles bearing optical pure amine group (1S,2S)-5 and (1R,2R)-6 were synthesized and were found to discern the two enantiomers of acidic compounds as well as α-amino acids by enantioselective aggregation and AIE effect. Due to the cavity of the macrocycle and the probable host-guest interaction, not only the chiral acidic compounds but also the zwitterions α-amino acids could be enantioselectively recognized. This result demonstrates the great potential of a chiral AIE macrocycle as a fluorescence chiral receptor. EXPERIMENTAL SECTION Compound 2, 3, and 4 were synthesized according to our previous literature10b. Synthesis of compound 2 To a one-neck flask was added 1 (2.5 g, 6.4 mmol), hexamethylenetetramine (17.8 g, 0.127 mol) and TFA (70 mL) and the mixture was refluxed for about 2 h until starting materials 1 disappeared (monitored by TLC). The mixture was quenched with cold water and extracted with chloroform. The organic layer was washed with water and dried over Na2SO4. The solvent was evaporated under reduced pressure, and the residue was purified by flash column chromatography (silica gel, petroleum ether / ethyl acetate 4:1) to yield the desired bisformyl product 2 as a yellow solid (1.85 g, 65% yield). M. p. : 179.5 − 181.8 ℃; 1H NMR (CDCl3, 400 MHz) δ = 3.88 (s, 6H), 6.73 − 6.71 (d, J = 8.8 Hz, 2H), 7.03 − 7.01 (m, 4H), 7.15 − 7.10 (m, 6H), 7.229 − 7.223 (d, J = 2.4 Hz, 1H), 7.027 − 7.021 (d, J = 2.4 Hz, 1H), 7.474 − 7.468 (d, J = 2.4 Hz, 2H), 10.326 (s, 2H) ppm;

13

C NMR (CDCl3, 100 MHz) 55.6, 111.1, 124.3, 126.6, 127.9, 131.2, 131.2, 135.7, 137.7,

138.8, 141.6, 143.6, 160.5, 168.5 ppm. IR (KBr film): νmax = 3075.0, 3006.2, 2965.0, 1665.5, 2941.0, 2886.4, 1681.0, 1601.8, 1569.6, 1493.4, 1392.2, 1260.9, 1176.9, 1024.1, 756.3, 704.3


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cm-1. Synthesis of compound 3 To a one-neck flask was added 5:2 THF/C2H5OH (70 mL), 2 (1.76 g, 3.92 mmol) and NaBH4 (1.49 g, 39.2 mmol). The mixture was stirred at room temperature for about 7 h until 2 disappeared (monitored by TLC, 1:1 ethyl acetate/petroleum). After the solvent was removed by evaporation under reduced pressure, to the residue was added saturated NH4Cl aqueous solution and extracted with ethyl acetate. The combined organic phase was dried over anhydrous Na2SO4. The crude product was recrystallizated by chloroform and methanol to obtain compound 3 as a white solid (1.60 g, 90% yield). 1H NMR (CDCl3, 400 MHz) δ = 2.027 (s, 2H), 3.793 (s, 6H), 4.458 (s, 4H), 6.614 − 6.593 (d, J = 8.4Hz, 2H), 6.935 − 6.909 (m, 4H), 7.021 − 7.002 (m, 4H), 7.124 − 7.049 (m, 6H) ppm; 13CNMR (CDCl3, 100 MHz) 55.2, 61.9, 109.4, 126.1, 127.7, 128.1, 131.3, 131.9, 132.0, 135.9, 139.7, 139.7, 144.1, 156.0 ppm. IR (KBr film): νmax = 3415.6, 3064.7, 3024.1, 2943.2, 2929.5, 2871.4, 1603.1, 1499.2, 1440.3, 1380.7, 1292.2, 1244.6, 1027.0, 1001.0, 755.9, 698.4 cm-1. Synthesis of compound 4 To a chilled solution of 3 (1.71 g, 3.78 mmol) and pyridine (380 µL) in CH2Cl2 (30 mL) at 0 o

C was added dropwise a solution of SOCl2 (0.1 mL) in CH2Cl2 (30 mL) under stirring. The

mixture was allowed to stir at room temperature for 8 h. After removal of the solvent, toluene (20 mL) was added and the mixture was evaporated to dryness. The oily residue was extracted with CH2Cl2 for three times and the combined organic phases were washed with H2O followed with brine, and dried over Na2SO4. After the removal of the solvent, the crude product was purified by column chromatography to give 4 as a white solid (1.58 g, 85% yield).


1

H NMR (CDCl3, 400


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MHz) δ = 3.811 (s, 6H), 4.421 (s, 4H), 6.621 (d, J = 8.4Hz, 2H), 6.964 − 6.938 (dd, J = 2.0 Hz, J = 2.0 Hz, 2H), 7.019 − 6.987 (m, 6H), 7.109 − 7.074 (m, 6H) ppm; 13C NMR (CDCl3, 100 MHz) 41.5, 55.5, 110.0, 124.9, 126.3, 127.8, 131.2, 133.1, 133.9, 135.8, 138.9, 140.1, 143.9, 155.9 ppm. IR (KBr film): νmax = 3052.2, 2994.2, 2929.4, 1606.7, 1501.4, 1442.3, 1267.2, 1111.5, 1028.4, 815.5, 769.9 cm-1. Synthesis of compound (1S, 2S)-5 To a flask was added 4 (700 mg, 1.43 mmol), (1S,2S)-1,2-diphenyl-1,2-diaminoethane (1.20 g, 5.72 mmol), K2CO3 (600 mg, 4.29 mmol) and dry acetonitrile (30 mL). The mixture was refluxed for about 4 h until 4 disappeared (monitored by TLC, 1:3 ethyl acetate/petroleum). After acetonitrile was removed by evaporation under reduced pressure, to the residue was added dichloromethane. The organic phase was washed with water, dried over anhydrous Na2SO4, filtered, and evaporated to dryness under reduced pressure. The crude product was purified by flash column chromatography (silica gel, 4:1 ethyl acetate/petroleum) to give light yellow solid (1S, 2S)-5 (0.29g, 32% yield). M. p.: 168.0 − 171.1℃; [α]22D = +655; 1H NMR (CDCl3, 400 MHz) δ = 1.729 (s, 2H), 3.698 (s, 6H), 3.758 − 3.718 (d, J = 16Hz, 4H), 3.882 − 3.844 (d, J = 15.2 Hz, 2H), 6.510 − 6.488 (d, J = 8.8 Hz, 2H), 6.749 − 6.734 (d, J = 6.0 Hz, 4H), 7.003 − 6.976 (dd, J = 2.4Hz, 2.0 Hz, 2H), 7.206 − 7.124 (m, 19H) ppm; 13C NMR (CDCl3, 100 MHz) 45.6, 55.2, 61.3, 109.0, 126.3, 126.9, 127.2, 127.9, 129.0, 131.6, 132.8, 134.4, 136.1, 137.3, 145.2, 156.5 ppm. IR (KBr film): νmax = 3053.7, 3024.0, 2926.5, 2834.2, 1600.7, 1497.3, 1459.7, 1442.2, 1244.4, 1028.7, 922.8, 818.0, 699.5. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C44H41N2O2 629.3168; Found 629.3145. Synthesis of (1R, 2R)-6


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(1R,2R)-6 was prepared in the same procedure as that for (1S,2S)-5. Light yellow solid: 0.28g, 31% yield. [α]22D = −625; 1H NMR (CDCl3, 400 MHz) δ = 1.729 (s, 2H), 3.698 (s, 6H), 3.758 − 3.718 (d, J = 16Hz, 4H), 3.882 − 3.844 (d, J = 15.2 Hz, 2H), 6.510 − 6.488 (d, J = 8.8 Hz, 2H), 6.749 − 6.734 (d, J = 6.0 Hz, 4H), 7.003 − 6.976 (dd, J = 2.4 Hz, 2.0 Hz, 2H), 7.206 − 7.124 (m, 19H) ppm;

13

C NMR (CDCl3,100 MHz) 45.6, 55.2, 61.3, 109.0, 126.3, 126.9, 127.2, 127.9, 129.0,

131.6, 132.8, 134.4, 136.1, 137.3, 145.2, 156.5 ppm. IR (KBr film): νmax = 3054.0, 3024.0, 2921.6, 2834.6, 1597.4, 1497.2, 1453.6, 1288.6, 1244.6, 1121.4, 1029.6, 920.7, 817.5, 765.2, 700.0. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C44H41N2O2 629.3168; Found 629.3116. ACKNOWLEDGMENT The authors thank National Natural Science Foundation of China (21072067) for financial support and thank the Analytical and Testing Centre at Huazhong University of Science and Technology for measurement. AUTHOR INFORMATION Corresponding author *E-mail: [email protected] Notes The authors declare no competing financial interest. SUPPORTING INFORMATION 1

H and 13C NMR, IR, and HRMS spectra. This material is available free of charge via the Internet

at http://pubs.acs.org. REFERENCES (1) (a) Heo, J.; Mirkin, C. A. Angew. Chem. 2006, 118, 955 –958. Angew. Chem., Int. Ed. 2006, 45,



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

941 – 944. (b) Mei, X. F.; Wolf, C. J. Am. Chem. Soc 2004, 126, 14736 –14737. (c) Seifert, H. M.; Jiang, Y.-B.; Anslyn, E. V. Chem. Commun. 2014, 50, 15330-15332. (d) Jo, H. H.; Lin, C. Y.; Anslyn, E. V. Acc. Chem. Res. 2014, 47, 2212-2221. (2) Reviews for chiralrecognition: (a) Pu, L. Chem. Rev. 2004, 104, 1687–1716. (b) Hembury, G. A.; Borovkov, V. V.; Inoue, Y. Chem. Rev. 2008, 108, 1–73. (c) Zehnacker, A.; Suhm, M. A. Angew. Chem., Int. Ed. 2008, 47, 6970–6992. (d) Pu, L. Acc. Chem. Res. 2012, 45, 150–163. (e) Leung, D.; Kang, S. O.; Anslyn, E. V. Chem. Soc. Rev. 2012, 41, 448–479. (f) Accetta, A.; Corradini, R.; Marchelli, R. Top. Curr. Chem. 2011, 300, 175–216. (g) Zhang, X.; Yin, J.; Yoon, J. Chem. Rev. 2014, 114, 4918–4959. (h) You, L.; Zha, D.; Anslyn, E. V. Chem. Rev. 2015, DOI: 10.1021/cr5005524. (3) (a) Liu, H.-L.; Peng, Q.; Wu, Y.-D.; Chen, D.; Hou, X.-L.; Sabat, M.; Pu, L. Angew. Chem., Int. Ed. 2010, 49, 602–606. (b) Yu, S.; Pu, L. J. Am. Chem. Soc. 2010, 132, 17698–17700. (c) Chen, X.; Huang, Z.; Chen, S.-Y.; Li, K.; Yu, X.-Q.; Pu, L. J. Am. Chem. Soc. 2010, 132, 7297–7299. (d) Ferrand, Y.; Kendhale, A. M.; Kauffmann, B.; Grelard, A.; Marie, C.; Blot, V.; Pipelier, M.; Dubreuil, D.; Huc, I. J. Am. Chem. Soc. 2010, 132,7858–7859. (e) He, X.; Zhang, Q.; Wang, W.; Lin, L.; Liu, X.; Feng, X. Org. Lett. 2011, 13, 804–807. (4) (a) Pugh, V.; Hu, Q.-S.; Pu, L. Angew. Chem., Int. Ed. 2000, 39, 3638–3641. (b) Wang, Q.; Chen, X.; Tao, L.; Wang,

L.; Xiao, D.; Yu X. Q.; Pu, L. J. Org. Chem. 2007, 72, 97–101. (c) Liu,

H.-L.; Hou, X.-L.; Pu, L. Angew. Chem., Int. Ed. 2009, 48, 382 –385. (d) Wen, K.; Yu, S.; Huang, Z.; Chen, L.; Xiao, M.; Yu, X.; Pu, L. J. Am. Chem. Soc. 2015, 137, 4517–4524. (e) Wang, C.; Wu, E.; Wu, X.; Xu, X.; Zhang, G.; Pu, L. J. Am. Chem. Soc. 2015, 137, 3747–3750. (5) Articles for chiral fluorescent recognition of amino acids: (a) Huang, Z.; Yu, S.; Wen, K.; Yu,


Page 14 of 15

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


X.; Pu, L. Chem. Sci. 2014, 5, 3457–3462. (b) Yang, X.; Liu, X.; Shen, K.; Zhu, C.; Cheng, Y. Org. Lett. 2011, 13, 3510–3513. (c) Liu, H.-L.; Zhu, H.-P.; Hou, X.-L.; Pu, L. Org. Lett. 2010, 12, 4172-4175. (d) Jintoku, H.; Takafuji, M.; Odac, R.; Ihara, H. Chem. Commun. 2012, 48, 4881– 4883. (e) Liu, T.; Su, Y.; Song, H.; Lv, Y. Analyst 2013, 138, 6558–6564. (f) Aswathy, B.; Sony, G. Journal of Luminescence 2014, 154, 541 –548. (6) Li, F.; Li, L.; Yang, W.; Zheng, L.-S.; Zheng, Z.-J.; Jiang, K.; Lu, Y.; Xu, L.-W. Tetrahedron Lett. 2013, 54, 1584–1588. (7) (a) Hong, Y.; Lam, J. W. Y.; Tang, B. Z. Chem. Soc. Rev. 2011, 40, 5361−5388. (b) Wang, M.; Zhang, G.; Zhu, D.; Tang, B. Z. J. Mater. Chem. 2010, 20, 1858−1867. (c) Ding, D.; Li, K.; Liu, B.; Tang, B. Z. Acc. Chem. Res. 2013, 46, 2441–2453. (d) Feng, H.-T.; Zheng, Y.-S. J. Mater. Chem. C 2014, 2, 2353–2359. (8) Ng, J. C. Y.; Liu, J.; Su, H.; Hong, Y.; Li, H.; Lam, J. W. Y.; Wong , K. S.; Tang, B. Z. J. Mater. Chem. C 2014, 2, 78–83. (9) (a) Zheng, Y.-S.; Hu, Y.-J. J .Org .Chem. 2009, 74, 5660-5663. (b) Liu, N. N.; Song, S.; Zheng, Y.-S. Chem. Comm. 2012, 48, 4908-4910. (c) Li, D. M.; Zheng, Y.-S. J. Org. Chem. 2011, 76, 1100–1108. (d) Li, D. M.; Zheng, Y.-S. Chem. Commun. 2011, 47, 10139-10141. (e) Zheng, Y.-S.; Zhang, C. Org. Lett. 2004, 6, 1189-1192. (10) (a) Feng, H.-T.; Zheng, Y.-S. Chem. Eur. J. 2014, 20, 195 – 201. (b) Feng, H.-T.; Wang, J.-H.; Zheng, Y.-S. ACS Appl. Mater. Interfaces 2014, 6, 20067-20074. (c) Wang, J.-H.; Feng, H.-T.; Zheng, Y.-S. Chem. Commun. 2014, 50, 11407-11410. (d) Wang, J.-H.; Feng, H.-T.; Zheng, Y.-S. J. Org. Chem. 2014, 79, 5746–5751.


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