Cyclic Anion-Responsive π-Electronic Molecules That Overcome

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Letter pubs.acs.org/OrgLett

Cite This: Org. Lett. XXXX, XXX, XXX−XXX

Cyclic Anion-Responsive π‑Electronic Molecules That Overcome Energy Losses Induced by Conformation Changes Shunsuke Kaname,† Yohei Haketa,† Nobuhiro Yasuda,‡ and Hiromitsu Maeda*,† †

Department of Applied Chemistry, College of Life Sciences, Ritsumeikan University, Kusatsu 525-8577, Japan Research and Utilization Division, Japan Synchrotron Radiation Research Institute, Sayo 679-5198, Japan

‡

S Supporting Information *

ABSTRACT: Preorganized structures suitable for anion binding were prepared by introducing dipyrrolyldiketone BF2 complexes as acyclic anion-responsive π-electronic molecules into macrocycles. Pyrrole-inverted conformations, which typically present low stability in the case of acyclic derivatives, were obtained by covalent linkages through ring-closing olefin metathesis, exhibiting extremely high affinity for different anions.

T

with the pyrrole NH and bridging (meso) CH moieties (e.g., 1a−c, Figure 2), exhibiting planar, helical, and interlocked

he on-demand binding and release of ionic species by organic molecules are essential biotic processes, as in the case of ion channels.1 The conformation of host organic molecules whose ion-binding sites are not already suitably oriented for cooperative interactions needs to be rearranged for effective ion complexation.2 Such host molecules requiring drastic conformation changes prior to ion binding suffer significant energy losses compared to preorganized host molecules (Figure 1). Thus, the molecular design and synthesis of ion-binding molecules with preorganized structures are crucial for the preparation of stable ion complexes and their resulting assemblies and materials. Among the diverse anionbinding molecules reported thus far,3 dipyrrolyldiketone BF2 complexes effectively form anion complexes via interactions

Figure 2. Anion-binding modes of dipyrrolyldiketone BF2 complexes 1a−c with the theoretical relative stabilities (ΔE) of the pyrroleinverted forms and anion-binding constants (Ka).

geometries, and thus, serving as building subunits for ionpairing assembled structures.4−6 Even though large anionbinding constants (Ka, equal to exp(−ΔG/RT), where ΔG is the Gibbs free energy), have been measured for acyclic receptors 1a−c (e.g., 15 000 M −1 for Cl − by 1a in CH2Cl2),5d the pyrrole NH sites facing the carbonyl oxygens in the most stable conformations are required to turn to the opposite side for anion binding, resulting in pyrrole inversion. The stable conformation is determined by the dipole orientation of the constituting pyrrole and boron-bridged 1,3propanedione moieties. In fact, the preorganized conformations of 1a−c5a−c are 5.06, 3.20, and 7.51 kcal/mol higher in energy (ΔE), respectively, than their stable conformations, as estimated by density functional theory (DFT) calculations at the PCM-B3LYP/6-31+G(d,p) level in CH2Cl2 (Figure 2).7

Figure 1. Energy diagram of anion-binding processes with/without conformation changes in anion-responsive molecules (the energy standards are set as the anion-binding modes, and the relative stabilities include the energy of the free anion). © XXXX American Chemical Society

Received: April 10, 2018

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DOI: 10.1021/acs.orglett.8b01138 Org. Lett. XXXX, XXX, XXX−XXX

Letter

Organic Letters

characterization of 4a−e was performed by 1H and 13C NMR and MALDI-TOF-MS analyses. The differences in the conformations of 3a−e and 4a−e were determined by 1H NMR analysis in CDCl3. The pyrrole NH and meso-CH signals of, for example, 3b at 9.43 and 6.52 ppm, respectively, are shifted upfield in 4b to 8.84 and 6.07 ppm, respectively, after cyclization (Figure 4), as also observed for

The theoretical relative stability is correlated with the electrondonating and -withdrawing properties of the β-substituents. The Ka value is determined by two factors: the electrondonating and -withdrawing properties of the β-substituents and the stability of the pyrrole-inverted structures. In any cases, the pyrrole inversion results in energy losses during the anionbinding process. Pyrrole-inverted preorganized structures can be fabricated by introduction of anion-responsive units into macrocycles. Only one example has been reported thus far as a macrocycle derived from a meta-phenylene-bridged dimer, which exhibits extraordinarily high anion-binding ability and whose complex with Cl− was successfully isolated as the tetrabutylammonium (TBA) salt by silica gel column chromatography.5f However, the anion-free macrocycle could not be isolated because of the low stability of the resulting species, owing to electrostatic repulsion between the crowded hydrogen-bonding-donating pyrrole NH moieties. Potential building units for conversion into more stable macrocycles include the α-arylethynylsubstituted derivatives of dipyrrolyldiketone BF2 complexes (e.g., 2, Figure 3a), because their interaction sites are less

Figure 4. 1H NMR spectra of (a) 3b and (b) 4b in CDCl3. The lowintensity signals in 4b are derived from the presence of the minor presence of the cis isomer.

the other derivatives. Such an NH signal shift can be ascribed to dissociation of the hydrogen bonding with the carbonyl oxygen. The shift of the meso-CH may, in turn, be explained by ringcurrent effects of constituting pyrrole rings as suggested by the anisotropy of the current-induced density (ACID) calculations.11 It is also noteworthy that 4a−e exist as mixtures of trans and cis stereoisomers at the C=C units, which could not be separated. The ratio of trans and cis isomers (e.g., 84:16 for 4b) depends on the strap length and the synthetic reaction conditions. Selective hydrogenation of the C=C bond was unsuccessful after several attempts.12 The structures of macrocycles 4a−e and linear 3a were elucidated by single-crystal X-ray analysis (Figure 5).13,14

Figure 3. (a) α-Arylethynyl-substituted derivatives 2 and 3a−e and (b) synthesis of cyclic anion receptors 4a−e.

crowded and a variety of substituents can be introduced at the terminal aryl moieties.6 Based on such arylethynyl substitution, the synthesis and properties of macrocycles of dipyrrolyldiketone BF2 complexes were examined in this work. The olefin metathesis reaction is very effective for the formation of macrocycles. Meta-alkenyloxy (H2C=CH− CnH2n+1O)-substituted phenylethynyl derivatives 3a−e (n = 1−5, Figure 3a) were synthesized in 26−90% yields from the corresponding ene-yne-spacer units8 and α-diiodo 1b′5e by Sonogashira coupling in the presence of Pd(PPh3)4 and CuI in triethylamine (TEA) and THF (Figure 3b). The metasubstituents in these compounds are suitable for the formation of cyclic structures.9 In fact, linear 3a−e were converted into cyclic 4a−e in 40−86% yields by anion-template ring-closing olefin metathesis (RCM) in the presence of Grubb’s second catalyst and excess tetrabutylammonium chloride (TBACl) in dry CH2Cl2 (1.0 mM, rt, 2 days) (Figure 3b).10 In the absence of TBACl, only a trace amount of the macrocycle was obtained. The products were purified by extraction and silica gel column chromatography, which indicate their stabilities. The initial

Figure 5. Single-crystal structures (top and side views) of (a) 4a (only the independent structure composed of the trans isomer is shown), (b) 4b-plate (trans/cis ratio of 79:21), (c) 4b-needle (trans/cis ratio of 69:31), (d) 4c (trans/cis ratio of 54:46), (e) 4d (one of the independent structures), and (f) 4e (a minor disordered structure). The exact trans/cis ratios of 4d,e could not be estimated. Atom color code: brown, pink, yellow, green, blue, and red indicate carbon, hydrogen, boron, fluorine, nitrogen, and oxygen, respectively. B

DOI: 10.1021/acs.orglett.8b01138 Org. Lett. XXXX, XXX, XXX−XXX

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Organic Letters

nm, partially ascribed to the variations in their molecular geometries. The observed absorption spectra are consistent with the calculated time-dependent (TD)-DFT-based theoretical spectra (Figure 6b).7 Notably, the greater absorptions in the short wavelength region (382−389 nm) for the macrocycles are correlated with the pyrrole inversion, resulting in larger transition dipoles along the short axis in parallel with the B− meso-C unit. As also suggested by the TD-DFT calculations, the absorbance intensities at 382−389 nm relative to those at 513− 519 nm increase with decreasing alkene strap length. The anion-binding properties of 4a−e along with 3a−e were investigated by 1H NMR upon the addition of Cl− as a TBA salt in CD2Cl2 (1.0 mM) at 20 and −50 °C (Figure 7). In the

Evidently, 4a−e exhibited pyrrole-inverted cyclic structures. The ratios of trans and cis isomers in the crystals do not correlate with those revealed by 1H NMR in solution state. The single crystal of 4a includes two independent structures; one containing only the trans isomer, and a second one containing disordered trans and cis forms (74:26). In the latter independent structure of 4a, a CH2Cl2 molecule is located inside the macrocycle, where it interacts with the pyrrole NH and meso-CH moieties at N(−H)···Cl and C(−H)···Cl distances of 3.14/3.22 and 2.99 Å, respectively. Columnar structures are formed through π−π interactions between the planes of the pyrrole and diketone moieties with a distance of 3.63 Å. In contrast, 4b afforded two crystal polymorphs in the shape of plates and needles. The trans and cis ratios in the 4bplate and 4b-needle crystals are 79:21 and 69:31, respectively. In both crystal structures, a water molecule is located inside the macrocycle. In 4b-plate, the pyrrole NH and meso-CH groups interact with a water molecule at N(−H)···O and C(−H)··O distances of 3.11/3.12 and 3.31 Å, respectively, whereas, in the 4b-needle, the N(−H)···O and C(−H)··O distances are 3.10/ 3.30 and 3.20 Å, respectively. In addition, 4b-plate exhibits π−π stacking with distances of 3.49 Å between the pyrrole moieties and 3.76 Å between the pyrrole and phenylethynyl moieties. The 4b-needle forms columnar structures through weak interactions between the pyrrole ring and phenylethynyl moiety with a distance of 3.78 Å. On the other hand, 4c, whose trans and cis ratio is 54:46, forms columnar structures through π−π interactions and contains a water molecule inside the macrocycle. Furthermore, 4d,e were obtained as needle-shape crystals, and their packing structures are constructed by intermolecular hydrogen bonding via pyrrole N−H···F−B inside the macrocycles. The dihedral angles between the pyrrole rings and central six-membered ring of 4a−e varied within the range 5.26−24.77°. On the other hand, the optimized structures of 4a−e7 suggest that the trans and cis isomers of 4c show the smallest dihedral angles by 17.32° and 14.90°, respectively. The pyrrole N···N distances depend on the strap lengths. The N···N distances in the solid state were measured as 4.95 Å for the independent structure of 4a and as 4.85 and 4.95 Å in the other disordered structure. For 4b−e, the N···N distances are within the range 4.98−5.40 Å. In the optimized structures of 4a−e,7 the N···N distances were estimated to be in the range 5.07−5.34 Å. Therefore, the alkenyl chains in the crystals are less ordered than those in the optimized structures due to the crystal packing. Further examination of the cyclic structures was conducted by UV/vis absorption spectra in CH2Cl2 (Figure 6a). In contrast to the absorption maxima (λmax) of 3a−e in the range 526−529 nm, 4a−e show blue-shifted λmax values at 513−519

Figure 7. 1H NMR spectral changes for 4b (1.0 mM) in CD2Cl2 at 20 °C upon the addition of Cl− as a TBA salt.

case of 3a at −50 °C, the intensity of the signal of the pyrrole NH at 9.64 ppm decreased after the addition of Cl−, and new signals appeared at 11.68 and 12.34 ppm derived from interlocked [2 + 1]- and planar [1 + 1]-type complexes, respectively. As observed for other linear derivatives, pyrroleinverted processes induce slow anion binding, resulting in the detection of both the receptors and anion complexes in the NMR time scale.15 In contrast, the signals for 4a−e experienced gradual shifts upon Cl− binding, as no pyrrole inversion was required.16 In the case of 4b, for example, the pyrrole NH signals at 8.91/8.95 ppm and meso-CH signals at 6.15/6.17 ppm (for the trans and cis isomers, respectively) shifted downfield to 12.41/12.49 and 8.22 ppm, respectively, after the addition of Cl− (1.4 equiv) (Figure 7). Such observations are characteristic of fast anion binding by preorganized cyclic receptors. DFT calculations at the B3LYP/6-31+G(d,p) level supported the planar geometries of the [1 + 1]-type receptor− anion complexes of 4a−e.7 The anion-binding properties of the macrocycles 4a−e along with the linear 3a−e were examined by the changes in their UV/vis absorption spectra upon the addition of different anions as TBA salts in CH2Cl2 (Table 1). The obtained Ka values of 4a−e for Cl−, Br−, and CH3CO2− are much larger than those of 3a−e due to the preorganized cyclized structures of 4a−e. For Table 1. Binding Constants (Ka, 103 M−1) of 3b, as a Representative, and 4a−e for Cl−, Br−, and CH3CO2− as TBA+ Salts in CH2Cl2 at 20 °C

Figure 6. (a) UV/vis absorption normalized spectra of 4a−e (red, orange, green, blue, and purple, respectively) in CH2Cl2 and (b) TDDFT-based UV/vis absorption stick spectrum of 4a-trans at the B3LYP/6-31+G(d,p) level along with the observed spectrum (red) shown in (a).

Cl− Br− CH3CO2− C

3b

4a

4b

4c

4d

4e

2.5 0.6 100

4500 6400 29 000

1800 430 3700

1200 440 1400

790 250 3000

950 430 4400

DOI: 10.1021/acs.orglett.8b01138 Org. Lett. XXXX, XXX, XXX−XXX

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Organic Letters example, the Ka values for Cl− of 3b and 4b at 20 °C were estimated as 2500 and 1 800 000 M−1, respectively. It should be noted that any trans and cis effects on the Ka values were not considered in this study. The significant improvement of the anion-binding ability for the macrocycles is induced by the avoidance of the pyrrole-inversion process and the subsequent energy loss during anion binding. Based on the Ka values of 2 and 4b for Cl− at 20 °C, the corresponding ΔG values were estimated as −4.59 and −8.39 kcal/mol, respectively. Their difference, ΔΔG = 3.80 kcal/mol, is greater than the Gibbs free energy ΔG1 theoretically required for pyrrole inversion for 2 and comparable to the theoretical Gibbs free energy ΔG2 between the most stable form of 2 and the nonoptimized form obtained upon the removal of Cl− from the optimized 2·Cl− structure (ΔG1 = 2.87 kcal/mol and ΔG2 = 4.20 kcal/mol at the PCM-B3LYP/6-31+G(d,p) level in CH2Cl2 at 20 °C).17 The lower stability of the macrocycle compared to the geometry state with only pyrrole inversion is suitable for the more efficient anion binding (larger ΔΔG). A similar tendency was also observed in other binding systems for receptors and anions, except for CH3CO2−, which showed smaller ΔΔG values than ΔG1. Interestingly, 4a, with tightly linked straps and the largest Ka values of all the macrocycles, exhibits comparable Ka values for Cl− and Br−. These results suggest that the slightly distorted geometry of 4a affords a more suitable binding cavity for Br−. In contrast to linear receptors, the macrocycles display pyrrole-inverted conformations, as demonstrated by the small spectral changes upon anion binding. Anion complexes of π-electronic molecules are essential building units for ion-pairing assemblies in combination with cations. Single crystals of the Cl− complex of 4b as ion pairs with tetrapropylammonium (TPA) and TBA cations were obtained from 1:1 mixtures of 4b and the corresponding Cl− salts by vapor diffusion of n-octane into a 1,2-dichloroethane solution and n-hexane into a CH2Cl2 solution, respectively. The X-ray analysis revealed the formation of a [1 + 1]-type complex 4b·Cl− (Figure 8a,b(i)).13,14 The pyrrole NH and meso-CH moieties interact with the Cl− anion with average N(−H)···Cl− and C(−H)···Cl− distances of 3.24 and 3.43 Å for 4b·Cl−-TPA+ and 3.23 and 3.45 Å for 4b·Cl−-TBA+, respectively. In the

packing structures, 4b·Cl−-TPA+ and 4b·Cl−-TBA+ exhibit charge-by-charge assemblies comprising alternately stacking 4b· Cl− and the countercations along the b-axis (Figure 8a,b (ii)). In these assemblies, the distances between the mean-plane Cl− complexes are 7.96 and 7.72 Å for 4b·Cl−-TPA+ and 4b·Cl−TBA+, respectively, wherein the distances between Cl− and the neighboring nitrogen atoms of TPA+ (TPA-N) are 4.61 and 5.24 Å and those in the ion pair with TBA+ are 4.25 and 4.28 Å. In summary, cyclic anion receptors of dipyrrolyldiketone BF2 complexes with pyrrole-inverted conformations were synthesized by anion-template ring-closing olefin metathesis. The preorganized structures suitable for anion binding exhibit extremely high affinities for different anions compared to the corresponding linear derivatives. The cyclization strategy in this report overcomes the energy losses due to pyrrole inversion and, notably, provides more suitable conformations for anion binding. The anion-free pyrrole-inverted conformations, which had not been previously observed in solution, reveal the real nature of the anion-responsive molecules in terms of their stability, electronic state, and anion-binding properties. Based on these cyclic structures, anion-binding mechanically interlocked systems can be fabricated18 and further investigations are currently in progress.

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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.orglett.8b01138. Synthetic procedures, spectroscopic data, and theoretical study (PDF) Accession Codes

CCDC 1833178−1833186 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing [email protected], or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Hiromitsu Maeda: 0000-0001-9928-1655 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by JSPS KAKENHI Grant Numbers JP26288042 and JP18H01968 for Scientific Research (B) and JP26107007 for Scientific Research on Innovative Areas “Photosynergetics” and the Ritsumeikan Global Innovation Research Organization (R-GIRO) Project (2017−2022). Theoretical calculations were partially performed using the Research Center for Computational Science, Okazaki, Japan. We thank Prof. Atsuhiro Osuka, Dr. Koji Naoda, Dr. Shinichiro Ishida, and Mr. Takanori Soya, Kyoto University, for singlecrystal X-ray analysis; Dr. Ryohei Yamakado, Yamagata University, Prof. Hikaru Takaya, Kyoto University, and Dr. Kunihisa Sugimoto, JASRI/SPring-8, for synchrotron radiation

Figure 8. Single-crystal X-ray structures of (a) 4b·Cl−-TPA+ and (b) 4b·Cl−-TBA+ as (i) [1 + 1]-type Cl− complexes and (ii) ion-pairing assemblies. Only the trans form of 4b is observed in the crystal states. Atom color code in (i): brown, pink, yellow, yellow green (spherical), green, blue, and red indicate carbon, hydrogen, boron, chlorine, fluorine, nitrogen, and oxygen, respectively. The anion complex and cation parts in (ii) are presented in magenta and cyan colors, respectively. D

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(17) ΔG1 and ΔG2 were theoretically estimated based on the Gibbs free energies, which are temperature-dependent, of the calculated structures and not based on their electronic energies (heat of formation) related with ΔE. (18) The mixture of linear 3e and cyclic 4e (1 mM each) in the presence of TBACl (0.50 equiv) in CD2Cl2 at −50 °C showed a small 1 H NMR signal at 11.38 ppm probably derived from the pseudorotaxane-type 3e·4e·Cl− complex. The para-substituted derivative, bearing a binding site larger than that of 4e, exhibited a more evident signal ascribed to the corresponding pseudorotaxane. These pseudorotaxanes were also detected by Fourier transform ion cyclotron resonance (FT-ICR) ESI-MS (see also the SI).

single-crystal X-ray analysis (BL02B1 and BL40XU at SPring8:2016B0114, 2016B0123, 2017A1322, and 2017A1676); Prof. Yasuteru Shigeta, the University of Tsukuba, for help with the theoretical study; and Prof. Hitoshi Tamiaki, Ritsumeikan University, for various measurements.

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REFERENCES

(1) Pusch, M. In Ion Channels: From Structure and Function; Kew, J., Davies, C., Eds.; Oxford University Press: New York, 2010; pp 172− 182. (2) Selected book on ion binding: Supramolecular Chemistry: From Molecules to Nanomaterials, Gale, P. A., Steed, J. W., Eds.; Jon Wiley & Sons: Chichester, U.K., 2012. (3) Selected books on anion binding: (a) Supramolecular Chemistry of Anion; Bianchi, A., Bowman-James, K., García-España, E., Eds.; Wiley-VCH: New York, 1997. (b) Anion Sensing; Stibor, I., Ed.; Topics in Current Chemistry, Vol. 255; Springer: Berlin, 2005. (c) Sessler, J. L.; Gale, P. A.; Cho, W.-S. Anion Receptor Chemistry; RSC: Cambridge, U.K., 2006. (d) Anion Recognition in Supramolecular Chemistry; Gale, P. A., Dehaen, W., Eds.; Topics in Heterocyclic Chemistry, Vol. 24; Springer: Berlin, 2010. (e) Anion Coordination Chemistry; BowmanJames, K., Bianchi, A., García-España, E., Eds.; Wiley-VCH: New York, 2011. (4) (a) Haketa, Y.; Maeda, H. Chem. Commun. 2017, 53, 2894. (b) Haketa, Y.; Maeda, H. Bull. Chem. Soc. Jpn. 2018, 91, 420. (5) (a) Maeda, H.; Kusunose, Y. Chem. - Eur. J. 2005, 11, 5661. (b) Maeda, H.; Ito, Y. Inorg. Chem. 2006, 45, 8205. (c) Maeda, H.; Kusunose, Y.; Mihashi, Y.; Mizoguchi, T. J. Org. Chem. 2007, 72, 2612. (d) Maeda, H.; Terasaki, M.; Haketa, Y.; Mihashi, Y.; Kusunose, Y. Org. Biomol. Chem. 2008, 6, 433. (e) Maeda, H.; Haketa, Y. Org. Biomol. Chem. 2008, 6, 3091. (f) Haketa, Y.; Maeda, H. Chem. - Eur. J. 2011, 17, 1485. (6) (a) Yamakado, R.; Sakurai, T.; Matsuda, W.; Seki, S.; Yasuda, N.; Akine, S.; Maeda, H. Chem. - Eur. J. 2016, 22, 626. (b) Yamakado, R.; Sato, R.; Shigeta, Y.; Maeda, H. J. Org. Chem. 2016, 81, 8530. (c) Yamakado, R.; Ashida, Y.; Sato, R.; Shigeta, Y.; Yasuda, N.; Maeda, H. Chem. - Eur. J. 2017, 23, 4160. (7) Frisch, M. J. et al. Gaussian 09, revision D.01; Gaussian, Inc.: Wallingford, CT, 2013. See Supporting Information (SI) for full reference. (8) Ogi, S.; Sugiyasu, K.; Takeuchi, M. Bull. Chem. Soc. Jpn. 2011, 84, 40. (9) The para-substituted derivative was also synthesized, and the details are discussed in the SI. (10) Selected examples of anion-template RCM reactions: (a) Wisner, J. A.; Beer, P. D.; Drew, M. G. B.; Sambrook, M. R. J. Am. Chem. Soc. 2002, 124, 12469. (b) Evans, N. H.; Rahman, H.; Leontiev, A. V.; Greenham, N. D.; Orlowski, G. A.; Zeng, Q.; Jacobs, R. M. J.; Serpell, C. J.; Kilah, N. L.; Davis, J. J.; Beer, P. D. Chem. Sci. 2012, 3, 1080. (c) Robinson, S. W.; Mustoe, C. L.; White, N. G.; Brown, A.; Thompson, A. L.; Kennepohl, P.; Beer, P. D. J. Am. Chem. Soc. 2015, 137, 499. (11) Herges, R.; Geuenich, D. J. Phys. Chem. A 2001, 105, 3214. (12) Separation of the trans and cis isomers by chromatography was difficult. (13) See the SI for the crystal data. (14) For the synchrotron radiation measurements: (a) Yasuda, N.; Murayama, H.; Fukuyama, Y.; Kim, J. E.; Kimura, S.; Toriumi, K.; Tanaka, Y.; Moritomo, Y.; Kuroiwa, Y.; Kato, K.; Tanaka, H.; Takata, M. J. Synchrotron Radiat. 2009, 16, 352. (b) Yasuda, N.; Fukuyama, Y.; Toriumi, K.; Kimura, S.; Takata, M. AIP Conf. Proc. 2010, 1234, 147. (15) Slow equilibria of anion binding: Choi, K.; Hamilton, A. D. J. Am. Chem. Soc. 2003, 125, 10241. See also ref 5. (16) Fast equilibria of anion binding: (a) Li, Y.; Flood, A. H. Angew. Chem., Int. Ed. 2008, 47, 2649. (b) Gavette, J. V.; Mills, N. S.; Zakharov, L. N.; Johnson, C. A., II; Johnson, D. W.; Haley, M. M. Angew. Chem., Int. Ed. 2013, 52, 10270. E

DOI: 10.1021/acs.orglett.8b01138 Org. Lett. XXXX, XXX, XXX−XXX