Threading of an Inherently Directional Calixarene Wheel with Oriented

Aug 11, 2017 - The threading of monostoppered alkylbenzylammonium axles 7+ and 8+ with the calix[6]-wheel 3 can occur by both routes of entering the m...
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Threading of an Inherently Directional Calixarene Wheel with Oriented Ammonium Axles Pellegrino La Manna, Carmen Talotta,* Carmine Gaeta, Annunziata Soriente, Margherita De Rosa, and Placido Neri Dipartimento di Chimica e Biologia “A. Zambelli”, Università di Salerno, Via Giovanni Paolo II 132, I-84084 Fisciano, Salerno, Italy S Supporting Information *

ABSTRACT: The threading of monostoppered alkylbenzylammonium axles 7+ and 8+ with the calix[6]-wheel 3 can occur by both routes of entering the macrocycle 3 in the cone conformation: passage through the upper rim and the through the lower rim. Thus, under thermodynamic conditions, with both the axles 7+ and 8+, the two possible orientations of calix[2]pseudorotaxane, namely, endo-benzyl and endo-alkyl, are formed by a stereoselectivity controlled by the endo-alkyl rule. Interestingly, by 1H NMR monitoring of the threading process between 8+ and 3, we revealed two calix[2]pseudorotaxane isomers in which the calix-wheel adopts 1,2,3-alternate and cone conformations, which represent the kinetic and thermodynamic species, respectively. Finally, the synthesis of ammonium-based oriented calix[2]rotaxane is here described.

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INTRODUCTION

achiral components, in which the chirality arises by the presence of a rotationally asymmetrical macrocycle and a directional thread possessing nonequivalent ends (III and III′, Figure 1). In this work, the two enantiomeric rotaxanes were obtained by using a chiral stopper, to give two rotaxane diastereoisomers, which were substituted with an achiral one after their separation. Interlocked architectures with directional components are fundamental for the realization of molecular motors showing a unidirectional motion.7a In this regard, Leigh and co-workers have recently reported a small-molecule synthetic walker7d and a chemically fueled unidirectional circular motor.7e In the last 3 decades, calixarene macrocycles have found many applications as supramolecular hosts8c−h thanks to their synthetic and conformational versatility.8a,b They can be considered as wheels endowed with an inherent directionality.9 An oriented axle (e.g., 22+ and 4+, Figure 2) that is small enough to pass through both rims of a directional calix-wheel should generate two distinct orientational stereoisomeric pseudorotaxanes (IV and V, Figure 1). In these instances, a related point is to understand if the threading process occurs by the axle entering from the upper (also called exo or wide) or from the lower (also called endo or narrow) rim. Arduini and coworkers10 have shown that the directionality of the threading process of a triphenylureido-calix[6]arene wheel 1 (Figure 2) by an oriented monostoppered viologen axle 22+ is affected by the polarity of the solvent used. Interestingly, it was shown that in apolar solvents, such as C6D6, the threading process of 22+

Interpenetrated architectures, such as pseudorotaxanes, rotaxanes, and catenanes,1 beyond their potentiality as molecular machines,2 sensors,3 and catalysts,4 show fascinating structures that can present peculiar and unconventional forms of (stereo)isomerism. Special cases arise when structurally nonsymmetric (directional) threads and/or wheels are used. For example, Leigh and co-workers recently introduced the concept of sequence isomerism,5 in which two different rings may have different positions along a directional thread (I and II, Figure 1). More recently, Goldup and co-workers6 have reported the synthesis of a mechanically planar chiral rotaxane, composed by

Figure 1. Cartoon representation of some examples of (stereo)isomerism in (pseudo)rotaxane architectures generated by the use of oriented axles and/or directional wheels. © 2017 American Chemical Society

Received: June 5, 2017 Published: August 11, 2017 8973

DOI: 10.1021/acs.joc.7b01388 J. Org. Chem. 2017, 82, 8973−8983

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The Journal of Organic Chemistry

Figure 2. Oriented interpenetrated architectures based on the threading of directional calix-wheels.

occurs through the upper rim of 1,10c while in more polar solvents, such as CD3CN, the threading occurs from both rims,10c yielding a mixture of both IV and V stereoisomers (Figure 1). We have recently11 shown that a specific orientational stereoisomer11b can be obtained when oriented alkylbenzylammonium axles (e.g., 4+, Figure 2) are threaded through a directional calix[6]arene wheel (e.g., 3) by exploiting of the socalled “endo-alkyl rule”:12 threading of a directional alkylbenzylammonium axle through a hexaalkoxycalix[6]arene occurs with an endo-alkyl preference. By exploiting this “endo-alkyl rule”, we have recently reported the stereoselective synthesis of the first examples of calixarene-based oriented interlocked architectures: calix[2]catenane (Figure 2),11e calix[3]rotaxane,11d and handcuff calixrotaxane.12a Following this empirical rule, a neat preference for the endo-alkyl 5+ orientational pseudorotaxane stereoisomer (Figure 2) over the endo-benzyl 6+ one was observed.11b In a more general case, an endo-alkyl pseudorotaxane (e.g., 5+) could be formed by two different routes of the alkylbenzylammonium axle entering into the calix-wheel (e.g., 3): passage of the benzyl through the upper rim and passage of the alkyl through the lower rim (Figure 3). Very recently, we have reported an unidirectional threading motion11 based on the passage of the alkyl through the lower rim of alkylbenzylammonium axles with calix[5]-wheels.11 In this case, the benzyl group was too large to pass through the small calix[5]arene annulus. In order to get information on this threading directionality with the larger calix[6]arene wheel, we designed the monostoppered alkylbenzylammonium axles 7 + and 8 + (Schemes 1 and 2), bearing a free OH group, which could be exploited to isolate the corresponding calix[2]rotaxane after a subsequent stoppering reaction. Now, the question arises as to whether these monostoppered axles 7+ and 8+ are capable of a

Figure 3. Possible pathways for the formation of endo-alkyl 5+ 11b pseudorotaxane by threading 3 with 4+.

selective direction of threading: Do the axles enter from the upper or from the lower rim of 3? Will the stereochemistry of the corresponding pseudorotaxane still obey the endo-alkyl rule?

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RESULTS AND DISCUSSION Synthesis of TFPB− Salts of Monostoppered Axles 7+ and 8+. The synthetic pathway to 7+·TFPB− salt is outlined in Scheme 1.13 In detail, 4-tritylphenol 9 was treated with K2CO3 and reacted with 1,6-dibromohexane 10 to give monobromide 11. A mixture of 4-hydroxybenzaldehyde and 11 in acetonitrile, in the 8974

DOI: 10.1021/acs.joc.7b01388 J. Org. Chem. 2017, 82, 8973−8983

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The Journal of Organic Chemistry Scheme 1. Synthesis of Thread 7+ a

Reagents and conditions: (a) K2CO3, NaI, CH3CN, reflux, 18 h; (b) K2CO3, [18]crown-6, CH3CN, reflux, 18 h; (c) CHCl3, 2 h, rt → NaBH4, THF, 2 h, rt; (d) HCl, THF, rt, 1 h; (e) TFPBNa, dry MeOH, 25 °C, 18 h.

a

Scheme 2. Synthesis of Thread 8+ a

Reagents and conditions: (a) dry DMF, rt, 48 h; (b) K2CO3, CH3CN, reflux, overnight; (c) NH2NH2, EtOH, reflux, 2 h; (d) CHCl3, 2 h, rt → NaBH4, MeOH, 1 h, rt; (e) HCl, THF, 0 °C → rt, 1 h; (f) TFPBNa, dry MeOH, 25 °C, 24 h.

a

exchanged by treatment with NaTFPB in MeOH, to give 8+· TFPB− salt, bearing an external (with respect to the trityl stopper group) benzylammonium unit. Directional Threading of Calix[6]arene Wheel 3 with Axles 7+ and 8+. Initially, we studied the directionality of the threading of 3 with axle 7+. Two possible directional pseudo[2]rotaxanes are here expected, namely, endo-alkyl 20+ or endo-benzyl 20+ (Scheme 3). The 1H NMR spectrum of a 1:1 mixture of 7+ and 3 in CDCl3 at 25 °C (Figure 4) showed, immediately after mixing, the sharpening of all signals and the peculiar features of the presence of two stereoisomeric endo-alkyl and endo-benzyl 20+ pseudorotaxanes in a 98/2 ratio [see the Supporting Information (SI), Figure S39]. This means that the threading of 7+, bearing an external alkylammonium unit, with the calixwheel 3 takes place from both rims of the macrocycle. The preferential formation of the endo-alkyl 20+ stereoisomer, in

presence of K2CO3 and 18-crown[6], was refluxed for 18 h to give aldehyde 12. This compound was then coupled with 6amino-1-hexanol, directly reduced with NaBH4, and treated with HCl/MeOH to give the chloride salt 13. Finally, counterion exchange with NaTFPB led to the formation of 7+·TFPB− salt, bearing an external (with respect to the trityl stopper group) alkylammonium unit. The synthetic pathway to 8+·TFPB− salt is outlined in Scheme 2.13 The reaction of potassium phthalimide 14 with 1,6-dibromohexane 10, in DMF as solvent, led to the formation of monobromide 15. Compound 15 was then reacted with 4tritylphenol 9 in the presence of K2CO3 to give 16, which was reacted with hydrazine to afford the primary amine 17 in almost quantitative yield. Derivative 17 was reacted with aldehyde 18 to give the corresponding imine, which was directly reduced with NaBH4 and treated with HCl to give the secondary ammonium chloride salt 19. The counteranion of 19 was then 8975

DOI: 10.1021/acs.joc.7b01388 J. Org. Chem. 2017, 82, 8973−8983

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The Journal of Organic Chemistry Scheme 3. Formation of the Oriented endo-Alkyl and endo-Benzyl 20+ Calix[2]pseudorotaxanes

Figure 4. Significant portions of the 1H NMR spectra (400 MHz, CDCl3, 298 K) of (a) 3 and (b) a 1:1 mixture (3.0 × 10−3 M) of 3 and 7+·TFPB− immediately after mixing.

Figure 5. DFT-optimized structures16 of the oriented endo-alkyl (left) and endo-benzyl (right) 20+ calix[2]pseudorotaxanes [B3LYP/631G(d,p) level of theory and using Grimme’s dispersion corrections (IOp(3/124 = 3)].15

accordance with the endo-alkyl rule,12 occurs by passage through the lower rim of calix-wheel 3. The NMR spectrum of the 1:1 mixture in Figure 4b remained unchanged after 12 h at 55 °C, thus showing that the system has reached an equilibrium immediately after the mixing of 3 and 7+ in CDCl3. The apparent association constant for the complex, calculated by means of integration of the slowly exchanging 1H NMR signals, was 3.5 × 102 M−1 (SI, page S21).14 DFT calculations (Figure 5) at the B3LYP/6-31G(d,p) level of theory using Grimme’s dispersion corrections [IOp(3/ 124 = 3)]15 indicated the greater stability of the endo-alkyl 20+ stereoisomer over the endo-benzyl one. In detail, endo-alkyl 20+ was stabilized by two H-bonding interactions (Figure 5) between the ammonium group of 7+ and the oxygen atoms of the calix-wheel 3, with an average N···O distance of 3.02 Å and an average N−H···O angle of 159.5°.16 Four additional C− H···π interactions were detected between the α and β

methylene groups of the alkyl chain of 7+ inside the calix cavity and the aromatic rings of 3,16 with an average C− H···πcentroid distance of 3.16 Å16,17 and an average C− H···πcentroid angle of 155°.16 As concerns the DFT-optimized structure of the endo-benzyl 20+ pseudorotaxane (Figure 5, right), two H-bonding interactions were detected between the NH2+ group of 7+ and the oxygen atoms of 3, with a longer average distance of 3.15 Å (with respect to that found in endoalkyl 20+ stereoisomer of 3.02 Å) and an average angle of 157°.16 Finally, two aromatic C−H···π interactions were observed between the aromatic C−H of 7+ and the aromatic rings of calix-wheel 3, with an average distance C−H···πcentroid of 2.97 Å and an average C−H···πcentroid angle of 155.0°.16,17 At this point we moved our attention to the threading of 3 with axle 8+. Also in this instance, two oriented pseudorotaxane 8976

DOI: 10.1021/acs.joc.7b01388 J. Org. Chem. 2017, 82, 8973−8983

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The Journal of Organic Chemistry stereoisomers, namely, endo-alkyl and endo-benzyl 21+, could be formed (Figure 6).

formation of pseudorotaxane 21+1,2,3 (Scheme 4) in which the calix-wheel adopts a 1,2,3-alternate conformation.18 After Scheme 4. Mechanism for the Formation of the Oriented endo-Alkyl and endo-Benzyl 21+cone Calix[2]pseudorotaxanes by Threading of 8+ with 3

Figure 6. Drawing of the oriented endo-alkyl and endo-benzyl 21+ calix[2]pseudorotaxanes that could be formed by threading of 3 with axle 8+.

Interestingly, immediately after mixing 3 with 8+ in CDCl3, the 1H NMR analysis revealed the presence of shielded signals at negative values of chemical shifts (Figure 7b) indicative of the formation of a pseudorotaxane. In addition, a close inspection of the ArCH2Ar region revealed the presence of three AX systems (green in Figure 7b) compatible with the

equilibration of the mixture of 3 and 8+ in CDCl3 at 55 °C for 12 h, the signals of 21+1,2,3 disappeared while those of endoalkyl 21+cone and endo-benzyl 21+cone (Scheme 4 and Figure 7c,d) emerged. Interestingly, 1D and 2D NMR studies16 indicated that the oriented pseudorotaxane endo-alkyl 21+cone was preferentially formed over endo-benzyl 21+cone in a 98/2 ratio (Scheme 4).16 The above NMR spectra remained unchanged after 24 h at 55 °C, thus showing that the system had reached the equilibrium condition. A plausible explanation of these results is based on the initial formation of the kinetically favored pseudorotaxane 21+1,2,3 (Scheme 4). Indeed, the 1,2,3-alternate conformation of free 3 is a preferred conformation in solution, as evidenced by VT NMR studies (see the SI,16 pages S35−S38). Therefore, the threading of 31,2,3 by 8+ is faster than that of 3cone (Scheme 4) At this point, the formation of the two 21+cone pseudorotaxanes from 21+1,2,3 could take place through two possible routes. First, a dethreading of axle 8+ from 21+1,2,3 can occur and a subsequent rethreading from the lower and upper rim of 3cone, would take place to give endo-benzyl 21+cone and endo-alkyl 21+cone, respectively (Scheme 4). Second, a mechanism for the conversion of 21+1,2,3 to 21+cone (Scheme 4) based on a through-the-annulus reorganization of 3 could be envisioned. However, this latter mechanism can be ruled out because we have previously demonstrated that the presence of an ammonium axle inside the cavity of 3 (impedes) prevents the through-the-annulus passage of both the hexyl chains and the tert-butyl groups.13b In conclusion, under thermodynamic control, after 12 h at 55 °C, the pseudorotaxane 21+1,2,3

Figure 7. Significant portions of the 1H NMR spectra (400 MHz, CDCl3, 298 K) of (a) 3 and a 1:1 mixture (3.0 × 10−3 M) of 3 and 8+ (b) immediately after mixing and (c) after 12 h at 55 °C. (d) Enlargement of the 1H NMR and COSY sections (between 4.2 and 5.1 ppm) of the mixture in part c; the AX system for ArH protons of the shielded endo-cavity benzylammonium unit of the pseudorotaxane endo-benzyl 21+ is marked in magenta. 8977

DOI: 10.1021/acs.joc.7b01388 J. Org. Chem. 2017, 82, 8973−8983

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The Journal of Organic Chemistry initially formed is consumed in favor of the more stable 21+cone only through a dethreading/rethreading mechanism (Scheme 4). The preferential formation of endo-alkyl 21+cone stereoisomer was indicated by the presence in the 1H NMR spectrum (Figure 7c) of the typical signature at highfield negative values (α, β, γ, and δ protons, in red) characteristic of an endocomplexation of the alkyl chains of 8+. The apparent association constant for endo-alkyl 21+cone, calculated by integration of its slowly exchanging 1H NMR signals,16 was 5.5 × 102 M−1.16 The presence of endo-benzyl 21+cone was indicated by the expected upfield AX system between 4.0 and 5.0 ppm (see the insets in Figure 7d) of ArH protons of the shielded endo-cavity benzylammonium unit (in magenta in Scheme 3 and Figure 7d). All the above results clearly indicate that the monostoppered alkylbenzylammonium axle 8+ is able to thread the inherently directional calix[6]arene wheel 3 by entering from both rims (upper and lower) and that under thermodynamic conditions the endo-alkyl pseudorotaxane prevails in accordance with the known endo-alkyl rule. Summarizing, the formation of pseudorotaxane endo-alkyl 21+cone occurs by passage through the upper rim of calix-wheel 3. DFT calculations at the B3LYP/6-31G(d,p) level of theory using Grimme’s dispersion corrections [IOp(3/124 = 3)]15 indicated a greater stability of the endo-alkyl 21+cone over the endo-benzyl one. A close inspection of the optimized endo-alkyl 21+cone structure (Figure 8, left) reveals the presence of two H-

wheel 3 with an average N···O distance of 3.0 Å and a narrower N−H···O angle of 152.3°.16 In addition, two aromatic C−H···π interactions were detected between the aromatic ring of 8+, as C−H donor, and the aromatic rings of the calix-wheel 3, as C− H acceptors, with an average distance C−H···πcentroid of 3.10 Å and an average C−H···πcentroid angle of 145.8°.16 Synthesis of Oriented Calix[2]rotaxanes. The treatment of the mixture of the two pseudorotaxanes endo-alkyl and endobenzyl 20+ with 4-triphenylmethylphenylisocyanate gave the oriented [2]rotaxanes endo-alkyl 22+ and endo-benzyl 22+ in 13% total yield, in addition to the free stoppered axle (Scheme 5). Scheme 5. Synthesis of the Oriented Calix[2]rotaxanes 22+ a

a Reagents and conditions: (a) Di-n-butyltindilaurate, 4-triphenylmethylphenylisocyanate, dry CHCl3, 55 °C, 72 h.

The isomeric mixture of endo-alkyl and endo-benzyl 22+ was identified by 1D and 2D16 NMR spectroscopy but not separated by chromatography. Integration of the 1H NMR signals of the two isomeric rotaxane revealed a 96/4 endo-alkyl/ endo-benzyl ratio. The presence of the endo-alkyl 22+ rotaxane was confirmed by typical shielded resonances between 1.0 and −1.0 ppm in the 1H NMR spectrum (Figure 9). Analogously, the presence of the endo-benzyl 22+ stereoisomer was proved by the presence of the typical upfield AX system between 4.0 and 5.0 ppm (in magenta in Figure 9b) for ArH protons of the shielded endo-cavity benzylammonium unit. In a similar way, the mixture of endo-alkyl 21+cone and endobenzyl 21+cone pseudorotaxanes, obtained after equilibration, was reacted with 4-triphenylmethylphenylisocyanate (Scheme 6) to give directional endo-alkyl and endo-benzyl 23+ calix[2]rotaxanes (Scheme 6) in 39% total yield, in addition to the free stoppered axle. The isomeric mixture of endo-alkyl and endobenzyl 23+ was identified by 1D and 2D16 NMR spectroscopy, but not separated by chromatography. Integration of their 1H NMR signals indicated a 97/3 ratio between endo-alkyl and endo-benzyl 23+ stereoisomers. The presence of endo-alkyl 23+ stereoisomer was indicated by the typical signature at high-field negative values (in red, α, β, γ, and δ, from 1.0 to −1.0 ppm) of

Figure 8. DFT-optimized structures of the oriented endo-alkyl (left) and endo-benzyl (right) 21+ calix[2]pseudorotaxanes [B3LYP/631G(d,p) level of theory and using Grimme’s dispersion corrections (IOp(3/124 = 3)].15

bonds between the ammonium group of the axle 8+ and the oxygen atoms of the calix-wheel 3, with an average N···O distance of 3.0 Å and an average N−H···O angle of 159.2°.16 An extra stabilization of the endo-alkyl 21+cone structure was brought by C−H···π interactions17 between the α and β methylene groups of the alkyl chain of 8+ inside the calix cavity and aromatic rings of 3,16,17 with an average C−H···πcentroid distance of 3.25 Å16,17 and an average C−H···πcentroid angle of 160°.16,17 A similar analysis of the DFT-optimized structure of endo-benzyl 21+cone structure (Figure 8, right) revealed the presence of two H-bonding interactions between the ammonium group of 8+ and the oxygen atoms of the calix8978

DOI: 10.1021/acs.joc.7b01388 J. Org. Chem. 2017, 82, 8973−8983

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Figure 9. (a) Significant portion of the 1H NMR spectrum of 22+ (600 MHz, CDCl3, 298 K). (b) Enlargement of the 4.0−5.0 ppm section of the 1H NMR spectrum in part a; the signals of the oriented [2]rotaxane endo-benzyl 22+ are marked in magenta and in blue.

the 1H NMR spectrum (Figure 10a), which is characteristic of an endo-cavity alkylammonium moiety. A close inspection of the 1D and 2D NMR spectra16 also revealed the presence of the endo-benzyl 23+ rotaxane by the expected upfield AX system between 4.0 and 5.0 ppm (in magenta, Figure 10b) for ArH protons of the shielded endocavity benzylammonium unit. This was confirmed by an AX system attributable to the ArCH2Ar groups of the calix-wheel of endo-benzyl 23+ rotaxane (in blue, Figure 10b).

Figure 10. (a) Relevant portions of the 1H NMR spectra (600 MHz, CDCl3, 298 K) of [2]rotaxane endo-alkyl 23+. (b) Enlargement of the 4.0−5.0 ppm section of the 1H NMR spectrum in part a; the signals of the oriented endo-benzyl 23+ [2]rotaxane are marked in magenta and in blue.

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oriented calix[2]pseudorotaxanes, namely, endo-benzyl and endo-alkyl, are obtained for both 7+ and 8+ axles. Under those conditions, the stereoselectivity is controlled by the endo-alkyl rule with the observed prevalence of the endo-alkyl stereoisomer. Interestingly, in the threading of 3 with 8+, two calix[2]pseudorotaxane isomers are observed in which the calixwheel adopts a 1,2,3-alternate and a cone conformation, which

CONCLUSIONS The threading of calix[6]arene wheel 3 with alkylbenzylammonium axles can occur by both of the two possible routes of entering: passage through the upper rim and through the lower rim. Under thermodynamic conditions, the two possible Scheme 6. Synthesis of the Oriented Calix[2]rotaxanes 23+a

a

Reagents and conditions: (a) Di-n-butyltindilaurate, 4-triphenylmethylphenylisocyanate, dry CHCl3, 55 °C, 72 h. 8979

DOI: 10.1021/acs.joc.7b01388 J. Org. Chem. 2017, 82, 8973−8983

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The Journal of Organic Chemistry

pressure and the crude product was purified by column chromatography (SiO2, CH2Cl2) to give derivative 12 (0.28 g, 0.52 mmol, 50%) as a yellow oil. 1H NMR (250 MHz, CDCl3, 298 K): δ 1.82−1.83 (overlapped, 8H), 3.95 (t, J = 6.5 Hz, 2H), 4.05 (t, J = 6.3 Hz, 2H), 6.76 (d, J = 8.6 Hz, 2H), 6.98 (d, J = 8.6 Hz, 2H), 7.09 (d, J = 8.6 Hz, 2H), 7.21 (overlapped, 15H), 7.82 (d, J = 8.75 Hz, 2H), 9.88 (s, 1H). 13 C NMR (63 MHz, CDCl3, 298 K): δ 26.1, 29.2, 29.4, 64.5, 67.8, 68.4, 113.4, 114.9, 126.0, 127.6, 130.0, 131.3, 132.2, 132.3, 139.0, 147.2, 157.1, 164.4, 191.0. Anal. Calcd for C38H36O3: C, 84.41; H, 6.71. Found: C, 84.45; H, 6.72. Synthesis of Derivative 13. A solution of derivative 12 (0.27 g, 0.50 mmol) and derivative 6-amino-1-hexanol (0.06 g, 0.50 mmol) in CHCl3 was stirred for 2 h at room temperature. Solvent removal was performed in vacuo, to give the imine intermediate as a white solid in a quantitative yield, which was used in the next step without further purification. The imine was dissolved in THF (40 mL), NaBH4 (0.39 g, 10.2 mmol) was added at 0 °C, and then the mixture was allowed to warm at room temperature. The mixture was kept stirring for 2 h and the solvent was removed under reduced pressure. The residue was partitioned between AcOEt (50 mL) and an aqueous saturated solution of NaHCO3 (60 mL). The organic layer was dried over Na2SO4 and the solvent was removed under reduced pressure to give amine derivative (0.31 g, 0.49 mmol, 98%) as a yellow solid. The secondary amine derivative (0.31 g, 0.49 mmol) was dissolved in THF (40 mL) at room temperature and then an aqueous solution of HCl (37% w/w, 0.2 mL) was added dropwise. The mixture was kept stirring for 1 h and then solvent was removed under reduced pressure. The residue was dissolved in hot CH3CN. A white precipitate was formed when the solution was cooled at room temperature, and it was collected by filtration, washed with CH3OH, and dried under vacuum to give ammonium chloride derivative 13 (0.21 g, 0.31 mmol, 63% compared to amine intermediate) as a white solid. Mp: 101−102 °C. 1 H NMR (400 MHz, CDCl3, 298 K): δ 1.37−1.40 (overlapped, 4H), 1.55−1.60 (overlapped, 8H), 1.82−1.84 (overlapped, 4H), 2.66 (t, J = 7.2 Hz, 2H), 3.64 (t, J = 6.4 Hz, 2H), 3.77 (s, 2H), 3.95−3.99 (overlapped, 4H), 6.80 (d, J = 8.4 Hz, 2H), 6.88 (d, J = 8.4 Hz, 2H), 7.12 (d, J = 8.4 Hz, 2H), 7.21−7.29 (overlapped, 17H). 13C NMR (100 MHz, CDCl3, 298 K): δ 26.0, 27.0, 29.3, 29.4, 29.5, 29.8, 32.7, 48.9, 53.2, 62.7, 64.4, 67.8, 68.0, 113.3, 114.5, 125.9, 127.5, 129.7, 131.2, 138.9, 147.2, 157.1, 158.4. Anal. Calcd for C44H52ClNO3: C, 77.91; H, 7.73; N, 2.06. Found: C, 77.95; H, 7.72; N, 2.05. Synthesis of Derivative 7+·TFPB− . Ammonium chloride derivative 13 (0.12 g, 0.18 mmol) and sodium tetrakis[3,5bis(trifluoromethyl)phenyl]borate (0.18 g, 0.20 mmol) were dissolved in dry MeOH (50 mL). The solution was stirred for 18 h in the dark and then the solvent was removed and deionized water was added, obtaining a light brown precipitate that was filtered off and dried under vacuum to give thread 8+·TFPB− (0.17 g, 0.11 mmol, 61%) as a brown solid. Mp: >105 °C (dec); 1H NMR (250 MHz, CDCl3, 298 K): δ 1.39−1.56 (overlapped, 6H), 1.53−1.84 (overlapped, 10H), 3.02 (m, 2H), 3.69 (m, 2H), 3.96−3.99 (overlapped, 6H), 6.78 (d, J = 8.4 Hz, 2H), 6.92 (d, J = 8.4 Hz, 2H), 7.21−7.27 (overlapped, 19H), 7.56 (s, 4H), 7.72 (s, 8H). 13C NMR (100 MHz, CDCl3, 298 K): δ 23.9, 25.1, 26.0, 29.2, 29.4, 29.7, 47.4, 52.8, 63.0, 64.5, 67.9, 68.4, 113.4, 116.0, 117.8, 119.9, 122.0, 123.8, 125.6, 126.1, 127.5, 127.61, 127.6, 127.7, 129.0, 129.3, 130.9, 131.3, 132.4, 135.0, 139.2, 147.2, 157.2, 161.4, 161.7, 162.0, 162.4. Anal. Calcd for C76H64BF24NO3: C, 60.61; H, 4.28; N, 0.93. Found: C, 60.64; H, 4.26; N, 0.91. Synthesis of Compound 16. To a suspension of 9 (1.93 g, 5.72 mmol) in CH3CN (100 mL) was added K2CO3 under stirring (0.99 g, 7.16 mmol). The mixture was refluxed for 1 h and then derivative 15 (1.85 g, 5.96 mmol) was added and mixture was refluxed for 12 h. After concentration under vacuum, the mixture was partitioned between CH2Cl2 (120 mL) and water (100 mL) and then the organic layer was dried over Na2SO4, filtered, and evaporated under reduced pressure to give derivative 16 (3.12 g, 5.49 mmol, 96%). Mp: 78−79 °C. 1H NMR (400 MHz, CDCl3, 298 K): δ 1.40−1.55 (overlapped, 4H), 1.69−1.75 (overlapped, 4H), 3.66−3.71 (m, 2H), 3.89−3.92 (m, 2H), 6.72−7.75 (m, 2H), 7.05−7.08 (m, 2H), 7.16−7.26 (overlapped, 15H), 7.68−7.70 (m, 2H), 7.82−7.84 (m, 2H). 13C NMR (100 MHz,

represent the kinetic and thermodynamic species, respectively. In fact, the preferred 1,2,3-alternate conformer of 3 is quickly threaded by 8+ to give the calix[2]pseudorotaxane 21+1,2,3. Upon equilibration, this initially formed pseudorotaxane is consumed in favor of the more stable 21+cone only via a dethreading/rethreading mechanism. The control of the directionality of the threading of 3 with 7+ and 8+ is a prerequisite to the stereoselective synthesis of the first examples of ammonium-based oriented calix[2]rotaxanes 22+ and 23+. The stereoselective synthesis of these oriented interpenetrated architectures could allow the design of novel and intriguing calixarene-based molecular machines with expanded properties or functions.

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EXPERIMENTAL SECTION

General Information. ESI(+)-MS measurements were performed on a Micromass Bio-Q triple quadrupole mass spectrometer equipped with electrospray ion source, using a mixture of H2O/CH3CN (1:1) and 5% HCOOH as solvent. Flash chromatography was performed on Merck silica gel (60, 40−63 μm). All chemicals were reagent grade and were used without further purification. Anhydrous solvents were purchased from Aldrich. When necessary compounds were dried in vacuo over CaCl2. Reaction temperatures were measured externally. Reactions were monitored by TLC on Merck silica gel plates (0.25 mm) and visualized by UV light or by spraying with H2SO4−Ce(SO4)2 or phosphomolybdic acid. Derivatives 3,11b 15,19 1813b were synthesized according to literature procedures. NMR spectra were recorded on a Bruker Avance-600 spectrometer [600 (1H) and 150 MHz (13C)], Bruker Avance-400 spectrometer [400 (1H) and 100 MHz (13C)], Bruker Avance-300 spectrometer [300 (1H) and 75 MHz (13C)], or Bruker Avance-250 spectrometer [250 (1H) and 63 MHz (13C)]; chemical shifts are reported relative to the residual solvent peak [CHCl3, δ 7.26; CDCl3, δ 77.23; CD3OH, δ 4.87; CD3OD, δ 49.0; (CD3)2CO]. Standard pulse programs, provided by the manufacturer, were used for 2D NMR experiments, COSY-45, HSQC, and ROESY. COSY-45 spectra were taken using a relaxation delay of 2 s with 30 scans and 170 increments of 2048 points each. HSQC spectra were performed with the gradient selection, sensitivity enhancement, and phase-sensitive mode using an Echo/AntiechoTPPI procedure. Typically, 20 scans with 113 increments of 2048 points each were acquired. Synthesis of Derivative 11. K2CO3 (2.05 g, 14.8 mmol) and NaI (catalytic amounts) were added to a solution of derivative 9 (1.00 g, 2.97 mmol) in CH3CN (180 mL). The mixture was stirred for 30 min and then 1,6-dibromohexane 10 (1.45 g, 5.94 mmol, 0.91 mL) was added. The mixture was refluxed for 18 h. The solution was cooled at room temperature and the solvent evaporated under reduced pressure. The residue was partitioned between a 1 M solution of HCl (150 mL) and CH2Cl2 (150 mL), and the organic layer was washed successively with H2O and then dried over Na2SO4. Removal of the solvent under reduced pressure gave the crude product, which was precipitated in hexane. Derivative 11 was obtained as a white solid (0.99 g, 2.00 mmol, 67%), which was sufficiently pure for subsequent synthetic manipulations. Mp: 85−86 °C. 1H NMR (250 MHz, CDCl3, 298 K): δ 1.50−1.52 (overlapped, 4H), 1.79−1.92 (overlapped, 4H), 3.42 (t, J = 6.1 Hz, 2H), 3.94 (t, J = 6.2 Hz, 2H), 6.77 (d, J = 8.1 Hz, 2H), 7.09 (d, J = 8.1 Hz, 2H), 7.18−7.26 (overlapped, 15H). 13C NMR (100 MHz, CDCl3, 298 K): δ 25.6, 28.2, 29.4, 33.0, 34.1, 64.6, 67.8, 113.5, 126.1, 127.7, 131.4, 132.5, 139.1, 147.3, 157.3. Anal. Calcd for C31H31BrO: C, 74.54; H, 6.26. Found: C,74.63; H, 6.15. Synthesis of Derivative 12. Derivative 11 (0.13 g, 1.04 mmol) was dissolved in CH3CN (80 mL), and K2CO3 (0.55 g, 4.00 mmol), [18]crown-6 (catalytic amounts), and p-hydroxybenzaldehyde (0.52 g, 1.04 mmol) were added to the solution.The resulting mixture was refluxed for 18 h, the solvent was evaporated under reduced pressure, and the reaction residue was partitioned between HCl 1 M (40 mL) and AcOEt (60 mL). The organic layer was washed with deionized H2O and dried over Na2SO4. The solvent was removed under reduced 8980

DOI: 10.1021/acs.joc.7b01388 J. Org. Chem. 2017, 82, 8973−8983

Article

The Journal of Organic Chemistry CDCl3, 298 K): δ 25.9, 26.8, 28.7, 29.3, 38.1, 64.4, 67.7, 113.3, 114.4, 123.3, 126.0, 127.5, 131.3, 132.3, 132.6, 134.0, 138.9, 147.2, 157.1, 168.7. Anal. Calcd for C39H35NO3: C, 82.80; H, 6.24; N, 2.48. Found: C, 82.86; H, 6.25; N, 2.50. Synthesis of Compound 17. A solution of derivative 16 (1.45 g, 2.64 mmol) and hydrazine (150 mmol, 24.8 mL, 50−60% v/v solution in H2O) in EtOH was refluxed for 2 h. The solution was cooled at room temperature and H2O (100 mL) was added. The product was extracted with CH2Cl2 (3 × 100 mL), and the organic layers were collected and dried over Na2SO4, filtered, and evaporated under reduced pressure to give derivative 17 as a white solid (1.14 g, 2.61 mmol, 99%) or as a yellow oil. 1H NMR (300 MHz, CDCl3, 298 K): δ 1.38−1.45 (overlapped, 6H), 1.71−1.75 (overlapped, 2H), 2.65 (t, J = 5.7 Hz, 2H), 3.88 (t, J = 6.3 Hz, 2H), 6.72 (d, J = 9.0 Hz, 2H), 7.05 (d, J = 9.0 Hz, 2H), 7.14−7.22 (overlapped, 15H). 13C NMR (75 MHz, CDCl3, 298 K): δ 26.1, 26.8, 29.5, 33.5, 42.1, 64.5, 67.9, 113.4, 126.0, 127.6, 131.3, 132.3, 138.9, 147.3, 157.2. Anal. Calcd for C31H33NO: C, 85.48; H, 7.64; N, 3.22. Found: C, 85.50; H, 7.65; N, 3.23. Synthesis of Compound 19. Derivative 18 (0.25 g, 1.13 mmol) was added to a solution of derivative 17 (0.49 g, 1.13 mmol) in CHCl3 (8.0 mL). The mixture was stirred at room temperature for 2 h and then solvent was removed under reduced pressure to give the imine intermediate as yellow oil, which was used in the next step without further purification. A solution of the imine in CH3OH (15 mL) was cooled to 0 °C and then NaBH4 (0.85 g, 22.60 mmol) was slowly added. The mixture was allowed to warm to room temperature and stirred for 1 h. The solvent was removed under reduced pressure and the residue was partitioned between AcOEt (120 mL) and an aqueous saturated solution of NaHCO3 (100 mL). The organic layer was removed under reduced pressure. The resulting crude product was purified by flash chromatography on silica gel (CH2Cl2/CH3OH, 95/ 5, v/v) to give the amine derivative. The amine derivative (0.27 g, 0.42 mmol) was dissolved in THF (50 mL) at 0 °C and an aqueous solution of HCl (37% w/w, 0.50 mmol) was added dropwise. The mixture was allowed to warm to room temperature and was kept stirring for 1 h. The solvent was removed under reduced pressure to give a residue, which was dissolved in hot CH3CN. The solution was cooled at room temperature to give a white precipitate, which was collected by filtration and dried under vacuum to give derivative 19 as a white solid (0.21 g, 0.31 mmol, 74% compared to the amine intermediate). Mp: 110−115 °C. 1H NMR (300 MHz, CD3OD, 298 K): δ 1.41−1.54 (overlapped, 10H), 1.65−1.76 (overlapped, 6H), 2.96 (m, 2H), 3.51 (t, J = 6.4 Hz, 2H), 3.92 (m, 4H), 4.06 (s, 2H), 6.72 (d, J = 8.7 Hz, 2H), 6.92 (d, J = 8.4 Hz, 2H), 7.00 (d, J = 8.7 Hz, 2H), 7.10−7.20 (overlapped, 15H), 7.34 (d, J = 8.4 Hz, 2H). 13C NMR (75 MHz, CD3OD, 298 K): δ 27.0, 27.1, 27.3, 30.1, 30.3, 33.6, 48.2, 51.9, 62.9, 65.5, 68.6, 69.0, 114.3, 116.1, 124.2, 127.0, 128.4, 132.2, 132.5, 133.3, 140.2, 148.5, 158.6, 161.6. Anal. Calcd for C44H52ClNO3: C, 77.91; H, 7.73; N, 2.06. Found: C, 77. 90.; H, 7.74; N, 2.05. Synthesis of Derivative 8+·TFPB−. Sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (0.13 g, 0.15 mmol) was added to a solution of derivative 19 (0.10 g, 0.15 mmol) in dry CH3OH (30 mL). The mixture was kept stirring in the dark for 24 h and then the solvent was removed and deionized water was added, obtaining a precipitate that was filtered off and lyophilized overnight to give a yellowbrownish solid, derivative 8+·TFPB− (0.20 g, 0.13 mmol, 87%). Mp: >108 °C (dec); 1H NMR (300 MHz, CD3OD, 298 K): δ 1.47−1.54 (overlapped, 10H), 1.62−1.76 (overlapped, 6H), 2.96 (t, J = 7.5 Hz, 2H), 3.51 (t, J = 6.3 Hz, 2H), 3.82−3.96 (overlapped, 4H), 4.06 (s, 2H), 6.73 (d, J = 8.8 Hz, 2H), 6.93 (d, J = 8.6 Hz, 2H), 7.01 (d, J = 8.8 Hz, 2H), 7.10−7.21 (overlapped, 15H), 7.34 (d, J = 8.6 Hz, 2H), 7.55 (s, 12H). 13C NMR (75 MHz, CD3OD, 298 K): δ 26.7, 27.0, 27.1, 27.3, 30.1, 30.3, 30.7, 33.6, 51.9, 62.9, 65.6, 68.6, 69.1, 114.2, 116.1, 118.5, 120.4, 124.0, 124.2, 127.0, 127.6, 128.4, 130.3, 130.7, 131.2, 132.2, 132.4, 133.3, 135.8, 140.2, 148.4, 158.6, 161.9, 162.5, 163.2, 163.9. Anal. Calcd for C76H64BF24NO3: C, 60.61; H, 4.28; N, 0.93. Found: C, 60.66; H, 4.29; N, 0.95. Preparation of 20+·TFPB− and 21+·TFPB− Pseudorotaxanes for 1D and 2D NMR Studies. Derivative 3 (3.0 × 10−3 M) and thread 7+·TFPB− or 8+·TFPB− (3.0 × 10−3 M) were dissolved in

CDCl3. The mixture was stirred at 55 °C for 12 h and were used for 1D and 2D NMR studies. Synthesis of Oriented Calix[2]rotaxane 22+·TFPB−. Derivative 3 (0.20 g, 0.14 mmol) and thread 7+·TFPB− (0.21 g, 0.14 mmol) were dissolved in dry CHCl3 (15 mL). The mixture was stirred at 55 °C for 12 h and checked by 1H NMR, and the mixture was used for the subsequent stoppering reaction. Di-n-butyltindilaurate (3 drops) was added to the above mixture, and subsequently, 4-triphenylmethylphenylisocyanate (0.25 g, 0.70 mmol) was added. The reaction was kept stirring at 55 °C for 72 h and then the solvent was removed under reduced pressure. The resulting crude product was purified by column chromatography on silica gel (hexanes/CH2Cl2, 70/30, v/v) to give 22+·TFPB− [2]rotaxanes as a yellow pale oil (0.07 g, 0.02 mmol, 13%). 1 H NMR (600 MHz, CDCl3, 298 K): δ −0.76 to −0.71 (overlapped, β and γ, 4H), −0.51 (m, δ, 2H), 0.27 (m, α, 2H), 0.71 (m, ε, 2H), 0.90 (t, J = 7.1 Hz, 18H), 1.21 (s, 54H, But), 1.28−1.35 (overlapped, 36H,), 1.60−1.64 (overlapped, 4H), 1.72−1.76 (overlapped, 12H), 1.77−1.94 (overlapped, 4H), 3.21 (broad, 2H), 3.46 and 4.51* (AX, ArCH2Ar, J = 14.4 Hz, 12H), 3.47−4.58 (AX, J = 14.4 Hz 12H), 3.49 (t, ζ, J = 6.8 Hz, 2H), 3.78 (t, J = 8.0 Hz, 12H), 3.99−4.05 (overlapped, 4H), 4.28 and 4.94* (AX, ArH, J = 9.1 Hz, 12H), 5.68 (broad, 2H), 6.3 (broad, 2H), 6.80 (d, J = 8.9 Hz, 2H), 7.07−7.13 (overlapped, 4H), 7.20−7.28 (overlapped, 46H), 7.54 (s, 4H), 7.74 (s, 8H), 7.86 (d, J = 8.5 Hz, 2H). 13C NMR (150 MHz, CDCl3, 298 K): δ 14.2, 23.0, 25.7, 30.5, 31.6, 32.2, 34.4, 64.2, 64.5, 64.7, 67.8, 68.4, 75.8, 113.3, 113.4, 114.6, 117.6, 123.9, 125.7, 126.0,126.1, 126.2, 126.4, 126.5, 127.5, 127.6, 127.7, 127.8, 128.0, 128.5, 128.9, 129.1, 129.7, 131.0, 131.1, 131.3, 131.4, 132.0, 132.4, 132.5, 132.6, 135.0, 146.9, 147.0, 147.2, 152.0, 157.2, 161.0, 161.4, 161.7, 162.1. *Signals attributable to endo-benzyl22+·TFPB− stereoisomer. Anal. Calcd for C204H239BF24N2O10: C, 73.23; H, 7.20; N, 0.84. Found: C, 73.26; H, 7.25; N, 0.83. Synthesis of the Oriented Calix[2]rotaxane 23+·TFPB−. Derivative 3 (0.20 g, 0.14 mmol) and thread 7+·TFPB− (0.21 g, 0.14 mmol) or 8+·TFPB− (0.21 g, 0.14 mmol) were dissolved in dry CHCl3 (15 mL). The mixture was stirred at 55 °C for 12 h and checked by 1H NMR, and the mixture was used for the subsequent stoppering reaction. Di-n-butyltindilaurate (3 drops) was added to the above mixture, and subsequently 4-triphenylmethylphenylisocyanate (0.25 g, 0.70 mmol) was added. The reaction was kept stirring at 55 °C for 72 h and then the solvent was removed under reduced pressure. The resulting crude product was purified by column chromatography on silica gel (hexanes/CH2Cl2, 70/30, v/v) to give 23+·TFPB− [2]rotaxanes as a yellow pale oil (0.18 g, 0.05 mmol, 39%). endoAlkyl 23+cone·TFPB−: 1H NMR (600 MHz, CDCl3, 298 K): δ −0.72 (overlapped, β and γ, 4H,), −0.38 (broad, δ, 2H), 0.36 (broad, α, 2H), 0.81 (broad, ε, 2H), 0.96 (t, J = 6.5 Hz, 18H), 1.20 (s, 54H), 1.30− 1.38 (overlapped, 36H), 1.56−1.61 (overlapped, 4H), 1.78−1.79 (overlapped, 14H), 1.93−1.96 (m, 2H), 3.27 (m, 2H), 3.33 (t, ζ, J = 6.2 Hz, 2H), 3.48 and 4.55* (AX, ArCH2Ar, J = 12.2 Hz, 12H), 3.49 and 4.60 (AX, ArCH2Ar, J = 13.2 Hz, 12H), 3.80 (t, J = 7.7 Hz, 12H), 3.90* (t, OCH2calix, J = 6.1 Hz, 12H), 4.05 (t, J = 6.2 Hz, 2H), 4.16* (t, J = 6.1 Hz, 2H), 4.23 (t, J = 6.6 Hz, 2H), 4.25 and 4.91* (AX, ArH, J = 9.6 Hz, 4H), 4.27* (t, J = 7.2 Hz, 2H), 5.80 (broad, +NH2, 2H), 6.55 (d, J = 8.5 Hz, 2H), 6.60 (s, 1H), 7.09 (d, J = 8.2 Hz, 2H), 7.20−7.30 (overlapped, 48H), 7.56 (s, 4H), 7.76 (s, 8H), 7.89 (d, J = 8.2 Hz, 2H). 13C NMR (150 MHz, CDCl3, 298 K): δ 15.5, 24.2, 25.3, 25.6, 26.88, 26.94, 27.2, 27.4, 29.5, 30.4, 31.1, 31.7, 33.4, 35.7, 49.4, 53.9, 65.7, 65.9, 66.5, 67.8, 69.6, 77.1, 114.5, 115.8, 118.8, 118.8, 119.0, 123.3, 125.07, 125.10, 126.9, 127.3, 127.4, 127.7, 127.8, 128.7, 128.8, 128.9, 130.0, 130.17, 130.19, 130.20, 130.38, 130.40, 130.41, 130.6, 132.5, 133.3, 133.4, 133.8, 136.3, 137.1, 140.3, 143.4, 148.2, 148.5, 153.2, 155.1, 158.0, 162.2, 162.7, 163.0, 163.3, 163.6. Anal. Calcd for C204H239BF24N2O10: C, 73.23; H, 7.20; N, 0.84. Found: C, 73.22; H, 7.19; N, 0.85. *Signals attributable to the endo-benzyl-23+·TFPB− stereoisomer. 8981

DOI: 10.1021/acs.joc.7b01388 J. Org. Chem. 2017, 82, 8973−8983

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The Journal of Organic Chemistry

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Li, H. Chem. Commun. 2016, 52, 14416−14418. (d) Yeon, Y.; Leem, S.; Wagen, C.; Lynch, V. M.; Kim, S. K.; Sessler, J. L. Org. Lett. 2016, 18, 4396−4399. For applications in self-assembly processess, see the following: (e) Asfari, Z.; Böhmer, V.; Harrowfield, J.; Vicens, J. (Eds.) Calixarenes 2001; Kluwer, Dordrecht, 2001. For applications as catalysts, see the following:. (f) Homden, D. H.; Redshaw, C. Chem. Rev. 2008, 108, 5086−5130. (g) De Rosa, M.; Talotta, C.; Soriente, A. Lett. Org. Chem. 2009, 6, 301−305. (h) De Rosa, M.; Soriente, A.; Concilio, G.; Talotta, C.; Gaeta, C.; Neri, P. J. Org. Chem. 2015, 80, 7295−7300. (9) In calixarene chemistry, the term “inherent” is particularly used to indicate a novel form of chirality that “arises from the introduction of a curvature in an ideal planar structure that is devoid of perpendicular symmetry planes in its bidimensional representation”. See the following: Szumna, A. Chem. Soc. Rev. 2010, 39, 4274−4285. Thus, regarding the calix-wheel 3, we introduce the term “inherent directionality” to emphasize that its vaselike structure (a curvature with respect to its ideal planar structure) results in two structurally different rims (endo and exo). (10) (a) Arduini, A.; Orlandini, G.; Secchi, A.; Credi, A.; Silvi, S.; Venturi, M. In Calixarenes and Beyond; Neri, P., Sessler, J. L., Wang, M.-X., Eds.; Springer: Dordrecht, 2016; pp 761−781. (b) Arduini, A.; Bussolati, R.; Credi, A.; Secchi, A.; Silvi, S.; Semeraro, M.; Venturi, M. J. Am. Chem. Soc. 2013, 135, 9924−9930. (c) Arduini, A.; Calzavacca, F.; Pochini, A.; Secchi, A. Chem. - Eur. J. 2003, 9, 793−799. (d) Arduini, A.; Ciesa, F.; Fragassi, M.; Pochini, A.; Secchi, A. Angew. Chem., Int. Ed. 2005, 44, 278−281. (e) Arduini, A.; Credi, A.; Faimani, G.; Massera, C.; Pochini, A.; Secchi, A.; Semeraro, M.; Silvi, S.; Ugozzoli, F. Chem. - Eur. J. 2008, 14, 98−106. (f) Arduini, A.; Bussolati, R.; Credi, A.; Monaco, S.; Secchi, A.; Silvi, S.; Venturi, M. Chem. - Eur. J. 2012, 18, 16203−16213. (g) Zanichelli, V.; Ragazzon, G.; Arduini, A.; Credi, A.; Franchi, P.; Orlandini, G.; Venturi, M.; Lucarini, M.; Secchi, A.; Silvi, S. Eur. J. Org. Chem. 2016, 2016, 1033− 1042. (h) Orlandini, G.; Ragazzon, G.; Zanichelli, V.; Secchi, A.; Silvi, S.; Venturi, M.; Arduini, A.; Credi, A. Chem. Commun. 2017, 53, 6172−6174. (11) (a) Talotta, C.; Gaeta, C.; Neri, P. Org. Lett. 2012, 14, 3104− 3107. (b) Gaeta, C.; Talotta, C.; Mirra, S.; Margarucci, L.; Casapullo, A.; Neri, P. Org. Lett. 2013, 15, 116−119. For other examples of stereoisomerism based on threading of calixarene macrocycles, see the following: (c) Gaeta, C.; Talotta, C.; Neri, P. Chem. Commun. 2014, 50, 9917−9920. (d) Talotta, C.; De Simone, N. A.; Gaeta, C.; Neri, P. Org. Lett. 2015, 17, 1006−1009. (e) De Rosa, M.; Talotta, C.; Gaeta, C.; Soriente, A.; Neri, P.; Pappalardo, S.; Gattuso, G.; Notti, A.; Parisi, M. F.; Pisagatti, I. J. Org. Chem. 2017, 82, 5162−5168. (12) (a) Ciao, R.; Talotta, C.; Gaeta, C.; Margarucci, L.; Casapullo, A.; Neri, P. Org. Lett. 2013, 15, 5694−5697. (b) Ciao, R.; Talotta, C.; Gaeta, C.; Neri, P. Supramol. Chem. 2014, 26, 569−578. (13) TFPB = tetrakis[3,5-bis(trifluoromethyl)phenyl]borate, a superweak anion; see the following: (a) Strauss, S. H. Chem. Rev. 1993, 93, 927−942. (b) Gaeta, C.; Talotta, C.; Farina, F.; Teixeira, F. A.; Marcos, P. A.; Ascenso, J. R.; Neri, P. J. Org. Chem. 2012, 77, 10285−10293. (c) Gaeta, C.; Talotta, C.; Farina, F.; Camalli, M.; Campi, G.; Neri, P. Chem. - Eur. J. 2012, 18, 1219−1230. (d) Talotta, C.; Gaeta, C.; Neri, P. J. Org. Chem. 2014, 79, 9842−9846. (e) Hou, H.; Leung, K. C.-F.; Lanari, D.; Nelson, A.; Stoddart, J. F.; Grubbs, R. H. J. Am. Chem. Soc. 2006, 128, 15358−15359. (f) For a review on counterion effects in supramolecular chemistry, see the following: Gasa, T. B.; Valente, C.; Stoddart, J. F. Chem. Soc. Rev. 2011, 40, 57− 78. (g) Talotta, C.; Gaeta, C.; De Rosa, M.; Ascenso, J. R.; Marcos, P. M.; Neri, P. Eur. J. Org. Chem. 2016, 2016, 158−167. (14) Hirose, K. In Analytical Methods in Supramolecular Chemistry; Schalley, C. A., Ed.; Wiley-VCH: Weinheim, Germany, 2007; Chapter 2, pp 17−54. (15) Grimme, S. J. Comput. Chem. 2006, 27, 1787−1799 The Grimme’s dispersion correction has been already used for DFT calculations in calixarene-based pseudorotaxane structures; see ref 11.. (16) See the Supporting Information for further details.

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b01388. 1 H and 13C NMR spectra, 2D NMR spectra of new compounds, and details on the DFT calculations (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected] ORCID

Carmen Talotta: 0000-0002-2142-6305 Carmine Gaeta: 0000-0002-2160-8977 Margherita De Rosa: 0000-0001-7451-5523 Placido Neri: 0000-0003-4319-1727 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We thank the Italian MIUR (PRIN 20109Z2XRJ_006) for financial support and the Centro di Tecnologie Integrate per la Salute (Project PONa3_00138), Università di Salerno, for time on the the 600 MHz NMR instrument.

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REFERENCES

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DOI: 10.1021/acs.joc.7b01388 J. Org. Chem. 2017, 82, 8973−8983

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The Journal of Organic Chemistry (17) These values are in accord with the C−H···π distance parameters indicated by Nishio: Suezawa, H.; Ishihara, S.; Umezawa, Y.; Tsuboyama, S.; Nishio, M. Eur. J. Org. Chem. 2004, 2004, 4816− 4822. (18) Previously our group reported an example of ammonium-based pseudorotaxane, in which the calix-wheel 3 adopted a 1,2,3-alternate conformation; see ref 11. (19) Pfammatter, M. J.; Siljegovic, V.; Darbre, T.; Keese, R. Helv. Chim. Acta 2001, 84, 678−689.

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DOI: 10.1021/acs.joc.7b01388 J. Org. Chem. 2017, 82, 8973−8983