Synthesis and Structure of Feet-to-Feet Connected Bisresorcinarenes

Nov 17, 2017 - Bisresorcinarenes 1a–d were obtained in excellent yields, and 1e was finally obtained in 50% yield. X-ray diffraction analysis showed...
0 downloads 0 Views 3MB Size
Article pubs.acs.org/joc

Cite This: J. Org. Chem. 2017, 82, 13220−13230

Synthesis and Structure of Feet-to-Feet Connected Bisresorcinarenes Daisuke Shimoyama, Toshiaki Ikeda, Ryo Sekiya, and Takeharu Haino* Department of Chemistry, Graduate School of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima 739-8526, Japan S Supporting Information *

ABSTRACT: Bisresorcinarenes 1a−d were obtained in excellent yields, and 1e was finally obtained in 50% yield. X-ray diffraction analysis showed that 1a and 1b adopted helical conformations, whereas the two resorcinarenes of 1c−e were in parallel orientations in which the clefts of the aliphatic chains entrapped one or two solvent molecules. The conformational study revealed that the helix interconversion between the (P)- and (M)-helical conformers depended on the length of the aliphatic chains. 1a had the largest energetic barrier to helix interconversion, while in 1b, its more flexible aliphatic chains lowered its energetic barriers. The P/M interconversion of 1a was coupled with the clockwise/ anticlockwise interconversion of the interannular hydrogen bonding of the two resorcinarenes. The large negative entropic contributions indicate that the transition state is most likely more ordered than the ground states, suggesting that the transition state is most likely symmetric and is solvated by water molecules. Calculations at the M06-2X/6-31G(d,p) level revealed that the more stable (P)-conformation has clockwise interannular hydrogen bonding between the two resorcinarenes.



INTRODUCTION Ditopic hosts possessing two guest binding sites that are conformationally coupled are extensively utilized in the development of elaborated supramolecular systems with positive or negative cooperativity. 1 In their molecular recognition, the binding of the first guest induces a conformational change in the hosts, which influences the binding of the second guest. This cooperative regulation offers promising applications in artificial allosteric systems,2 ion-pair recognition,3 supramolecular polymerization,4 etc. Developing ditopic hosts showing cooperative regulation requires molecular scaffolds that can easily be chemically functionalized to produce the desired guest binding sites. Crown ethers,5 calixarenes,6 calixpyrroles,7 pillararenes,8 resorcinarenes,9 and other compounds10 are often employed to construct homo- and heteroditopic hosts due to their synthetic versatility and the tunability of guest binding. During the course of our studies on calixarene chemistry,11 we recently introduced bisresorcinarenes 1a−d, which are composed of two resorcinarenes connected with four aliphatic chains in a feet-to-feet fashion (Figure 1), as a versatile scaffolds for homoditopic hosts.12 The intermolecular rim-to-rim hydrogen bonding of 1a−d produced hydrogen bonded supramolecular polymers. The upper-rim functionalization of 1a and 1c with phosphonate groups produced phosphonatebridged biscavitands, which demonstrate allosteric regulation in ammonium guest binding.13 1a−d were synthesized through multicomponent condensation reactions with eight resorcinol molecules and four flexible dialdehydes molecules; however, this reaction suffered from extremely poor chemical yields. Bis(dimethoxy acetals) were developed to be latent alternatives © 2017 American Chemical Society

Figure 1. Structure of bisresorcinarenes 1a−e.

to the dialdehydes, but the product yields remained moderate. Therefore, an improvement in the reaction conditions was highly important. Herein, we report the improved syntheses of 1a−e and their structures in solution and in the solid state. The chemical yields of 1a−d were more than 76%, and 1e was finally obtained in 50% yield. X-ray diffraction analysis of 1a−e confirmed the feetto-feet-connected bisresorcinarene structures, in which 1a and 1b adopted the helical conformations, while the two resorcinarene units of 1c−e showed parallel orientations. The longer alkyl chains of 1c−e produced additional guest binding sites where solvent molecules were accommodated. The shortest aliphatic chains of 1a increased the barrier of the P/ M helix interconversion to 53 kJ mol −1 . The P/M Received: September 12, 2017 Published: November 17, 2017 13220

DOI: 10.1021/acs.joc.7b02301 J. Org. Chem. 2017, 82, 13220−13230

Article

The Journal of Organic Chemistry interconversion of 1a was correlated with flipping between clockwise/anticlockwise interannular hydrogen bonding of the resorcinarene units. The most stable conformation of 1a was determined to be the clockwise−(P)-helicity−clockwise conformation using density functional theory (DFT) calculations.

improve the yields of the bisresorcinarenes, and differences in solvent properties are unlikely to influence the product yields. The alkyl chains lengths significantly influenced the chemical yields of the bisresorcinarenes. Bisresorcinarenes 1a−d were obtained in good yields, ranging from 97 to 76% (entry 9, 27, 45, and 63), but the yield of 1e dropped significantly to approximately 50% (entry 74). However, a bisresorcinarene possessing alkyl chains longer than 14 carbons has not yet been obtained, and this might be the limit of these reaction conditions. There are two plausible reaction pathways; one is that an oxonium intermediate directly reacts with resorcinol, and the other is that an acyclic bisacetal, formed through the transacetalization of a cyclic acetal with the solvent alcohols, reacts with resorcinol (Scheme 2). To determine the main pathway of the macrocyclization reactions, 1,1,10,10-tetrakispropyloxydecane was subjected to the reaction in n-propanol instead of 4c, which resulted in a significant reduction in the yield of 1c from 97% to 61% yield. Therefore, the oxonium ion of the cyclic acetal most likely reacts with resorcinol, and the transacetalization process might be negligible. A cyclic acetal is commonly in equilibrium with its open oxonium ion in acidic alcohols. At high temperatures, the equilibrium is pushed toward the entropically favored open form, which can accelerate the macrocyclization reaction. Accordingly, the macrocyclization requires high temperatures to obtain the bisresorcinarenes. Crystal Structures of Bisresorcinarenes. Colorless, X-ray quality single crystals of 1b−d were grown from DMF or dimethylacetamide (DMA) solutions of 1b−d by slow diffusion of ethyl acetate, diethyl ether, and benzene for 1b, 1c, and 1d, respectively, at room temperature. The single crystals of 1e were obtained from a DMF solution after standing in the solution for a few days. The single crystals of 1b−e were subjected to X-ray diffraction analysis at −150 °C.17 1b crystallized in the monoclinic crystal system with the space group P21/c (#14). The unit cell contained four molecules of 1b; however, only one of the molecules was crystallographically independent. 1c formed a triclinic crystal system with the space group P−1 (#2). Two molecules of 1c existed in the unit cell and are related to each other through an inversion center. 1d and 1e formed monoclinic crystal systems with the space group P21/n (#14) and P21/c (#14). The unit cell contained only two molecules of 1d or 1e, and the halves of the molecules were crystallographically independent. The crystallographic parameters are summarized in Table S1. Figure 2 illustrates the side and top views of the X-ray crystal structures of 1a−e. The steric requirement of the aliphatic chains influenced the relative orientations of the two resorcinarenes. 1a and 1b adopted helical structures with twist angles of 32.0° and 28.4° between the two resorcinarenes, respectively, whereas two resorcinarene units of 1c adopted an eclipsed conformation with the twisted angle of 2.2°, and slipped parallel orientations of the two resorcinarene units were found in 1d and in 1e. Solvent molecules, DMF and DMA, were located within all the resorcinarene cavities (Figure 2). One of the nitrogenconnected methyl groups of the solvents was pointed inside the cavities of 1a−e, generating the effective CH/π interactions without any assistance from O−H···OC hydrogen bonding between the carbonyl group of the solvent molecule and the hydroxyl group of the resorcinarene unit. There were additional guest binding spaces in 1c−e. The aliphatic chains of 1c



RESULTS AND DISCUSSION Synthesis of Bisresorcinarene. Dialdehydes 2a−d, bisdimethoxyacetals 3a−e, bisdioxolans 4a−e, bisdioxanes 5a−e, bisdimethyldioxanes 6a−e, and bistetramethyldioxolanes 7a−d were used to find reaction conditions suitable for macrocyclizations with resorcinol (Scheme 1, Table 1). Cram Scheme 1. Acid-Catalyzed Macrocyclization

and co-workers reported a condensation reaction for the preparation of a resorcinarene in ethanol in the presence of hydrochloric acid.14 These reaction conditions were first applied to the macrocyclization of dialdehydes 2a−d with resorcinol.15 The desired bisresorcinarenes 1a−d were obtained in poor yields of less than 29% (entry 2, 20, 38, and 56). Small dialdehydes are generally very reactive in acidic conditions; intra- and intermolecular aldol reactions might be favored and compete with the formation of the bisresorcinarenes. To prevent competitive undesired side reactions, dialdehydes 2a−d were converted to the bisacetals; in particular, cyclic derivatives 4−7 are quite stable even in acidic alcohols for a certain period.16 Acyclic bis(dimethoxy acetals) 3a−d were subjected to the macrocyclization conditions with resorcinol in ethanol to give 1a−d in moderate yields (entry 5, 23, 41, and 59). Employing cyclic bisacetals 4a−d and 5a−d greatly improved the product yields (entry 8, 26, 29, 44, 47, and 62), whereas substituted bisacetals 6a−d and 7a−d did not. Therefore, the unsubstituted bisdioxolan and bisdioxane structures were found to show a certain reactivity for the macrocyclization. Solvents can influence the reaction outcomes. The macrocyclization reactions were studied in methanol, ethanol, and npropanol under refluxing conditions. The reactions in npropanol gave remarkably improved the yields; bisresorcinarenes 1a−c were obtained in quantitative yields (entry 9, 27, and 45). The reaction temperatures can impact the product yields as well; therefore, n-propanol was used for the reaction of 4c at four different temperatures (Table 2). The product yields were directly correlated with the reaction temperatures. When the reaction temperature was lowered to 25 °C, the product yield dropped to 5%. Thus, high temperatures are most likely 13221

DOI: 10.1021/acs.joc.7b02301 J. Org. Chem. 2017, 82, 13220−13230

Article

The Journal of Organic Chemistry Table 1. Synthesis of Bisresorcinarenes 1a−d

a

entry

R−(CH2)n−R

solvent

product

yield (%)

entry

R−(CH2)n−R

solvent

product

yield (%)

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

2a

MeOH EtOH PrOH MeOH EtOH PrOH MeOH EtOH PrOH MeOH EtOH PrOH MeOH EtOH PrOH MeOH EtOH PrOH MeOH EtOH PrOH MeOH EtOH PrOH MeOH EtOH PrOH MeOH EtOH PrOH MeOH EtOH PrOH MeOH EtOH PrOH

1a

11c 11c 7c 13c 45a 12c 29c 55b 81b 19c 33c 70b 31c 30c 18c 17c 20c 18c 11b 27a 20b 40b 62a 70b 67b 84b 97b 49b 75b 84b 30b 69b 79b 30c 34c 23c

37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76

2c

MeOH EtOH PrOH MeOH EtOH PrOH MeOH EtOH PrOH MeOH EtOH PrOH MeOH EtOH PrOH MeOH EtOH PrOH MeOH EtOH PrOH MeOH EtOH PrOH MeOH EtOH PrOH MeOH EtOH PrOH MeOH EtOH PrOH MeOH EtOH PrOH PrOH

1c

26b 19a 29b 36b 57a 49b 32b 72b 97b 41b 76b 87b 46b 59b 81b 20c 29c 14c NDc 29a NDc 4c 33a 2c 36c 59b 76b 38c 33b 53b 12c 55b 76b 6c 3c 11c 36b 50b 42b 35b

3a

4a

5a

6a

7a

2b

3b

4b

5b

6b

7b

1b

4c

5c

6c

7c

2d

3d

4d

5d

6d

7d

3e 4e 5e 6e

1d

1e

Ref 12. bIsolated yield. cNo precipitation due to low yield. Yield was determined by 1H NMR using p-nitrobenzyl alcohol as an internal standard.

Table 2. Synthesis of 1c in n-Propanol at Different Temperatures

a

3c

Scheme 2. Two Reaction Pathways of the Macrocyclization

entry

R−(CH2)8−R

T/°C

product

yield (%)a

1 2 3 4

4c 4c 4c 4c

80 60 40 25

1c 1c 1c 1c

74 42 15 5

The yield of 1c was determined by 1H NMR.

adopted a ring-like structure with an empty space that entrapped a DMA molecule (Figure 3). 1d and 1e forced two solvent molecules inside the binding space formed among the aliphatic chains. The oxygen atoms of the solvent molecules were close to the lower aromatic C−H protons with the shortest C−H···O distances being 2.959(5) Å, 2.610(6) Å, and 2.828(6) Å for 1c, 1d, and 1e, respectively.18 The aromatic C− H bonds directed at the guest oxygen atom most likely generate

somewhat weak attractions, resulting in host−guest complexation among the aliphatic chains. Conformational Behaviors of Bisresorcinarenes. In the solid state, 1a and 1b adopted helical conformations that can dynamically isomerize in solution. Figure 4 illustrates two 13222

DOI: 10.1021/acs.joc.7b02301 J. Org. Chem. 2017, 82, 13220−13230

Article

The Journal of Organic Chemistry

Figure 2. Side and top views of X-ray crystal structures of (a) 1a,12 (b) 1b, (c) 1c, (d) 1d, and (e) 1e. In (a) and (b), only (P)-conformers are shown. Color scheme: gray (carbon), red (oxygen), blue (nitrogen). The hydrogen atoms are omitted for clarity except on entrapped solvents.

Figure 4. Schematic representation of (a) clockwise/anticlockwise interconversion of the interannular hydrogen bonds, and (b) P/M interconversion of the helical conformations.

Figure 3. Intercalation of the solvent molecules among the four aliphatic chains of (a, b) 1c and (c, d) 1d. In (a), the guest was disordered over the three sites. Only the guest molecule with the highest site occupancy factor is shown for clarity. Color scheme of the guests is as follows: gray (carbon), blue (nitrogen), and red (oxygen).

suggesting the strengthening of the 8-membered interannular hydrogen bonding of the resorcinarene units. The phenolic hydroxyl groups of 1a only coalesced at Tc ≈ − 10 °C. At lower temperatures, two separate O−H signals appeared, corresponding to an interannular hydrogen-bonded hydroxyl group and a free, non-hydrogen-bonded hydroxyl group (Figure 4a). Therefore, the energetic barrier (ΔG‡) of the clockwise/ anticlockwise interconversion is 53.6 kJ mol−1 (Figure 5a).19 At low temperatures, the methylene protons Hb and Hc both eventually split into two signals, appearing at 1.63 and 3.02 ppm and at 1.28 and 1.48 ppm, respectively, which reduce the D4 symmetry of 1a. The peak divergence suggests that the P/M interconversion of the helical conformations becomes slow on the NMR time scale below −30 °C with an energetic barrier of 53.1 kJ mol−1 at Tc ≈ − 6 °C. The sizable energetic barrier of

unique stereoisomers of the helical conformations; one is the clockwise/anticlockwise interannular hydrogen bonding of the resorcinarene unit (Figure 4a), and the other is the (P)- and (M)- helical conformations of the bisresorcinarene (Figure 4b). To study the conformational behaviors of 1a and 1b in solution, variable temperature 1H NMR measurements were carried out in DMF-d7 (Figure 5). The phenolic hydroxyl protons and the methylene protons of 1a−e appeared to be singlets at 60 °C, which is indicative of the D4h conformation, in which a rapid exchange between the clockwise and anticlockwise hydrogen bonding arrays occurred. Cooling the solution led to the downfield shift of the phenolic hydroxyl groups, 13223

DOI: 10.1021/acs.joc.7b02301 J. Org. Chem. 2017, 82, 13220−13230

Article

The Journal of Organic Chemistry

Figure 5. Variable temperature 1H NMR spectra (500 MHz) of (a) 1a and (b) 1b in DMF-d7.

Figure 6. Two exchange mechanisms for the phenolic hydrogens of 1a.

Table 3. Rate Constants and Activation Parameters Ha

Hc

a

T/°C

k/s−1

ΔH‡/kJ mol−1

ΔS‡/J K−1 mol−1

ΔG‡/kJ mol−1

ΔG‡/kJ mol−1a

−40 −45 −50 −55 −40 −45 −50 −55

4.67 3.94 3.52 3.00 3.45 2.96 2.58 2.20

10.3

−186

53.6

10.7

−187

53.7 52.7 51.8 50.9 54.3 53.4 52.4 51.5

53.1

Determined at coalescence temperatures.

the P/M interconversion process was coincident with that of the clockwise/anticlockwise interconversion process of the interannular hydrogen bonding. In contrast, 1b−e did not show any signal splitting below −50 °C; therefore, a certain amount of flexibility in the alkyl chains reduces the energetic barriers to the interconversions. (Figure 5b). To find signal pairs that exchange slowly on the NMR time scale, ROESY spectra were acquired at −50 °C. Significant ROE cross peaks were observed between the phenolic hydroxyl

groups and residual water molecules in the NMR solvents, indicating that the water molecules were hydrogen-bonded to the phenolic hydroxyl groups. The positive signs of the ROE signals surprisingly ruled out the chemical exchange between the phenolic hydrogens and the water protons.20 In contrast, negative ROEs between two split phenolic hydrogens were observed, indicating that the two phenolic hydrogens were intramolecularly exchanging with each other even though water molecules were hydrogen bonded. Figure 6 shows two potential 13224

DOI: 10.1021/acs.joc.7b02301 J. Org. Chem. 2017, 82, 13220−13230

Article

The Journal of Organic Chemistry

conformers, CPC, CPA, and APA, were optimized with the Gaussian 09 program at the M06-2X/6-31G(d,p) level of theory.23 The CPC conformer was found to be the most stable followed by the CPA and APA conformations (Figure 7).

mechanisms for the exchange between the two phenolic hydrogens: one is the “relay mechanism” in which the hydrogen-bonded water molecule participates in a concerted six-membered transition state, and the other is the “stepwise mechanism.” The proton exchange between the hydrogenbonded water molecule and the phenolic hydrogens is involved in the “relay mechanism,” which is certainly not the case here due to the positive ROE correlation. Therefore, the exchange between the two phenolic hydrogens most likely follows the intramolecular “stepwise mechanism.” To establish the correlation between the interconversion of the clockwise/anticlockwise interannular hydrogen bonding and the P/M interconversion of the helical conformations, EXSY experiments were used to determine the exchange rate constants using NOESY pulse sequences.21 The rate constant of 3.52 s−1 for the clockwise/anticlockwise interconversion was close to that of 2.58 s−1 for the P/M interconversion at −50 °C, implying that the clockwise/anticlockwise interconversion of the interannular hydrogen bonding is likely coupled with the P/ M interconversion (Figure 4). These conformational changes show the strong temperature dependence of the rate constants and the activation free energies (Table 3). To obtain a detailed picture of these interconversion processes, enthalpic (ΔH‡) and entropic (ΔS‡) contributions to the free energy of activation were obtained by an Eyring plot (Table 3). The large negative contribution by entropy to the activation should mean that the transition states must be more ordered than the ground states since they are involved in both the interconversion processes. During the P/M interconversion process, the transition state most likely has higher structural symmetry and lower molecular flexibility than the ground state conformations, which explains the negative contribution of entropy. The transition state of the “stepwise mechanism” for the clockwise/anticlockwise interconversion most likely breaks the interannular hydrogen bonds, producing free hydrogenbonding sites, which are bridged with the hydrogen-bonded water molecule. Therefore, more water molecules can solvate the transition state with the tetrahedrally-coordinated water molecule, which has more acidic OH protons than the trigonal water molecule of the ground state (Figure S60). This solvation also results in the negative contribution in entropy and partly compensates for the unfavorable enthalpic contribution in the distorted transition state structure. Moreover, the enthalpic and entropic contributions of the clockwise/anticlockwise interconversion completely matched those of the P/M interconversion, confirming that the two processes are coupled with each other. Accordingly, the helical nature of the bisresorcinarene conformation determines the direction of the cyclic interannular hydrogen bonds. To find the most stable structure of 1a, a conformational search of 1a was carried out using MacroModel ver. 9.1 software using low-mode search with the MMFFs force field.22 The 1000 possible initial geometries of 1a that were generated were subsequently optimized to give three major conformers within 12 kJ mol−1 of each other. One is a clockwise−(P)helicity−clockwise conformation (CPC) adopting the two resorcinarenes with the clockwise interannular hydrogen bond array, another is a clockwise−(P)-helicity−anticlockwise conformation (CPA) with the resorcinarenes with the clockwise and the anticlockwise interannular hydrogen bond arrays, and the other is an anticlockwise−(P)-helicity−anticlockwise conformation (APA) possessing the two resorcinarenes with the anticlockwise interannular hydrogen bond arrays. The three

Figure 7. Energy-minimized structures of (a) CPC, (b) CPA, and (c) APA for 1a.

Although the difference in energy from the most stable conformer was approximately 0.6 kJ mol−1, CPC was confirmed to be the most stable conformation, and it is most likely to be the dominant form in solution.



CONCLUSIONS In conclusion, we have optimized the reaction conditions to produce bisresorcinarenes 1a−d in excellent yields. Bisdioxolans were found to be the best reagents for the macrocyclization. The reactions rely on the reactivity of the bisfunctionalized aliphatic chains, which prevent undesired side reactions. X-ray diffraction analysis of 1a−e revealed that 1a and 1b adopted the helical conformations, whereas the long aliphatic chains of 1c−e preferred parallel orientations for their two resorcinarene units, and small organic molecules were entrapped within the cavities among the long alkyl chains. The conformational study revealed that the helix interconversion between the (P)- and (M)-helical conformers depended on the length of the aliphatic chains. 1a has the largest energy barrier to helix interconversion, and the energy barriers in 1b−e were lower due to their flexible alkyl chains. The interconversion between the clockwise/anticlockwise interannular hydrogen bonding of the resorcinarenes was found to be coupled with the helix interconversion. The large negative entropic contributions indicate that the transition states should be more ordered than the ground states, suggesting that the transition state is most likely symmetric and is solvated with water molecules. The conformational analysis and the density functional theory calculations of 1a suggested that the (P)-helical conformer prefers the clockwise an interannular hydrogen bond array (CPC). Therefore, the helix interconversion of 1a occurs between CPC and its enantiomer. 13225

DOI: 10.1021/acs.joc.7b02301 J. Org. Chem. 2017, 82, 13220−13230

Article

The Journal of Organic Chemistry



was dried over sodium sulfate, and the solvent was removed in vacuo. The crude product was purified by column chromatography (silica gel, hexane/ethyl acetate) and recrystallized from hexane to give 5b as a white solid (28.4 g, 79%). Mp 45−47 °C; 1H NMR (300 MHz, chloroform-d1): δ 4.49 (t, 2H, J = 5.2 Hz), 4.09 (dd, 4H, J = 10.6, 5.2 Hz), 3.74 (dt, 4H, J = 10.6, 2.6 Hz), 2.06 (m, 2H), 1.56 (m, 4H), 1.22−1.44 (m, 10H) ppm; 13C NMR (75 MHz, chloroform-d1): δ 102.4, 66.9, 35.2, 29.3, 25.9, 23.9 ppm; IR (ATR): ν 2929, 2855, 1469, 1374, 1236, 1135 cm−1; HRMS (ESI-Orbitrap) m/z: [M+H]+ calcd for C14H27O4 259.1904; found 259.1903; Anal. Calcd for C14H26O4: C 65.09, H 10.14, found C 64.99, H 10.14. 1,6-Bis(5,5-dimethyl-1,3-dioxan-2-yl)hexane (6b). A mixture of 1,1,8,8-tetramethoxyoctane (17.6 g, 75.1 mmol), 2,2-dimethyl-1,3propanediol (107 g, 1.03 mol), and pyridinium p-toluenesulfonate (28.2 g, 112 mmol) in distilled dichloromethane (190 mL) was stirred at room temperature. After stirred for 15 h, the mixture was neutralized to pH 7−8 with sodium hydrogen carbonate and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and the solvent was removed in vacuo. The crude product was purified by column chromatography (silica gel, hexane/ethyl acetate) and recrystallized from hexane to give 6b as a white solid (19.6 g, 83%). Mp 61−63 °C; 1H NMR (300 MHz, chloroform-d1): δ 4.39 (t, 2H, J = 5.2 Hz), 3.57 (d, 4H, J = 10.4 Hz), 3.42 (d, 4H, J = 10.4 Hz), 1.60 (m, 4H), 1.24−1.46 (m, 8H), 1.18 (s, 6H), 0.71 (s, 6H) ppm; 13C NMR (75 MHz, chloroform-d1): δ 102.3, 77.2, 34.9, 30.2, 29.4, 23.9, 23.0, 21.9 ppm; IR (ATR): ν 2947, 2922, 2850, 1474, 1396, 1122, 1078 cm−1; HRMS (ESI-Orbitrap) m/z: [M+NH4]+ calcd for C18H38NO4 332.2795; found 332.2795; Anal. Calcd for C18H34O4: C 68.75, H 10.90, found C 68.87, H 10.79. 1,6-Bis(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)hexane (7b). A mixture of 1,1,8,8-tetramethoxyoctane (32.8 g, 140 mmol), pinacol (50.0 g, 423 mmol), and pyridinium p-toluenesulfonate (22.0 g, 87.5 mmol) in distilled dichloromethane (300 mL) was stirred at room temperature. After stirred for 15 h, the mixture was neutralized to pH 7−8 with sodium hydrogen carbonate and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and the solvent was removed in vacuo. The crude product was purified by column chromatography (silica gel, hexane/ethyl acetate) and recrystallized from hexane to give 7b as a white solid (12.2 g, 25%). Mp 37−38 °C; 1H NMR (300 MHz, chloroform-d1): δ 5.01 (t, 2H, J = 5.2 Hz), 1.56 (m, 4H), 1.27−1.46 (m, 8H), 1.19 (s, 24H) ppm; 13 C NMR (75 MHz, chloroform-d1): δ 100.9, 81.5, 36.4, 29.5, 24.4, 24.2, 22.1 ppm.; IR (ATR): ν 2974, 2924, 2851, 1219, 1165, 1133 cm−1; HRMS (ESI-Orbitrap) m/z: [M+NH4]+ calcd for C20H42NO4 360.3108; found 360.3108; Anal. Calcd for C20H38O4: C 70.13, H 11.18, found C 70.13, H 11.18. 1,6-Bis(1,3-dioxolan-2-yl)octane (4c). A mixture of 1,1,10,10tetramethoxydecane (7.50 g, 28.6 mmol), ethylene glycol (30 mL, 538 mmol), and pyridinium p-toluenesulfonate (6.15 g, 24.5 mmol) in distilled dichloromethane (70 mL) was stirred at room temperature. After stirred for 15 h, the mixture was neutralized to pH 7−8 with sodium hydrogen carbonate and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and the solvent was removed in vacuo. The crude product was purified by column chromatography (silica gel, hexane/ethyl acetate) and recrystallized from hexane to give 4c as a white solid (5.16 g, 70%). Mp 47−49 °C; 1H NMR (300 MHz, chloroform-d1): δ 4.84 (t, 2H, J = 5.2 Hz), 3.90 (AA’BB’, 8H), 1.60 (m, 4H), 1.24−1.47 (m, 12H) ppm; 13C NMR (75 MHz, chloroform-d1): δ 104.7, 64.8, 33.9, 29.5, 29.4, 24.1 ppm; IR (ATR): ν 2943, 2920, 2890, 2853, 1470, 1161, 1123, 1040 cm−1; HRMS (ESI-Orbitrap) m/z: [M+H]+ calcd for C14H27O4 259.1904; found 259.1903; Anal. Calcd for C14H26O4: C 65.09, H 10.14, found C 65.23, H 9.97. 1,8-Bis(1,3-dioxan-2-yl)octane (5c). A mixture of 1,1,10,10tetramethoxydecane (36.1 g, 138 mmol), 1,3-propanediol (140 mL, 1.95 mol), and pyridinium p-toluenesulfonate (51.2 g, 204 mmol) in distilled dichloromethane (337 mL) was stirred at room temperature. After stirred for 15 h, the mixture was neutralized to pH 7−8 with sodium hydrogen carbonate and extracted with ethyl acetate. The

EXPERIMENTAL SECTION

General. All reagents and solvents were of the commercial reagent grade and were used without further purification except where noted. 1 H and 13C NMR spectra were recorded at 25 °C, and chemical shifts were reported as parts per million (ppm) relative to chloroform (chloroform-d1, δ = 7.26 ppm for 1H and 77.0 ppm for 13C), dimethylformamide (DMF-d7, δ = 8.03 ppm for 1H and 163.2 ppm for 13 C), acetone (acetone-d6, δ = 2.05 ppm for 1H), and DMSO (DMSOd6, δ = 2.50 ppm for 1H). Preparative separations were performed by silica gel gravity column chromatography (Silica Gel 60N (spherical, neutral)). 1,4-Bis(5,5-dimethyl-1,3-dioxan-2-yl)butane (6a). A mixture of 1,1,6,6-tetramethoxyhexane (6.16 g, 29.9 mmol), 2,2-dimethyl-1,3propanediol (43.0 g, 413 mmol), and pyridinium p-toluenesulfonate (11.2 g, 44.6 mmol) in distilled dichloromethane (74 mL) was stirred at room temperature. After stirred for 15 h, the mixture was neutralized to pH 7−8 with sodium hydrogen carbonate and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and the solvent was removed in vacuo. The crude product was purified by column chromatography (silica gel, hexane/ethyl acetate) and recrystallized from hexane to give 6a as a white solid (7.45 g, 87%). Mp 75−77 °C; 1H NMR (300 MHz, chloroform-d1): δ 4.40 (t, 2H, J = 5.0 Hz), 3.59 (d, 4H, J = 11.2 Hz), 3.40 (d, 4H, J = 11.2 Hz), 1.62 (m, 4H), 1.42 (m, 4H), 1.18 (s, 6H), 0.71 (s, 6H) ppm; 13C NMR (75 MHz, chloroform-d1): δ 102.1, 77.2, 34.8, 30.2, 23.9, 23.0, 21.9 ppm; IR (ATR): ν 2950, 2929, 2844, 1470, 1396, 1121, 1080 cm−1; HRMS (ESI-Orbitrap) m/z: [M+H]+ calcd for C16H31O4 287.2217; found 287.2219; Anal. Calcd for C16H30O4: C 67.10, H 10.56, found C 66.85, H 10.32. 1,4-Bis(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)butane (7a). A mixture of 1,1,6,6-tetramethoxyhexane (5.30 g, 25.7 mmol), pinacol (9.30 g, 78.7 mmol), and pyridinium p-toluenesulfonate (4.00 g, 15.9 mmol) in distilled dichloromethane (55 mL) was stirred at room temperature. After stirred for 15 h, the mixture was neutralized to pH 7−8 with sodium hydrogen carbonate and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and the solvent was removed in vacuo. The crude product was purified by column chromatography (silica gel, hexane/ethyl acetate) and recrystallized from hexane to give 7a as a white solid (4.53 g, 56%). Mp 42−43 °C; 1H NMR (300 MHz, chloroform-d1): δ 5.02 (t, 2H, J = 5.1 Hz), 1.58 (m, 4H), 1.43 (m, 4H), 1.19 (s, 24H) ppm; 13C NMR (75 MHz, chloroform-d1): δ 100.8, 81.6, 36.4, 24.6, 24.2, 22.1 ppm; IR (ATR): ν 2973, 2919, 2860, 1220, 1156, 1132 cm−1; HRMS (ESI-Orbitrap) m/z: [M+H]+ calcd for C18H35O4 315.2530; found 315.2537; Anal. Calcd for C18H34O4: C 68.75, H 10.90, found C 68.66, H 10.83. 1,6-Bis(1,3-dioxolan-2-yl)hexane (4b). A mixture of 1,1,8,8tetramethoxyoctane (32.5 g, 139 mmol), ethylene glycol (143 mL, 2.56 mol), and pyridinium p-toluenesulfonate (30.0 g, 119 mmol) in distilled dichloromethane (200 mL) was stirred at room temperature. After stirred for 15 h, the mixture was neutralized to pH 7−8 with sodium hydrogen carbonate and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and the solvent was removed in vacuo. The crude product was purified by column chromatography (silica gel, hexane/ethyl acetate) and recrystallized from hexane to give 4b as a white solid (25.6 g, 80%). Mp 35−36 °C; 1H NMR (300 MHz, chloroform-d1): δ 4.83 (t, 2H, J = 4.8 Hz), 3.89 (AA’BB’, 8H), 1.64 (m, 4H), 1.28−1.48 (m, 8H) ppm; 13C NMR (75 MHz, chloroform-d1): δ 104.6, 64.8, 33.8, 29.4, 23.9 ppm; IR (ATR): ν 2942, 2920, 2888, 2856, 1470 1163, 1122 cm−1; HRMS (ESI-Orbitrap) m/z: [M+Na]+: calcd for C12H22O4Na 253.1410; found 253.1411; Anal. Calcd for C12H22O4: C 62.58, H 9.63, found C 62.74, H 9.83. 1,6-Bis(1,3-dioxan-2-yl)hexane (5b). A mixture of 1,1,8,8-tetramethoxyoctane (32.5 g, 139 mmol), 1,3-propanediol (140 mL, 1.95 mol), and pyridinium p-toluenesulfonate (30.0 g, 119 mmol) in distilled dichloromethane (200 mL) was stirred at room temperature. After stirred for 15 h, the mixture was neutralized to pH 7−8 with sodium hydrogen carbonate and extracted with ethyl acetate. The organic layer 13226

DOI: 10.1021/acs.joc.7b02301 J. Org. Chem. 2017, 82, 13220−13230

Article

The Journal of Organic Chemistry organic layer was dried over sodium sulfate, and the solvent was removed in vacuo. The crude product was purified by column chromatography (silica gel, hexane/ethyl acetate) and recrystallized from hexane to give 5c as a white solid (28.8 g, 73%). Mp 55−57 °C; 1H NMR (300 MHz, chloroform-d1): δ 4.49 (t, 2H, J = 5.2 Hz), 4.10 (dd, 4H, J = 10.9, 4.9 Hz), 3.75 (dt, 4H, J = 10.9, 2.4 Hz), 2.07 (m, 2H), 1.56 (m, 4H), 1.21−1.43 (m, 14H) ppm; 13C NMR (75 MHz, chloroform-d1): δ 102.5, 66.9, 35.2, 29.4, 25.9, 24.0 ppm; IR (ATR): ν 2929, 2852, 1470, 1372, 1233, 1138 cm−1; HRMS (ESI-Orbitrap) m/z: [M+H]+ calcd for C16H31O4 287.2217; found 287.2217; Anal. Calcd for C16H30O4: C 67.10, H 10.56, found C 67.14, H 10.45. 1,8-Bis(5,5-dimethyl-1,3-dioxan-2-yl)octane (6c). A mixture of 1,1,10,10-tetramethoxydecane (1.98 g, 7.55 mmol), 2,2-dimethyl-1,3propanediol (11.0 g, 106 mmol), and pyridinium p-toluenesulfonate (2.90 g, 11.5 mmol) in distilled dichloromethane (30 mL) was stirred at room temperature. After stirred for 15 h, the mixture was neutralized to pH 7−8 with sodium hydrogen carbonate and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and the solvent was removed in vacuo. The crude product was purified by column chromatography (silica gel, hexane/ethyl acetate) and recrystallized from hexane to give 6c as a white solid (2.22 g, 86%). Mp 57−58 °C; 1H NMR (300 MHz, chloroform-d1): δ 4.39 (t, 2H, J = 5.1 Hz), 3.59 (d, 4H, J = 11.4 Hz), 3.41 (d, 4H, J = 11.4 Hz), 1.60 (m, 4H), 1.22−1.46 (m, 12H), 1.18 (s, 6H), 0.71 (s, 6H) ppm; 13C NMR (75 MHz, chloroform-d1): δ 102.3, 77.2, 34.9, 30.2, 29.4, 24.0, 23.0, 21.9 ppm; IR (ATR): ν 2949, 2921, 2851, 1469, 1389, 1123, 1081 cm−1; HRMS (ESI-Orbitrap) m/z: [M+H]+ calcd for C20H39O4 343.2843; found 343.2844; Anal. Calcd for C20H38O4: C 70.13, H 11.18, found C 70.22, H 11.18. 1,8-Bis(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)octane (7c). A mixture of 1,1,10,10-tetramethoxydecane (2.02 g, 7.70 mmol), pinacol (12.7 g, 107 mmol), and pyridinium p-toluenesulfonate (2.90 g, 11.5 mmol) in distilled dichloromethane (30 mL) was stirred at room temperature. After stirred for 15 h, the mixture was neutralized to pH 7−8 with sodium hydrogen carbonate and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and the solvent was removed in vacuo. The crude product was purified by column chromatography (silica gel, hexane/ethyl acetate) to give 7c as colorless liquid (1.28 g, 45%). 1 H NMR (300 MHz, chloroform-d1): δ 5.02 (t, 2H, J = 5.1 Hz), 1.55 (m, 4H), 1.23−1.44 (m, 12H), 1.19 (s, 24H) ppm; 13C NMR (75 MHz, chloroform-d1): δ 100.9, 81.5, 36.4, 29.6, 29.4, 24.4, 24.2, 22.0 ppm; IR (ATR): ν 2974, 2925, 2856, 1219, 1157, 1129 cm−1; HRMS (ESI-Orbitrap) m/z: [M + Na]+ calcd for C22H42O4Na 393.2975; found 393.2976. 1,1,10,10-Tetrapropoxydecane. A mixture of 1,1,10,10-tetramethoxydecane (5.95 g, 22.7 mmol) and pyridinium p-toluenesulfonate (8.62 g, 34.3 mmol) in n-propanol (100 mL) was stirred at 110 °C. After stirred for 15 h, the mixture was neutralized to pH 7−8 with sodium hydrogen carbonate and extracted with diethyl ether. The organic layer was dried over sodium sulfate, and the solvent was removed in vacuo. The crude product was purified by column chromatography (silica gel, hexane/ethyl acetate) to give the desired product as colorless liquid (5.94 g, 70%). 1 H NMR (300 MHz, chloroform-d1): δ 4.46 (t, 2H, J = 5.9 Hz), 3.46 (AA’BB’, 8H), 1.60 (m, 4H), 1.59 (sext., 8H, J = 7.4 Hz), 1.22− 1.42 (m, 12H), 0.93 (t, 12H, J = 7.4 Hz) ppm; 13C NMR (75 MHz, chloroform-d1): δ 103.1, 67.1, 33.5, 29.5, 24.8, 23.1, 10.8 ppm; IR (ATR): ν 2926, 2876, 2856, 1465, 1377, 1352, 1125, 1067 cm−1; HRMS (ESI-Orbitrap) m/z: [M+Na]+ calcd for C22H46O4Na 397.3288 found 397.3292. 1,10-Bis(1,3-dioxolan-2-yl)decane (4d). A mixture of 1,1,12,12tetramethoxydodecane (39.8 g, 137 mmol), ethylene glycol (143 mL, 2.56 mol), and pyridinium p-toluenesulfonate (30.0 g, 119 mmol) in distilled dichloromethane (200 mL) was stirred at room temperature. After stirred for 15 h, the mixture was neutralized to pH 7−8 with sodium hydrogen carbonate and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and the solvent was removed in vacuo. The crude product was purified by column

chromatography (silica gel, hexane/ethyl acetate) and recrystallized from hexane to give 4d as a white solid (27.9 g, 71%). Mp 52−53 °C; 1H NMR (300 MHz, chloroform-d1): δ 4.84 (t, 2H, J = 4.9 Hz), 3.90 (AA’BB’, 8H), 1.64 (m, 4H), 1.22−1.47 (m, 16H) ppm; 13C NMR (75 MHz, chloroform-d1): δ 104.7, 64.8, 33.9, 29.5 × 2, 24.1 ppm; IR (ATR): ν 2943, 2918, 2851, 1471, 1159, 1122, 1049 cm−1; HRMS (ESI-Orbitrap) m/z: [M+H]+ calcd for C16H31O4 287.2217; found 287.2218; Anal. Calcd for C16H30O4: C 67.10, H 10.56, found C 66.91, H 10.51. 1,10-Bis(1,3-dioxan-2-yl)decane (5d). A mixture of 1,1,12,12tetramethoxydodecane (31.7 g, 109 mmol), 1,3-propanediol (146 mL, 2.04 mol), and pyridinium p-toluenesulfonate (24.0 g, 95.5 mmol) in distilled dichloromethane (160 mL) was stirred at room temperature. After stirred for 15 h, the mixture was neutralized to pH 7−8 with sodium hydrogen carbonate and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and the solvent was removed in vacuo. The crude product was purified by column chromatography (silica gel, hexane/ethyl acetate) and recrystallized from hexane to give 5d as a white solid (21.9 g, 64%). Mp 64−66 °C; 1H NMR (300 MHz, chloroform-d1): δ 4.50 (t, 2H, J = 5.2 Hz), 4.10 (dd, 4H, J = 11.5, 5.0 Hz), 3.75 (dt, 4H, J = 11.5, 2.2 Hz), 2.07 (m, 2H), 1.56 (m, 4H), 1.20−1.43 (m, 18H) ppm; 13C NMR (75 MHz, chloroform-d1): δ 102.5, 66.9, 35.2, 29.5, 25.9, 24.0 ppm; IR (ATR): ν 2922, 2853, 1471, 1372, 1234, 1136 cm−1; HRMS (ESI-Orbitrap) m/z: [M+Na]+ calcd for C18H34O4Na 337.2349; found 337.2351; Anal. Calcd for C18H34O4: C 68.75, H 10.90, found C 68.88, H 10.84. 1,10-Bis(5,5-dimethyl-1,3-dioxan-2-yl)decane (6d). A mixture of 1,1,12,12-tetramethoxydodecane (25.8 g, 88.8 mmol), 2,2-dimethyl1,3-propanediol (127 g, 1.22 mol), and pyridinium p-toluenesulfonate (29.2 g, 116 mmol) in distilled dichloromethane (220 mL) was stirred at room temperature. After stirred for 15 h, the mixture was neutralized to pH 7−8 with sodium hydrogen carbonate and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and the solvent was removed in vacuo. The crude product was purified by column chromatography (silica gel, hexane/ethyl acetate) and recrystallized from hexane to give 6d as a white solid (26.3 g, 80%). Mp 64−65 °C; 1H NMR (300 MHz, chloroform-d1): δ 4.40 (t, 2H, J = 5.1 Hz), 3.59 (d, 4H, J = 11.2 Hz), 3.41 (d, 4H, J = 11.2 Hz), 1.61 (m, 4H), 1.21−1.47 (m, 16H), 1.18 (s, 6H), 0.71 (s, 6H) ppm; 13C NMR (75 MHz, chloroform-d1): δ 102.3, 77.2, 34.9, 30.2, 29.5, 24.0, 23.0, 21.9 ppm; IR (ATR): ν 2948, 2921, 2850, 1469, 1389, 1121, 1082 cm−1; HRMS (ESI-Orbitrap) m/z: [M+NH4]+ calcd for C22H46NO4 388.3421; found 388.3424; Anal. Calcd for C22H42O4: C 71.31, H 11.42, found C 71.34, H 11.47. 1,10-Bis(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)decane (7d). A mixture of 1,1,12,12-tetramethoxydodecane (27.0 g, 92.9 mmol), pinacol (61.0 g, 516 mmol), and pyridinium p-toluenesulfonate (30.0 g, 119 mmol) in distilled dichloromethane (230 mL) was stirred at room temperature. After stirred for 15 h, the mixture was neutralized to pH 7−8 with sodium hydrogen carbonate and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and the solvent was removed in vacuo. The crude product was purified by column chromatography (silica gel, hexane/ethyl acetate) to give 7d as colorless liquid (15.5 g, 42%). 1 H NMR (300 MHz, chloroform-d1): δ 5.02 (t, 2H, J = 5.0 Hz), 1.56 (m, 4H), 1.21−1.45 (m, 16H), 1.19 (s, 24H) ppm; 13C NMR (75 MHz, chloroform-d1): δ 101.0, 81.5, 36.5, 29.6, 29.5, 24.5, 24.2, 22.1 ppm; IR (ATR): ν 2976, 2923, 2855, 1219, 1156, 1129 cm−1; HRMS (ESI-Orbitrap) m/z: [M+NH4]+ calcd for C24H50NO4 416.3728; found 416.3734. 1,12-Bis(1,3-dioxolan-2-yl)dodecane (4e). A mixture of 1,1,14,14tetramethoxytetradecane (3.00 g, 9.42 mmol), ethylene glycol (9.4 mL, 169 mmol), and pyridinium p-toluenesulfonate (3.60 g, 14.3 mmol) in distilled dichloromethane (23 mL) was stirred at room temperature. After stirred for 12 h, the mixture was neutralized to pH 7−8 with sodium hydrogen carbonate and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and the solvent was removed in vacuo. The crude product was purified by column 13227

DOI: 10.1021/acs.joc.7b02301 J. Org. Chem. 2017, 82, 13220−13230

Article

The Journal of Organic Chemistry

(CH2) ppm; IR (ATR): ν 3298, 2927, 2856, 1617, 1501, 1436 cm−1; HRMS (ESI-Orbitrap) m/z: [M+H]+ calcd for C80H89O16 1305.6145, found 1305.6155; Anal. Calcd for C80H88O16·4.5H2O: C 69.30, H 7.05, found C 69.54, H 7.34. Bisresorcinarene 1c. A mixture of resorcinol (0.700 g, 6.36 mmol) and 1,8-bis(1,3-dioxolan-2-yl)octane (4c) (0.415 g, 1.61 mmol) in npropanol (1.9 mL) was stirred for 3 days at 100 °C in the presence of conc. HCl (0.51 mL). After the reaction mixture was concentrated in vacuo, the crude product was washed with water several times to give 1c as a pale yellow solid (0.555 g, 97%). Mp > 300 °C; 1H NMR (500 MHz, DMF-d7, 60 °C): δ 9.21 (s, 16H), 7.47 (s, 8H), 6.35 (s, 8H), 4.34 (t, 8H, J = 7.6 Hz), 2.34 (m, 16H), 1.45 (m, 32H), 1.34 (m, 16H) ppm; 13C NMR (125 MHz, DMF-d7, 60 °C): δ 153.1 (C), 125.3 (C), 124.7 (CH), 104.1 (CH), 35.5 (CH2), 35.3 (CH), 31.5 (CH2), 31.3 (CH2), 30.0 (CH2) ppm; IR (ATR): ν 3303, 2923, 2852, 1611, 1503, 1435 cm−1; HRMS (ESI-Orbitrap) m/z: [M+H]+ calcd for C88H105O16 1417.7410, found 1417.7397; Anal. Calcd for C88H104O16·6H2O: C 69.27, H 7.66, found C 69.33, H 7.46. Bisresorcinarene 1d. A mixture of resorcinol (0.700 g, 6.36 mmol) and 1,10-bis(1,3-dioxolan-2-yl)decane (4d) (0.458 g, 1.60 mmol) in npropanol (1.9 mL) was stirred for 3 days at 80 °C in the presence of conc. HCl (0.51 mL). After the reaction mixture was concentrated in vacuo, the crude product was washed with water several times to give 1d as a pale yellow solid (0.466 g, 76%). Mp > 300 °C; 1H NMR (500 MHz, DMF-d7, 60 °C): δ 9.20 (s, 16H), 7.45 (s, 8H), 6.34 (s, 8H), 4.33 (t, 8H, J = 7.8 Hz), 2.31 (m, 16H), 1.26−1.52 (m, 64H) ppm; 13 C NMR (125 MHz, DMF-d7, 60 °C): δ 153.2 (C), 125.4 (C), 124.9 (CH), 104.2 (CH), 35.4 (CH2), 35.2 (CH), 31.7 (CH2), 31.6 (CH2), 31.3 (CH2), 30.0 (CH2) ppm; IR (ATR): ν 3306, 2920, 2849, 1618, 1502, 1436 cm−1; HRMS (ESI-Orbitrap) m/z: [M+H]+ calcd for C96H121O16 1529.8649, found 1529.8667; Anal. Calcd for C96H120O16· 5H2O: C 71.45, H 8.39, found C 71.17, H 8.09. Bisresorcinarene 1e. A mixture of resorcinol (0.700 g, 6.36 mmol) and 1,12-bis(1,3-dioxolan-2-yl)dodecane (4e) (0.504 g, 1.60 mmol) in n-propanol (1.9 mL) was stirred for 3 days at 100 °C in the presence of conc. HCl (0.51 mL). After the reaction mixture was concentrated in vacuo, the crude product was washed with water and acetone several times to give 1e as a pale yellow solid (0.332 g, 50%). Mp > 300 °C; 1 H NMR (500 MHz, DMF-d7, 60 °C): δ 9.17 (s, 16H), 7.56 (s, 8H), 6.33 (s, 8H), 4.31 (t, 8H, J = 7.8 Hz), 2.33 (m, 16H), 1.25−1.50 (m, 80H) ppm; 13C NMR (125 MHz, DMF-d7, 60 °C): δ 153.0 (C), 125.4 (C), 125.3 (CH), 104.0 (CH), 35.3 (CH), 35.2 (CH2), 31.7 (CH2), 31.6 (CH2), 31.4 (CH2), 31.2 (CH2), 29.9 (CH2) ppm; IR (ATR): ν 3318, 2919, 2850, 1616, 1502, 1437 cm−1; HRMS (ESI-Orbitrap) m/ z: [M+ H + Na]2+ calcd for C104H137O16Na 832.4897, found 832.4901; Anal. Calcd for C104H136O16: C 76.06, H 8.35, found C 75.68, H 8.29. X-ray Crystallography. X-ray quality single crystals of 1b−e were grown from DMF, DMA, and DMSO solutions by slow evaporation of benzene, ethyl acetate, and ether at room temperature. X-ray crystallographic data were collected on a Bruker SMART AEPX II ULTRA CCD diffractometer using graphite-monochromatized Mo− Kα radiation (λ = 0.71073 Å) at 123 K. The crystal structures were solved by the direct method using the SHELXS-2013 program and refined by successive differential Fourier syntheses and full-matrix least-squares procedures using the SHELXL-2013 program. Anisotropic thermal factors were applied to all non-hydrogen atoms. The hydrogen atoms were generated geometrically. Diffuse electron densities arising from the disordered solvents in 1b−e were treated with the SQUEEZE routine in the PLATON program. Crystallographic parameters are listed in Table S1 of the Supporting Information. CCDC 89014512 (1a), 1569094 (1b), 1569095 (1c), 1569096 (1d), 1569097 (1e (DMF)), and 1569098 (1e (DMSO)) contain the supplementary crystallographic data for this paper. These data are provided free of charge by The Cambridge Crystallographic Data Centre. Conformational Analysis. The conformational analyses of 1a−e were carried out with 1H NMR spectroscopy. DMF-d7 and acetone-d6 were used as solvents. The temperature range of DMF-d7 was +80 ∼ − 50 °C, and the range of acetone-d6 was +40 ∼ − 80 °C. The spectra were recorded every 10 °C. The barrier to the conformational change

chromatography (silica gel, hexane/ethyl acetate) and recrystallized from hexane to give 4e as a white solid (2.07 g, 70%). Mp 63−65 °C; 1H NMR (300 MHz, chloroform-d1): δ 4.84 (t, 2H, J = 5.0 Hz), 3.91 (AA’BB’, 8H), 1.64 (m, 4H), 1.20−1.48 (m, 20H); 13 C NMR (75 MHz, chloroform-d1): δ 104.7, 64.8, 33.9, 29.6 × 2, 29.5, 24.1 ppm; IR (ATR): ν 2943, 2915, 2890, 2849, 1471, 1157, 1122, 1039 cm−1; HRMS (ESI-Orbitrap) m/z: [M+H]+ calcd for C18H35O4 315.2530; found 315.2531; Anal. Calcd for C18H34O4: C 68.75, H 10.90, found C 68.51, H 10.88. 1,12-Bis(1,3-dioxan-2-yl)dodecane (5e). A mixture of 1,1,14,14tetramethoxytetradecane (3.00 g, 9.42 mmol), 1,3-propanediol (9.60 mL, 134 mmol), and pyridinium p-toluenesulfonate (3.60 g, 14.3 mmol) in distilled dichloromethane (23 mL) was stirred at room temperature. After stirred for 15 h, the mixture was neutralized to pH 7−8 with sodium hydrogen carbonate and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and the solvent was removed in vacuo. The crude product was purified by column chromatography (silica gel, hexane/ethyl acetate) and recrystallized from hexane to give 5e as a white solid (2.13 g, 66%). Mp 71−72 °C; 1H NMR (300 MHz, chloroform-d1): δ 4.50 (t, 2H, J = 5.1 Hz), 4.10 (dd, 4H, J = 10.9, 5.0 Hz), 3.76 (dt, 4H, J = 10.9, 2.3 Hz), 2.07 (m, 2H), 1.57 (m, 4H), 1.20−1.44 (m, 22H) ppm; 13C NMR (75 MHz, chloroform-d1): δ 102.5, 66.9, 35.3, 29.6, 29.5 × 2, 25.9, 24.0 ppm; IR (ATR): ν 2921, 2853, 1471, 1373, 1231, 1139 cm−1; HRMS (ESI-Orbitrap) m/z: [M+H]+ calcd for C20H39O4 343.2843; found 343.2843; Anal. Calcd for C20H38O4: C 70.13, H 11.18, found C 70.32, H 11.01. 1,12-Bis(5,5-dimethyl-1,3-dioxan-2-yl)dodecane (6e). A mixture of 1,1,14,14-tetramethoxytetradecane (5.67 g, 17.8 mmol), 2,2dimethyl-1,3-propanediol (25.4 g, 244 mmol), and pyridinium ptoluenesulfonate (6.70 g, 26.7 mmol) in distilled dichloromethane (45 mL) was stirred at room temperature. After stirred for 15 h, the mixture was neutralized to pH 7−8 with sodium hydrogen carbonate and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and the solvent was removed in vacuo. The crude product was purified by column chromatography (silica gel, hexane/ ethyl acetate) and recrystallized from hexane to give 6e as a white solid (5.96 g, 84%). Mp 70−71 °C; 1H NMR (300 MHz, chloroform-d1): δ 4.40 (t, 2H, J = 5.2 Hz), 3.60 (d, 4H, J = 10.8 Hz), 3.42 (d, 4H, J = 10.8 Hz), 1.62 (m, 4H), 1.20−1.45 (m, 20H), 1.19 (s, 6H), 0.72 (s, 6H) ppm; 13C NMR (75 MHz, chloroform-d1): δ 102.3, 77.2, 34.9, 30.2, 29.6 × 2, 24.0, 23.0, 21.9 ppm; IR (ATR): ν 2947, 2920, 2849, 1469, 1389, 1123, 1087 cm−1; HRMS (ESI-Orbitrap) m/z: [M+H]+ calcd for C24H47O4 399.3469; found 399.3469; Anal. Calcd for C24H46O4: C 72.31, H 11.63, found C 72.31, H 11.98. Bisresorcinarene 1a. A mixture of resorcinol (0.700 g, 6.36 mmol) and 1,4-bis(1,3-dioxolan-2-yl)butane (4a) (0.324 g, 1.60 mmol) in npropanol (1.9 mL) was stirred for 3 days at 100 °C in the presence of conc. HCl (0.51 mL). After the reaction mixture was concentrated in vacuo, the crude product was washed with ether and the precipitate was filtered to give 1a as a pale yellow solid (0.385 g, 81%). Mp > 300 °C; 1H NMR (500 MHz, DMF-d7, 60 °C): δ 9.33 (s, 16H), 7.49 (s, 8H), 6.39 (s, 8H), 4.39 (t, 8H, J = 7.5 Hz), 2.44 (m, 16H), 1.47 (m, 16H) ppm; 13C NMR (125 MHz, DMF-d7, 60 °C): δ 153.3 (C), 125.4 (C), 123.7 (CH), 104.6 (CH), 35.5 (CH), 34.4 (CH2), 29.2 (CH2) ppm; IR (ATR): ν 3262, 2924, 286 0, 1617, 1496, 1440 cm−1; HRMS (ESI-Orbitrap) m/z: [M+H]+ calcd for C72H73O16 1193.4893, found 1193.4899; Anal. Calcd for C72H72O16·5H2O: C 67.38, H 6.44, found C 67.42, H 6.35. Bisresorcinarene 1b. A mixture of resorcinol (0.700 g, 6.36 mmol) and 1,6-bis(1,3-dioxolan-2-yl)hexane (4b) (0.368 g, 1.60 mmol) in npropanol (1.9 mL) was stirred for 3 days at 100 °C in the presence of conc. HCl (0.51 mL). After the reaction mixture was concentrated in vacuo, the crude product was washed with water several times to give 1b as a pale yellow solid (0.505 g, 97%). Mp > 300 °C; 1H NMR (500 MHz, DMF-d7, 60 °C): δ 9.27 (s, 16H), 7.34 (s, 8H), 6.37 (s, 8H), 4.36 (t, 8H, J = 7.8 Hz), 2.30 (m, 16H), 1.57 (m, 16H), 1.39 (m, 16H) ppm; 13C NMR (125 MHz, DMF-d7, 60 °C): δ 153.2(C) 125.0 (C), 124.0 (CH), 104.3 (CH), 35.2 (CH2), 35.0 (CH), 31.0 (CH2), 30.0 13228

DOI: 10.1021/acs.joc.7b02301 J. Org. Chem. 2017, 82, 13220−13230

Article

The Journal of Organic Chemistry of the aliphatic methylenes (ΔG‡) of 1a was determined by the coalescence temperature (Tc) and the chemical shifts (δν) measured in the frozen structures. The δν values of the aliphatic methylenes of 1a were measured at Tc = −6 °C. ΔG‡ was calculated according to eq 1.

ΔG‡ = 8.314Tc[22.96 + ln(Tc/δν)]

2013, 3, 41−57. (e) Blanco, V.; Leigh, D. A.; Marcos, V. Chem. Soc. Rev. 2015, 44, 5341−5370. (f) Vlatković, M.; Collins, B. S. L.; Feringa, B. L. Chem. - Eur. J. 2016, 22, 17080−17111. (3) (a) Kim, S. K.; Sessler, J. L. Chem. Soc. Rev. 2010, 39, 3784−3809. (b) Gasa, T. B.; Valente, C.; Stoddart, J. F. Chem. Soc. Rev. 2011, 40, 57−78. (c) McConnell, A. J.; Beer, P. D. Angew. Chem., Int. Ed. 2012, 51, 5052−5061. (4) (a) Brunsveld, L.; Folmer, B. J. B.; Meijer, E. W.; Sijbesma, R. P. Chem. Rev. 2001, 101, 4071−4097. (b) Yagi, S.; Hyodo, Y.; Hirose, M.; Nakazumi, H.; Sakurai, Y.; Ajayaghosh, A. Org. Lett. 2007, 9, 1999− 2002. (c) Veling, N.; Thomassen, P. J.; Thordarson, P.; Elemans, J. A. A. W.; Nolte, R. J. M.; Rowan, A. E. Tetrahedron 2008, 64, 8535−8542. (d) Yagai, S.; Kitamura, A. Chem. Soc. Rev. 2008, 37, 1520−1529. (e) Danjo, H.; Hirata, K.; Noda, M.; Uchiyama, S.; Fukui, K.; Kawahata, M.; Azumaya, I.; Yamaguchi, K.; Miyazawa, T. J. Am. Chem. Soc. 2010, 132, 15556−15558. (f) Park, J. S.; Yoon, K. Y.; Kim, D. S.; Lynch, V. M.; Bielawski, C. W.; Johnston, K. P.; Sessler, J. L. Proc. Natl. Acad. Sci. U. S. A. 2011, 108, 20913−20917. (g) Haino, T. Polym. J. 2013, 45, 363−383. (5) (a) Rebek, J., Jr.; Costello, T.; Marshall, L.; Wattley, R.; Gadwood, R. C.; Onan, K. J. Am. Chem. Soc. 1985, 107, 7481−7487. (b) Shinkai, S.; Yoshida, T.; Manabe, O.; Fuchita, Y. J. Chem. Soc., Perkin Trans. 1 1988, 1431−1437. (c) Beer, P. D.; Stokes, S. E. Polyhedron 1995, 14, 2631−2635. (d) Yamaguchi, N.; Gibson, H. W. Chem. Commun. 1999, 789−790. (6) (a) Rudkevich, D. M.; Verboom, W.; Reinhoudt, D. N. J. Org. Chem. 1994, 59, 3683−3686. (b) Nagasaki, T.; Fujishima, H.; Takeuchi, M.; Shinkai, S. J. Chem. Soc., Perkin Trans. 1 1995, 1883− 1888. (c) Haino, T.; Katsutani, Y.; Akii, H.; Fukazawa, Y. Tetrahedron Lett. 1998, 39, 8133−8136. (d) Budka, J.; Lhoták, P.; Stibor, I.; Michlová, V.; Sykora, J.; Cisarová, I. Tetrahedron Lett. 2002, 43, 2857− 2861. (e) Garozzo, D.; Gattuso, G.; Notti, A.; Pappalardo, A.; Pappalardo, S.; Parisi, M. F.; Perez, M.; Pisagatti, I. Angew. Chem., Int. Ed. 2005, 44, 4892−4896. (f) Nabeshima, T.; Saiki, T.; Iwabuchi, J.; Akine, S. J. Am. Chem. Soc. 2005, 127, 5507−5511. (7) (a) Sessler, J. L.; Kim, S. K.; Gross, D. E.; Lee, C.-H.; Kim, J. S.; Lynch, V. M. J. Am. Chem. Soc. 2008, 130, 13162−13166. (b) Kim, S. K.; Sessler, J. L. Acc. Chem. Res. 2014, 47, 2525−2536. (c) OsorioPlanes, L.; Espelt, M.; Pericàs, M. A.; Ballester, P. Chem. Sci. 2014, 5, 4260−4264. (d) Romero, J. R.; Aragay, G.; Ballester, P. Chem. Sci. 2017, 8, 491−498. (8) (a) Li, C.; Han, K.; Li, J.; Zhang, H.; Ma, J.; Shu, X.; Chen, Z.; Weng, L.; Jia, X. Org. Lett. 2012, 14, 42−45. (b) Ogoshi, T.; Yoshikoshi, K.; Aoki, T.; Yamagishi, T. Chem. Commun. 2013, 49, 8785−8787. (c) Sun, N.; Xiao, X.; Liu, C.; Chen, C.; Jiang, J. RSC Adv. 2015, 5, 43218−43224. (9) (a) Atwood, J. L.; Szumna, A. J. Am. Chem. Soc. 2002, 124, 10646−10647. (b) Barrett, E. S.; Irwin, J. L.; Turner, P.; Sherburn, M. S. Org. Lett. 2002, 4, 1455−1458. (c) Ihm, H.; Ahn, J.-S.; Lah, M. S.; Ko, Y. H.; Paek, K. Org. Lett. 2004, 6, 3893−3896. (d) Staats, H.; Eggers, F.; Haß, O.; Fahrenkrug, F.; Matthey, J.; Lüning, U.; Lützen, A. Eur. J. Org. Chem. 2009, 2009, 4777−4792. (e) Durola, F.; Rebek, J., Jr. Angew. Chem., Int. Ed. 2010, 49, 3189−3191. (f) Tancini, F.; Gottschalk, T.; Schweizer, W. B.; Diederich, F.; Dalcanale, E. Chem. - Eur. J. 2010, 16, 7813−7819. (10) (a) Takeuchi, M.; Imada, T.; Shinkai, S. Angew. Chem., Int. Ed. 1998, 37, 2096−2099. (b) Chang, S.-Y.; Jang, H.-Y.; Jeong, K.-S. Chem. - Eur. J. 2004, 10, 4358−4366. (c) Kawai, H.; Katoono, R.; Nishimura, K.; Matsuda, S.; Fujiwara, K.; Tsuji, T.; Suzuki, T. J. Am. Chem. Soc. 2004, 126, 5034−5035. (d) Perraud, O.; Robert, V.; Martinez, A.; Dutasta, J.-P. Chem. - Eur. J. 2011, 17, 4177−4182. (11) (a) Haino, T.; Fukunaga, C.; Fukazawa, Y. Org. Lett. 2006, 8, 3545−3548. (b) Haino, T.; Kobayashi, M.; Fukazawa, Y. Chem. - Eur. J. 2006, 12, 3310−3319. (c) Hirao, T.; Tosaka, M.; Yamago, S.; Haino, T. Chem. - Eur. J. 2014, 20, 16138−16146. (d) Tsunoda, Y.; Fukuta, K.; Imamura, T.; Sekiya, R.; Furuyama, T.; Kobayashi, N.; Haino, T. Angew. Chem., Int. Ed. 2014, 53, 7243−7247. (12) Yamada, H.; Ikeda, T.; Mizuta, T.; Haino, T. Org. Lett. 2012, 14, 4510−4513.

(1)

The exchange rate (k) between the enantiomeric conformations of 1a under the given temperature was determined using the EXSYcalc program. Computational Methods. The conformational analyses of 1a−e were carried out using Macromolecule Ver. 9.0 with the MMFFs force field. The energy-minimized structures of the three stable conformers of CPC, CPA, and APA for 1a were obtained by the Gaussian 09 program using the M06-2X/6-31G(d,p) basis set. The Cartesian coordinates of the three conformers are compiled in the Supporting Information.



ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b02301. 1 H and 13C NMR spectra of all new synthesized compounds; VT NMR and X-ray crystallographic data for 1a−e; computational details of DFT calculations, ROESY spectra, and NOESY spectra for 1a; and Eyring plot and activation parameters for the P/M and the clockwise/anticlockwise interconversions of 1a (PDF) X-ray crystallographic data for compounds 1b, 1c, 1d, 1e (DMF), and 1e (DMSO) (CIF)



AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]; Fax: +81-82-424-0724; Tel: +81-82-424-7427 ORCID

Takeharu Haino: 0000-0002-0945-2893 Notes

The authors declare no competing financial interest.



ACKNOWLEDGMENTS This work was supported by Grants-in-Aid for Scientific Research, JSPS KAKENHI Grant Numbers JP15H03817 and JP15KT0145, and by Grants-in-Aid for Scientific Research on Innovative Areas, JSPS KAKENHI Grant Numbers JP15H00946 (Stimuli-responsive Chemical Species), JP15H00752 (New Polymeric Materials Based on ElementBlocks), JP17H05375 (Coordination Asymmetry), and JP17H05159 (π-Figuration). We also acknowledge Iketani Science and Technology Foundation.



REFERENCES

(1) (a) Rebek, J., Jr. Acc. Chem. Res. 1984, 17, 258−264. (b) Beer, P. D. Chem. Soc. Rev. 1989, 18, 409−450. (c) Shinkai, S.; Ikeda, M.; Sugasaki, A.; Takeuchi, M. Acc. Chem. Res. 2001, 34, 494−503. (d) Takeuchi, M.; Ikeda, M.; Sugasaki, A.; Shinkai, S. Acc. Chem. Res. 2001, 34, 865−873. (e) Kay, E. R.; Leigh, D. A.; Zerbetto, F. Angew. Chem., Int. Ed. 2007, 46, 72−191. (f) Nabeshima, T.; Akine, S. Chem. Rec. 2008, 8, 240−251. (g) Hunter, C. A.; Anderson, H. L. Angew. Chem., Int. Ed. 2009, 48, 7488−7499. (h) Kremer, C.; Lützen, A. Chem. - Eur. J. 2013, 19, 6162−6196. (2) (a) Kovbasyuk, L.; Krämer, R. Chem. Rev. 2004, 104, 3161−3187. (b) Haak, R. M.; Wezenberg, S. J.; Kleij, A. W. Chem. Commun. 2010, 46, 2713−2723. (c) Stoll, R. S.; Hecht, S. Angew. Chem., Int. Ed. 2010, 49, 5054−5075. (d) Kumagai, N.; Shibasaki, M. Catal. Sci. Technol. 13229

DOI: 10.1021/acs.joc.7b02301 J. Org. Chem. 2017, 82, 13220−13230

Article

The Journal of Organic Chemistry (13) Shimoyama, D.; Yamada, H.; Ikeda, T.; Sekiya, R.; Haino, T. Eur. J. Org. Chem. 2016, 2016, 3300−3303. (14) (a) Tunstad, L. M.; Tucker, J. A.; Dalcanale, E.; Weiser, J.; Bryant, J. A.; Sherman, J. C.; Helgeson, R. C.; Knobler, C. B.; Cram, D. J. J. Org. Chem. 1989, 54, 1305−1312. (b) Timmerman, P.; Verboom, W.; Reinhoudt, D. N. Tetrahedron 1996, 52, 2663−2704. (15) (a) Kudo, H.; Hayashi, R.; Mitani, K.; Yokozawa, T.; Kasuga, N. C.; Nishikubo, T. Angew. Chem., Int. Ed. 2006, 45, 7948−7952. (b) Nishikubo, T.; Kudo, H. Japan Patent Kokai, JP2008−280269A, 2008. (16) (a) Salomaa, P.; Kankaanperä, A.; Norin, T. Acta Chem. Scand. 1961, 15, 871−878. (b) Wuts, P. G. M.; Greene, T. W. Greene’s Protective Groups in Organic Synthesis; 4th ed.; Wiley: Hoboken, N.J, 2007. (17) (a) Sheldrick, G. M. Acta Crystallogr., Sect. A: Found. Crystallogr. 2008, 64, 112−122. (b) Spek, A. L. Acta Crystallogr., Sect. D: Biol. Crystallogr. 2009, 65, 148−155. (18) (a) Soncini, P.; Bonsignore, S.; Dalcanale, E.; Ugozzoli, F. J. Org. Chem. 1992, 57, 4608−4612. (b) Mansikkamäki, H.; Nissinen, M.; Rissanen, K. Chem. Commun. 2002, 1902−1903. (c) Aakeröy, C. B.; Chopade, P. D.; Quinn, C. F.; Desper, J. CrystEngComm 2014, 16, 3796−3801. (19) Sutherland, I. O. Annu. Rep. NMR Spectrosc. 1972, 4, 71−235. (20) Claridge, T. D. W. High-Resolution NMR Techniques in Organic Chemistry, Third ed.; Elsevier Science, 2016. (21) (a) Jeener, J.; Meier, B. H.; Bachmann, P.; Ernst, R. R. J. Chem. Phys. 1979, 71, 4546−4553. (b) Perrin, C. L.; Dwyer, T. J. Chem. Rev. 1990, 90, 935−967. (c) Palmer, L. C.; Rebek, J., Jr. Org. Biomol. Chem. 2004, 2, 3051−3059. (d) Pastor, A.; Martínez-Viviente, E. Coord. Chem. Rev. 2008, 252, 2314−2345. (22) Mohamadi, F.; Richards, N. G. J.; Guida, W. C.; Liskamp, R.; Lipton, M.; Caufield, C.; Chang, G.; Hendrickson, T.; Still, W. C. J. Comput. Chem. 1990, 11, 440−467. (23) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; S, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Keith, T.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, Ö .; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09, Revision E.01; Gaussian, Inc.: Wallingford CT, 2016.

13230

DOI: 10.1021/acs.joc.7b02301 J. Org. Chem. 2017, 82, 13220−13230