Synthesis of Mechanically Planar Chiral rac-[2]Rotaxanes by

Letter pubs.acs.org/OrgLett

Synthesis of Mechanically Planar Chiral rac-[2]Rotaxanes by Partitioning of an Achiral [2]Rotaxane: Stereoinversion Induced by Shuttling Yuta Mochizuki,† Katsuhiko Ikeyatsu,† Yuichiro Mutoh,† Shoichi Hosoya,‡ and Shinichi Saito*,† †

Department of Chemistry, Faculty of Science, Tokyo University of Science, Kagurazaka, Shinjuku, Tokyo 162-8601, Japan Research Center for Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan

‡

S Supporting Information *

ABSTRACT: Mechanically planar chiral [2]rotaxanes were synthesized by the introduction of bulky pyrrole moieties into the axle component of an achiral [2]rotaxane. The enantiomers were separated by chiral HPLC. The shuttling of the ring component between the two compartments at high temperature induced the stereoinversion of the mechanically planar chiral [2]rotaxane. The rate of the stereoinversion was studied quantitatively, and the kinetic parameters were determined.

[2]Rotaxane is an interlocked compound which consists of a ring and an axle component. The bulky blocking groups at both ends of the axle component prevent the dissociation of the two components.1 The introduction of chirality to the rotaxane is expected to expand the application of rotaxanes, such as catalysts, materials, and molecular machines. A simple method for the introduction of chirality to [2]rotaxanes is to install a chiral functional group to the ring or axle component.2 Alternatively, a mechanically planar chiral [2]rotaxane could be synthesized when an axle with low symmetry (C∞v or Cs symmetry) was threaded through a Cs -symmetric ring component (Figure 1a).3 The presence of this type of stereoisomers has been discussed by Schill.3a The first isolation of the enantiomers of a mechanically planar chiral [2]rotaxane was realized by Vögtle and Okamoto et al. They applied the template-capping strategy for the synthesis of a mechanically planar chiral [2]rotaxane, and the enantiomers were separated by chiral HPLC.3c Leigh et al. reported the stereoselective synthesis and catalytic activity of mechanically point-chiral [2]rotaxanes with Cs-symmetric axle component.3n,t Chirality was introduced to the [2]rotaxane by preventing the shuttling of the ring component. The stereoselective synthesis of chiral [2]rotaxanes was reported by Takata et al.3k and Goldup et al.3s The restricted conformational change in the ring component resulted in the formation of chiral [2]rotaxanes.4 The stereoisomers observed in some [2]rotaxanes could be considered as conformational isomers.5 To the best of our knowledge, the low symmetry (C∞v or Cs symmetry) of the axle component has been a requirement for the synthesis of a mechanically planar chiral [2]rotaxane, and a mechanically planar chiral [2]rotaxane with a C2v-symmetric axle component has not been reported to date.6 Recently, we reported the synthesis of partitioned [2]rotaxanes with an N-substituted pyrrole moiety.7 The move© XXXX American Chemical Society

Figure 1. (a) Mechanically planar chiral [2]rotaxane composed of a C∞v-symmetric axle component and a Cs-symmetric ring component. (b) Mechanically planar chiral [2]rotaxane composed of a C2vsynmetric axle component and a Cs-symmetric ring component. Direct stereoinversion would proceed by the shuttling of the ring component.

ment of the ring component across the pyrrole moiety (shuttling) was inhibited when a bulky substituent was introduced to the pyrrole moiety of the [2]rotaxane. The successful synthesis of partitioned [2]rotaxanes prompted us to synthesize a mechanically planar chiral [2]rotaxane with a C2vsymmetric axle component and a Cs-symmetric ring component (Figure 1b). In this paper, we report the synthesis of mechanically planar chiral [2]rotaxanes with new symmetry. We determined the kinetic parameters for the racemization of Received: July 5, 2017

A

DOI: 10.1021/acs.orglett.7b02043 Org. Lett. XXXX, XXX, XXX−XXX

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Organic Letters Scheme 1. Synthesis of Mechanically Planar Chiral [2]Rotaxanes 5a,b

the mechanically planar chiral [2]rotaxanes, which was induced by the shuttling of the ring component. The synthesis of mechanically planar chiral [2]rotaxanes 5a,b is described in Scheme 1. The reaction of 18 with CuI gave a Cssymmetric phenanthroline complex 1-CuI in 92% yield.9 The threading reaction of 1-CuI and 210 proceeded in the presence of K2CO3 and I2 in xylene at 130 °C. The crude mixture was treated with ammonia11,12 to remove the Cu ion, and [2]rotaxane 3 was isolated in 75% yield. The 1H NMR spectra of 3 and related compounds are shown in Figure 2. Many signals shifted upfield when the ring component 1 (or 613) was converted to [2]rotaxane 3 (e.g., Ha-Hd, Ha′-Hd′, HB). Interestingly, the difference of the chemical shifts of magnetically nonequivalent protons was larger when 1 was converted to 3. For example, the doublet, which was observed at 7.09 ppm, was assigned as the signals of He and He′ in the NMR spectrum of 1. On the other hand, two doublets, which correspond to the signals of He and He′, were observed at 7.00 and 6.94 ppm in the NMR spectrum of 3. Next, [2]rotaxane 5a was synthesized in 76% yield by treating 3 with 20 equiv of p-(4cyclohexylphenyl)aniline (4a) in the presence of CuCl at 120 °C and removing the Cu ion.7 The reaction of 3 with 4cyclohexylaniline (4b) gave 5b in 84% yield. The 1H NMR spectra of 3 and 5a are shown in Figure 3. The two blocking groups (tris(4-cyclohexylbiphenyl)methyl groups) of 5a are magnetically nonequivalent. While four doublets (HC−HF) were observed in the spectrum of 3, eight doublets (HC1−HF1 and HC2−HF2) were observed at 7.5−7.2 ppm in the 1H NMR spectrum of 5a. The observed result could be explained in terms of the inhibited movement of the ring component across the pyrrole moiety.7 Another important property introduced to 5a is chirality. While [2]rotaxane 3 is achiral, the partitioned [2]rotaxanes 5a,b are chiral. As a result, the methyl groups bound to the silicon atom of 5a (Si−Me1 and Si−Me2) are magnetically nonequivalent, and they were observed as two singlets at 0.142 and 0.136 ppm (Scheme 1). The enantiomers of 5a were separated by chiral HPLC (conditions: CHIRALPAK ID (0.46 cm i.d. × 25 cm L); eluent

Figure 2. 1H NMR spectra of ring component 1, [2]rotaxane 3, and axle component 6 (500 MHz, CDCl3, 298 K).

hexane/CH2Cl2/MeOH/HNEt2 = 78:22:1:0.1, flow rate; 0.4 mL min−1). The CD spectrum of the enantiomers display opposite Cotton effects (Figure 4). The fast eluting enantiomer B

DOI: 10.1021/acs.orglett.7b02043 Org. Lett. XXXX, XXX, XXX−XXX

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Organic Letters

Figure 5. Chiral HPLC analysis of the racemization of [CD(+)-360]5a in (CHCl2)2 at 413 K (detection, 270 nm).

Table 1. Kinetic Parameters for the Stereoinversion of [2]Rotaxane [CD(+)-360]-5a in (CHCl2)2

Figure 3. 1H NMR spectra of the [2]rotaxane 3 and [2]rotaxane 5a (500 MHz, CDCl3, 298 K).

T (K)

was defined as [CD(+)-360]-5a, and the slow-eluting enantiomer was defined as [CD(−)-360]-5a.14

398 403 408 413 a

kraca (s−1) 4.60 6.30 7.51 1.01

× × × ×

t1/2racb (h)

ΔG‡ (kJ mol−1)

4.19 3.06 2.56 1.91

134 134 136 136

−5

10 10−5 10−5 10−4

The rate constant of racemization. bThe half-life of racemization.

the racemization of 5b. It is noteworthy that these parameters could be determined by using mechanically planar chiral [2]rotaxanes: previous attempts to determine these parameters by VT-NMR of achiral [2]rotaxanes were unsuccessful due to the low rate of the shuttling in the NMR time scale.7 In summary, we synthesized mechanically planar chiral [2]rotaxanes with unprecedented structures by partitioning strategy. The stereoinversion of the mechanically planar chiral [2]rotaxanes, which was induced by the shuttling of the ring component, was observed for the first time, and the reaction was studied quantitatively. The study would contribute to the understanding of the chemistry of mechanically planar chiral [2]rotaxanes.

Figure 4. CD spectra of [2]rotaxane [CD(+)-360]-5a (96% ee) and [CD(−)-360]-5a (95% ee) in CHCl3.

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Due to the presence of a bulky substituent bound to the pyrrole moiety, the racemization of [CD(+)-360]-5a, i.e., the shuttling of the ring component across the pyrrole moiety, did not proceed at rt in CHCl3 or (CHCl2)2. The result is in accordance with our previous results.7 When a solution of [CD(+)-360]-5a was heated in (CHCl2)2 at 413 K (140 °C), however, the progress of the racemization was observed (Figure 5). We determined the kinetic parameters of the shuttling process by observing the rate constant of the racemization reaction at different temperatures (Table 1). An Eyring plot of the rate constants krac provided the following activation parameters: ΔH⧧(5a) = 65.9 kJ mol−1 and ΔS⧧(5a) = −170 J K−1 mol−1.15 As expected, the rate of the racemization of 5b was faster compared to that of 5a, and the activation parameters were determined as follows: ΔH⧧(5b) = 70.4 kJ mol−1 and ΔS⧧(5b) = −120 J K−1 mol−1.8 The larger value of ΔS⧧ in the racemization of 5b could be explained in terms of the presence of a smaller partition (4-cyclohexylphenyl group) in 5b: the transition state of the shuttling process would be less ordered in

ASSOCIATED CONTENT

* Supporting Information S

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.7b02043. Experimental procedures and NMR spectra (1H, 13C) for new compounds (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

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

The authors declare no competing financial interest. C

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ACKNOWLEDGMENTS This work was supported in part by JSPS KAKENHI Grant No. JP26410125.

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