Volume 50 Number 57 21 July 2014 Pages 7555–7728
ChemComm Chemical Communications www.rsc.org/chemcomm
ISSN 1359-7345
COMMUNICATION Pavel Lhoták et al. Use of residual dipolar couplings in conformational analysis of meta-disubstituted calix[4]arenes
ChemComm View Article Online
Published on 30 April 2014. Downloaded by Temple University on 29/10/2014 13:48:38.
COMMUNICATION
Cite this: Chem. Commun., 2014, 50, 7590 Received 27th March 2014, Accepted 30th April 2014 DOI: 10.1039/c4cc02274b
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Use of residual dipolar couplings in conformational analysis of meta-disubstituted calix[4]arenes† Luka´ˇs Vrzal,a Karolı´na Flı´drova´,b Toma´ˇs Tobrman,b Hana Dvorˇa´kova´a and Pavel Lhota´k*b
www.rsc.org/chemcomm
Dimercuration of tetrapropoxy calix[4]arene followed by a reaction with isoamyl nitrite afforded dinitroso regioisomers with unique substitution patterns. The unusual conformational behaviour of these inherently chiral systems was revealed by the combination of dynamic NMR and residual dipolar coupling (RDC) techniques.
The precisely defined size and/or shape of the cavities together with their well-established chemistry make calixarenes1 very popular building blocks in the design of various receptors.2 Calix[4]arenes, which can be fixed in any of their four basic conformations (cone, partial cone, 1,3-alternate, and 1,2-alternate), represent ideal candidates for the role of molecular scaffolds allowing the introduction of selected functional groups into exactly defined mutual positions. Although the chemistry of calix[4]arenes offers almost countless derivatization possibilities, the general reactivity of the macrocyclic skeleton has notable synthetic restrictions. For example, electrophilic aromatic substitution, the most straightforward strategy for the derivatization of calixarenes, leads exclusively to para substitution of the phenolic subunits.3 Consequently, introduction of substituents into the meta position represents a synthetic challenge, that requires special indirect methods.4,5 During our systematic research on calixarene derivatization we discovered unprecedented access to a meta-substituted organomercurial product by reacting classical calix[4]arene 1 with mercury(II) trifluoroacetate.6 As the meta-substituted calix[4]arenes possess unusual substitution patterns, so far almost inaccessible in calixarene chemistry, the conformational preferences and dynamic behaviour in solution of these isomers are essentially unknown. On the other hand, this knowledge will be very useful in future applications of these systems. In this communication we report
the simple conversion of organomercurial compounds into synthetically useful nitroso intermediates. Moreover, these compounds possess unique conformational behaviour that was discovered by using the residual dipolar coupling (RDC) technique – a method that has been used previously largely only for structure elucidation of biomolecules (proteins and nucleic acids).8 As we recently showed,6b the addition of two equivalents of Hg(TFA)2 to tetrapropoxycalix[4]arene 1 in the cone conformation leads to the formation of the dimercurated product. Fortuitously, this procedure is regioselective as only two out of ten theoretically possible regioisomers are formed (Scheme 1). Both compounds 2 and 3 with distal meta, para and meta, meta arrangement of –HgCl groups represent a unique substitution pattern in calixarene chemistry, which shows potential for construction of novel types of receptors. The direct reaction of chloromercurio compounds with nitrosyl chloride is known but is rarely used.7 However, when nitrosyl chloride was generated in situ from the reaction of isopentyl nitrite and HCl at low temperature (0 1C), the corresponding dinitroso isomers 4 and 5 were obtained in essentially quantitative yields (495%). A model reaction confirmed that no reaction took place under identical conditions with the non-mercurated starting calix[4]arene 1. This new method for the introduction of nitroso groups paves the way for the preparation of inherently chiral amino calixarenes that will be very valuable building blocks in calixarene chemistry.
a
Laboratory of NMR Spectroscopy, Institute of Chemical Technology Prague (ICTP), Technicka´ 5, 166 28, Prague 6, Czech Republic. E-mail: [email protected] b Department of Organic Chemistry, ICTP, Czech Republic. E-mail: [email protected]; Fax: +420-220444288; Tel: +420-220445055 † Electronic supplementary information (ESI) available: Synthetic procedures, NMR spectra, the dynamic NMR study, details of the RDC fitting procedure, and computational data. See DOI: 10.1039/c4cc02274b
7590 | Chem. Commun., 2014, 50, 7590--7592
Scheme 1
Synthesis of dinitroso substituted calix[4]arenes.
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Scheme 2
Pinched cone-pinched cone interconversion of isomer 5.
Calix[4]arenes immobilized in the cone conformation are known to exhibit the so called pinched cone-pinched cone interconversion (Scheme 2).1 The C4v symmetry observed commonly in the NMR spectra of calix[4]arene cone derivatives is, in fact, the time-averaged signal due to the fast chemical exchange between two conformers possessing lower C2v symmetry. As the conformational behaviour of meta-disubstituted calixarenes was unknown, we recorded temperature dependent 1H NMR spectra of 4 and 5 in the range of 298–193 K. A dynamic study of meta, para isomer 4 revealed the behaviour typical for a pinched cone-pinched cone interconversion: time-averaged signals at room temperature, subsequent broadening at lower temperatures, and finally, doubling of some signals under slow exchange conditions at 203 K (Fig. 1). Conversely, the temperature dependent 1H NMR spectra of meta, meta isomer 5 showed dramatically different behaviour, as the almost identical spectra can be seen within the whole temperature range (Fig. 2). This unexpected behaviour indicates that compound 5 probably adopts only one of the two possible pinched cone conformations (Scheme 2). As standard NMR experiments commonly used for
Fig. 1
1
Fig. 2
1
H NMR spectra of 4 (CDCl3, 500 MHz) in the range of 203–298 K.
H NMR spectra of 5 (CDCl3, 500 MHz) in the range of 203–298 K.
This journal is © The Royal Society of Chemistry 2014
ChemComm
conformational studies failed to adequately reveal the structure of 5, we turned our attention to the method of measuring RDCs. The measurement of RDCs has been known for many years and is most commonly used for spatial structure refinement of biomolecules in structural biology.8 Recently the scope of application of RDCs has also been extended to small molecules soluble in organic solvents.9 In the field of calixarenes, only two applications of RDCs have been reported to our knowledge. Klochkov et al. used RDCs for distinguishing between cone and 1,3-alternate isomers of thiacalix[4]arene derivatives10a and our group succeeded in specifying the solution structure of inherently chiral calix[4]arenes.10b The principle of RDCs is an anisotropic through-space dipole– dipole interaction, which is averaged to zero in solution due to fast molecular tumbling. However, if a sample is partially oriented, the anisotropic interactions become observable and contribute to the scalar coupling constants ( J). As these anisotropic interactions depend on the distance of the coupled nuclei and their orientation within the external magnetic field, the value of RDCs contain detailed spatial information. Thus, in contrast to 3J scalar coupling constants and NOEs (ranging up to 5 Å), RDC can provide ‘‘longrange’’ structural information.11 A variety of different anisotropic media have been developed for water soluble biomolecules, including bicelles, micelles, bacteria phages or stretched/compressed polymer gels derived from polyacrylamide. For organic molecules soluble in non-polar solvents, stretched/compressed polymer gels and lyotropic liquid crystalline (LLC) solutions have been designed. LLC media, homopolypeptides poly-g-benzyl-L/D-glutamate (PBLG, PBDG), and poly-g-ethyl-L-glutamate (PELG), as well as the recently introduced polyguanidines, polyisocyanides and polyacetylenes, induce the appropriate degree of alignment, and thus enable the precise extraction of coupling constants.12 To obtain the RDC data we prepared samples of compound 5 in three different liquid crystalline phases (Fig. 3): (A) phenylalaninederived polyacetylene,13 (B) poly-g-benzyl-D-glutamate (high molecular weight PBDG),14 and (C) commercial poly-g-benzyl15 L-glutamate (PBLG). RDCs were extracted from 13C coupled or CLIP-HSQC spectra. RDCs were calculated using the following equation: 1TC–H = 21DC–H + 1 JC–H, where 1TC–H is the one-bond heteronuclear coupling constant (total splitting) elucidated from coupled 13C NMR or CLIP-HSQC spectra of an anisotropic solution, 1DC–H is the one-bond heteronuclear residual dipolar coupling constant, and 1JC–H represents the one-bond heteronuclear scalar coupling constant elucidated from coupled 13C NMR or CLIP-HSQC spectra of an isotropic solution. First, we examined an oriented sample of meta, meta isomer 5 in the recently reported phenylalanine-derived polyacetylene13
Fig. 3
Selected alignment media structures.
Chem. Commun., 2014, 50, 7590--7592 | 7591
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are excellent alignment media for measuring of the RDCs of calixarenes in CDCl3. The obtained RDCs allow us to unambiguously conclude, that calix[4]arene 5 adopts a specific pinched cone conformation in solution, with both nitroso groups on the flattened aromatic rings. This conformational preference represents unique behaviour in calixarene chemistry indicating the unusual properties of calix[4]arenes with the unprecedented meta, meta substitution pattern. This research was supported by the Czech Science Foundation (P207/12/2027).
Notes and references
Fig. 4 DFT optimized structures, 5(I) and 5(II), and correlations between calculated and experimental RDCs in polyacetylene alignment medium A.
(A), an LLC medium inducing a lower degree of alignment, in comparison to PBLG (B).16 To generate our initial input structure 5(I) for ab initio calculations (B3LYP/6-31G* level in Gaussian03†), X-ray diffraction data17 of an intermediate chloromercurio derivative 3 were utilized. Subsequently, the optimized structure of 5 (Fig. 4) together with the experimental one-bond RDCs (1DC–H) were used for the fitting procedure in the program PALES.18 Surprisingly, the comparison of the observed and the back calculated RDCs resulted in a very bad linear correlation (Fig. 4). As the experimental data were very precisely extracted, the only explanation for this unsatisfactory correlation is the wrong input structure. Therefore, we modified the input structure to 5(II) by moving of the nitroso groups from the vertical rings to the flattened ones. In this case the fitting of the ab initio-optimized structure in PALES provided an excellent correlation between experimental and back calculated RDCs (Fig. 4). The B3LYP/6-31G* calculation also confirmed that the pinched cone 5(II) is favoured over 5(I) by 18.13 kJ mol 1. The same fitting procedure was performed with the other samples of alignment media B and C. Surprisingly, both the high molecular weight PBDG (B) and PBLG with a lower molecular weight (C) afforded almost identical results to medium A. Thus, regardless of the degree of alignment, the accuracy of extracting the coupling constants, and also the fitting results were similar. Moreover, analysis of the alignment tensors indicated a similar orientation of calix[4]arene 5 within the magnetic field in all studied media.† In summary, we have shown that the RDC techniques can be successfully applied to accurately describe the dynamic behaviour of relatively small molecules. The phenylalaninederived polyacetylene (A) and poly-g-benzyl-glutamates (B, C)
7592 | Chem. Commun., 2014, 50, 7590--7592
1 C. D. Gutsche, Calixarenes an Introduction, The Royal Society of Chemistry, Thomas Graham House, Cambridge, 2nd edn, 2008. 2 (a) Calixarenes in the Nanoworld, ed. J. Vicens, J. Harrowfield and L. Backlouti, Springer, Dordrecht, 2007; (b) L. Mandolini and R. Ungaro, Calixarenes in Action, Imperial College Press, London, 2000. ¨hmer, Angew. Chem., Int. Ed. Engl., 1995, 34, 713. 3 V. Bo 4 One can use the presence of ortho-directing functional group in the para position of a calixarene skeleton: (a) S. A. Herbert and G. E. Arnott, Org. Lett., 2010, 12, 4600; (b) S. A. Herbert and G. E. Arnott, Org. Lett., 2009, 11, 4986; (c) Z. X. Xu, G. K. Li, C. F. Chen and Z. T. Huang, Tetrahedron, 2008, 64, 8668; (d) Z. X. Xu, C. Zhang, C. F. Chen and Z. T. Huang, Org. Lett., 2007, 9, 4447; (e) R. Miao, Q. Y. Zheng and C. F. Chen, J. Org. Chem., 2005, 70, 7662; ( f ) M. Mascal, R. Warmuth, R. T. Naven, R. A. Edwards, M. B. Hursthouse and D. E. Hibbs, J. Chem. Soc., Perkin Trans. 1, 1999, 3435. 5 Several meta-substituted calix[4]arenes were prepared recently by the silver-mediated rearrangement of so-called p-bromodienone derivatives. The synthetic applicability of this procedure is limited by low yields and the fact, that the method is based on the unsubstituted lower rim (free phenol): (a) C. Gatea, F. Troisi, C. Talotta, T. Pierro and P. Neri, J. Org. Chem., 2012, 77, 3634; (b) F. Troisi, T. Pierro, C. Gaeta and P. Neri, Tetrahedron Lett., 2009, 50, 4416. ´, S. Bo ¨hm ˇ, K. Flı´drova ´, J. Sy´kora, I. Cı´sarˇova 6 (a) P. Slavı´k, M. Dudic ´k, Org. Lett., 2012, 14, 3628; (b) K. Flı´drova ´, S. Bo ¨hm, and P. Lhota ´, V. Eigner and P. Lhota ´k, Org. Lett., 2014, 16, 138. H. Dvorˇ´ akova 7 L. I. Smith and F. L. Taylor, J. Am. Chem. Soc., 1935, 57, 2460. 8 J. R. Tolman, J. M. Flanagan, M. A. Kennedy and J. H. Prestegard, Proc. Natl. Acad. Sci. U. S. A., 1995, 92, 9279. ¨we and B. Luy, Annu. Rep. NMR Spectrosc., 2009, 9 G. Kummerlo 68, 193. 10 (a) V. V. Klochkov, B. I. Khairutdinov, A. V. Klochkov, M. S. Tagirov, C. M. Thiele, S. Berger, I. S. Vershinina, I. I. Stoikov, I. S. Antipin and A. I. Konovalov, Russ. Chem. Bull., 2004, 53, 1466; (b) J. Holub, ´ and P. Lhota ´k, Chem. Commun., V. Eigner, L. Vrzal, H. Dvorˇ´ akova 2013, 49, 2798. 11 C. M. Thiele, J. Org. Chem., 2008, 5673. ¨we and B. Luy, TrAC, Trends Anal. Chem., 2009, 28, 483. 12 G. Kummerlo 13 A. Krupp and M. Reggelin, Magn. Reson. Chem., 2012, 50, S45. 14 A. Marx, V. Schmidts and C. M. Thiele, Magn. Reson. Chem., 2009, 47, 734. 15 A. Marx and C. M. Thiele, Chem. – Eur. J., 2009, 15, 254. 16 M. Dama and S. Berger, Tetrahedron Lett., 2012, 53, 6439. 17 Compound 3 adopts the pinched cone conformation in the solid state with HgCl groups on vertical aromatic rings. This arrangement is stabilized via strong intramolecular Hg p interactions with two neighbour aromatic carbon atoms (Z2 bonding) – see ref. 6b. 18 M. Zweckstetter, Nat. Protocols, 2008, 3, 679.
This journal is © The Royal Society of Chemistry 2014
ChemComm Chemical Communications www.rsc.org/chemcomm
ISSN 1359-7345
COMMUNICATION Pavel Lhoták et al. Use of residual dipolar couplings in conformational analysis of meta-disubstituted calix[4]arenes
ChemComm View Article Online
Published on 30 April 2014. Downloaded by Temple University on 29/10/2014 13:48:38.
COMMUNICATION
Cite this: Chem. Commun., 2014, 50, 7590 Received 27th March 2014, Accepted 30th April 2014 DOI: 10.1039/c4cc02274b
View Journal | View Issue
Use of residual dipolar couplings in conformational analysis of meta-disubstituted calix[4]arenes† Luka´ˇs Vrzal,a Karolı´na Flı´drova´,b Toma´ˇs Tobrman,b Hana Dvorˇa´kova´a and Pavel Lhota´k*b
www.rsc.org/chemcomm
Dimercuration of tetrapropoxy calix[4]arene followed by a reaction with isoamyl nitrite afforded dinitroso regioisomers with unique substitution patterns. The unusual conformational behaviour of these inherently chiral systems was revealed by the combination of dynamic NMR and residual dipolar coupling (RDC) techniques.
The precisely defined size and/or shape of the cavities together with their well-established chemistry make calixarenes1 very popular building blocks in the design of various receptors.2 Calix[4]arenes, which can be fixed in any of their four basic conformations (cone, partial cone, 1,3-alternate, and 1,2-alternate), represent ideal candidates for the role of molecular scaffolds allowing the introduction of selected functional groups into exactly defined mutual positions. Although the chemistry of calix[4]arenes offers almost countless derivatization possibilities, the general reactivity of the macrocyclic skeleton has notable synthetic restrictions. For example, electrophilic aromatic substitution, the most straightforward strategy for the derivatization of calixarenes, leads exclusively to para substitution of the phenolic subunits.3 Consequently, introduction of substituents into the meta position represents a synthetic challenge, that requires special indirect methods.4,5 During our systematic research on calixarene derivatization we discovered unprecedented access to a meta-substituted organomercurial product by reacting classical calix[4]arene 1 with mercury(II) trifluoroacetate.6 As the meta-substituted calix[4]arenes possess unusual substitution patterns, so far almost inaccessible in calixarene chemistry, the conformational preferences and dynamic behaviour in solution of these isomers are essentially unknown. On the other hand, this knowledge will be very useful in future applications of these systems. In this communication we report
the simple conversion of organomercurial compounds into synthetically useful nitroso intermediates. Moreover, these compounds possess unique conformational behaviour that was discovered by using the residual dipolar coupling (RDC) technique – a method that has been used previously largely only for structure elucidation of biomolecules (proteins and nucleic acids).8 As we recently showed,6b the addition of two equivalents of Hg(TFA)2 to tetrapropoxycalix[4]arene 1 in the cone conformation leads to the formation of the dimercurated product. Fortuitously, this procedure is regioselective as only two out of ten theoretically possible regioisomers are formed (Scheme 1). Both compounds 2 and 3 with distal meta, para and meta, meta arrangement of –HgCl groups represent a unique substitution pattern in calixarene chemistry, which shows potential for construction of novel types of receptors. The direct reaction of chloromercurio compounds with nitrosyl chloride is known but is rarely used.7 However, when nitrosyl chloride was generated in situ from the reaction of isopentyl nitrite and HCl at low temperature (0 1C), the corresponding dinitroso isomers 4 and 5 were obtained in essentially quantitative yields (495%). A model reaction confirmed that no reaction took place under identical conditions with the non-mercurated starting calix[4]arene 1. This new method for the introduction of nitroso groups paves the way for the preparation of inherently chiral amino calixarenes that will be very valuable building blocks in calixarene chemistry.
a
Laboratory of NMR Spectroscopy, Institute of Chemical Technology Prague (ICTP), Technicka´ 5, 166 28, Prague 6, Czech Republic. E-mail: [email protected] b Department of Organic Chemistry, ICTP, Czech Republic. E-mail: [email protected]; Fax: +420-220444288; Tel: +420-220445055 † Electronic supplementary information (ESI) available: Synthetic procedures, NMR spectra, the dynamic NMR study, details of the RDC fitting procedure, and computational data. See DOI: 10.1039/c4cc02274b
7590 | Chem. Commun., 2014, 50, 7590--7592
Scheme 1
Synthesis of dinitroso substituted calix[4]arenes.
This journal is © The Royal Society of Chemistry 2014
View Article Online
Communication
Published on 30 April 2014. Downloaded by Temple University on 29/10/2014 13:48:38.
Scheme 2
Pinched cone-pinched cone interconversion of isomer 5.
Calix[4]arenes immobilized in the cone conformation are known to exhibit the so called pinched cone-pinched cone interconversion (Scheme 2).1 The C4v symmetry observed commonly in the NMR spectra of calix[4]arene cone derivatives is, in fact, the time-averaged signal due to the fast chemical exchange between two conformers possessing lower C2v symmetry. As the conformational behaviour of meta-disubstituted calixarenes was unknown, we recorded temperature dependent 1H NMR spectra of 4 and 5 in the range of 298–193 K. A dynamic study of meta, para isomer 4 revealed the behaviour typical for a pinched cone-pinched cone interconversion: time-averaged signals at room temperature, subsequent broadening at lower temperatures, and finally, doubling of some signals under slow exchange conditions at 203 K (Fig. 1). Conversely, the temperature dependent 1H NMR spectra of meta, meta isomer 5 showed dramatically different behaviour, as the almost identical spectra can be seen within the whole temperature range (Fig. 2). This unexpected behaviour indicates that compound 5 probably adopts only one of the two possible pinched cone conformations (Scheme 2). As standard NMR experiments commonly used for
Fig. 1
1
Fig. 2
1
H NMR spectra of 4 (CDCl3, 500 MHz) in the range of 203–298 K.
H NMR spectra of 5 (CDCl3, 500 MHz) in the range of 203–298 K.
This journal is © The Royal Society of Chemistry 2014
ChemComm
conformational studies failed to adequately reveal the structure of 5, we turned our attention to the method of measuring RDCs. The measurement of RDCs has been known for many years and is most commonly used for spatial structure refinement of biomolecules in structural biology.8 Recently the scope of application of RDCs has also been extended to small molecules soluble in organic solvents.9 In the field of calixarenes, only two applications of RDCs have been reported to our knowledge. Klochkov et al. used RDCs for distinguishing between cone and 1,3-alternate isomers of thiacalix[4]arene derivatives10a and our group succeeded in specifying the solution structure of inherently chiral calix[4]arenes.10b The principle of RDCs is an anisotropic through-space dipole– dipole interaction, which is averaged to zero in solution due to fast molecular tumbling. However, if a sample is partially oriented, the anisotropic interactions become observable and contribute to the scalar coupling constants ( J). As these anisotropic interactions depend on the distance of the coupled nuclei and their orientation within the external magnetic field, the value of RDCs contain detailed spatial information. Thus, in contrast to 3J scalar coupling constants and NOEs (ranging up to 5 Å), RDC can provide ‘‘longrange’’ structural information.11 A variety of different anisotropic media have been developed for water soluble biomolecules, including bicelles, micelles, bacteria phages or stretched/compressed polymer gels derived from polyacrylamide. For organic molecules soluble in non-polar solvents, stretched/compressed polymer gels and lyotropic liquid crystalline (LLC) solutions have been designed. LLC media, homopolypeptides poly-g-benzyl-L/D-glutamate (PBLG, PBDG), and poly-g-ethyl-L-glutamate (PELG), as well as the recently introduced polyguanidines, polyisocyanides and polyacetylenes, induce the appropriate degree of alignment, and thus enable the precise extraction of coupling constants.12 To obtain the RDC data we prepared samples of compound 5 in three different liquid crystalline phases (Fig. 3): (A) phenylalaninederived polyacetylene,13 (B) poly-g-benzyl-D-glutamate (high molecular weight PBDG),14 and (C) commercial poly-g-benzyl15 L-glutamate (PBLG). RDCs were extracted from 13C coupled or CLIP-HSQC spectra. RDCs were calculated using the following equation: 1TC–H = 21DC–H + 1 JC–H, where 1TC–H is the one-bond heteronuclear coupling constant (total splitting) elucidated from coupled 13C NMR or CLIP-HSQC spectra of an anisotropic solution, 1DC–H is the one-bond heteronuclear residual dipolar coupling constant, and 1JC–H represents the one-bond heteronuclear scalar coupling constant elucidated from coupled 13C NMR or CLIP-HSQC spectra of an isotropic solution. First, we examined an oriented sample of meta, meta isomer 5 in the recently reported phenylalanine-derived polyacetylene13
Fig. 3
Selected alignment media structures.
Chem. Commun., 2014, 50, 7590--7592 | 7591
View Article Online
ChemComm
Communication
Published on 30 April 2014. Downloaded by Temple University on 29/10/2014 13:48:38.
are excellent alignment media for measuring of the RDCs of calixarenes in CDCl3. The obtained RDCs allow us to unambiguously conclude, that calix[4]arene 5 adopts a specific pinched cone conformation in solution, with both nitroso groups on the flattened aromatic rings. This conformational preference represents unique behaviour in calixarene chemistry indicating the unusual properties of calix[4]arenes with the unprecedented meta, meta substitution pattern. This research was supported by the Czech Science Foundation (P207/12/2027).
Notes and references
Fig. 4 DFT optimized structures, 5(I) and 5(II), and correlations between calculated and experimental RDCs in polyacetylene alignment medium A.
(A), an LLC medium inducing a lower degree of alignment, in comparison to PBLG (B).16 To generate our initial input structure 5(I) for ab initio calculations (B3LYP/6-31G* level in Gaussian03†), X-ray diffraction data17 of an intermediate chloromercurio derivative 3 were utilized. Subsequently, the optimized structure of 5 (Fig. 4) together with the experimental one-bond RDCs (1DC–H) were used for the fitting procedure in the program PALES.18 Surprisingly, the comparison of the observed and the back calculated RDCs resulted in a very bad linear correlation (Fig. 4). As the experimental data were very precisely extracted, the only explanation for this unsatisfactory correlation is the wrong input structure. Therefore, we modified the input structure to 5(II) by moving of the nitroso groups from the vertical rings to the flattened ones. In this case the fitting of the ab initio-optimized structure in PALES provided an excellent correlation between experimental and back calculated RDCs (Fig. 4). The B3LYP/6-31G* calculation also confirmed that the pinched cone 5(II) is favoured over 5(I) by 18.13 kJ mol 1. The same fitting procedure was performed with the other samples of alignment media B and C. Surprisingly, both the high molecular weight PBDG (B) and PBLG with a lower molecular weight (C) afforded almost identical results to medium A. Thus, regardless of the degree of alignment, the accuracy of extracting the coupling constants, and also the fitting results were similar. Moreover, analysis of the alignment tensors indicated a similar orientation of calix[4]arene 5 within the magnetic field in all studied media.† In summary, we have shown that the RDC techniques can be successfully applied to accurately describe the dynamic behaviour of relatively small molecules. The phenylalaninederived polyacetylene (A) and poly-g-benzyl-glutamates (B, C)
7592 | Chem. Commun., 2014, 50, 7590--7592
1 C. D. Gutsche, Calixarenes an Introduction, The Royal Society of Chemistry, Thomas Graham House, Cambridge, 2nd edn, 2008. 2 (a) Calixarenes in the Nanoworld, ed. J. Vicens, J. Harrowfield and L. Backlouti, Springer, Dordrecht, 2007; (b) L. Mandolini and R. Ungaro, Calixarenes in Action, Imperial College Press, London, 2000. ¨hmer, Angew. Chem., Int. Ed. Engl., 1995, 34, 713. 3 V. Bo 4 One can use the presence of ortho-directing functional group in the para position of a calixarene skeleton: (a) S. A. Herbert and G. E. Arnott, Org. Lett., 2010, 12, 4600; (b) S. A. Herbert and G. E. Arnott, Org. Lett., 2009, 11, 4986; (c) Z. X. Xu, G. K. Li, C. F. Chen and Z. T. Huang, Tetrahedron, 2008, 64, 8668; (d) Z. X. Xu, C. Zhang, C. F. Chen and Z. T. Huang, Org. Lett., 2007, 9, 4447; (e) R. Miao, Q. Y. Zheng and C. F. Chen, J. Org. Chem., 2005, 70, 7662; ( f ) M. Mascal, R. Warmuth, R. T. Naven, R. A. Edwards, M. B. Hursthouse and D. E. Hibbs, J. Chem. Soc., Perkin Trans. 1, 1999, 3435. 5 Several meta-substituted calix[4]arenes were prepared recently by the silver-mediated rearrangement of so-called p-bromodienone derivatives. The synthetic applicability of this procedure is limited by low yields and the fact, that the method is based on the unsubstituted lower rim (free phenol): (a) C. Gatea, F. Troisi, C. Talotta, T. Pierro and P. Neri, J. Org. Chem., 2012, 77, 3634; (b) F. Troisi, T. Pierro, C. Gaeta and P. Neri, Tetrahedron Lett., 2009, 50, 4416. ´, S. Bo ¨hm ˇ, K. Flı´drova ´, J. Sy´kora, I. Cı´sarˇova 6 (a) P. Slavı´k, M. Dudic ´k, Org. Lett., 2012, 14, 3628; (b) K. Flı´drova ´, S. Bo ¨hm, and P. Lhota ´, V. Eigner and P. Lhota ´k, Org. Lett., 2014, 16, 138. H. Dvorˇ´ akova 7 L. I. Smith and F. L. Taylor, J. Am. Chem. Soc., 1935, 57, 2460. 8 J. R. Tolman, J. M. Flanagan, M. A. Kennedy and J. H. Prestegard, Proc. Natl. Acad. Sci. U. S. A., 1995, 92, 9279. ¨we and B. Luy, Annu. Rep. NMR Spectrosc., 2009, 9 G. Kummerlo 68, 193. 10 (a) V. V. Klochkov, B. I. Khairutdinov, A. V. Klochkov, M. S. Tagirov, C. M. Thiele, S. Berger, I. S. Vershinina, I. I. Stoikov, I. S. Antipin and A. I. Konovalov, Russ. Chem. Bull., 2004, 53, 1466; (b) J. Holub, ´ and P. Lhota ´k, Chem. Commun., V. Eigner, L. Vrzal, H. Dvorˇ´ akova 2013, 49, 2798. 11 C. M. Thiele, J. Org. Chem., 2008, 5673. ¨we and B. Luy, TrAC, Trends Anal. Chem., 2009, 28, 483. 12 G. Kummerlo 13 A. Krupp and M. Reggelin, Magn. Reson. Chem., 2012, 50, S45. 14 A. Marx, V. Schmidts and C. M. Thiele, Magn. Reson. Chem., 2009, 47, 734. 15 A. Marx and C. M. Thiele, Chem. – Eur. J., 2009, 15, 254. 16 M. Dama and S. Berger, Tetrahedron Lett., 2012, 53, 6439. 17 Compound 3 adopts the pinched cone conformation in the solid state with HgCl groups on vertical aromatic rings. This arrangement is stabilized via strong intramolecular Hg p interactions with two neighbour aromatic carbon atoms (Z2 bonding) – see ref. 6b. 18 M. Zweckstetter, Nat. Protocols, 2008, 3, 679.
This journal is © The Royal Society of Chemistry 2014
