ChemComm View Article Online
Published on 29 October 2013. Downloaded by University of Pittsburgh on 29/10/2014 12:13:24.
COMMUNICATION
Cite this: Chem. Commun., 2013, 49, 11412 Received 4th September 2013, Accepted 15th October 2013 DOI: 10.1039/c3cc46754f
View Journal | View Issue
A helically twisted imine macrocycle that allows for determining the absolute configuration of a-amino carboxylates† Min Jun Kim, Ye Rin Choi, Hae-Geun Jeon, Philjae Kang, Moon-Gun Choi and Kyu-Sung Jeong*
www.rsc.org/chemcomm
Binding of a-amino carboxylates to a helically twisted imine macrocycle based on the indolocarbazole scaffold gives rise to characteristic circular dichroism spectra, and the patterns of the Cotton effects are consistent with the absolute configuration of a-amino carboxylates.
Circular dichroism (CD) spectroscopy is a convenient and powerful technique to investigate the chirality of chemical species, including the absolute configuration of stereocenters, the screw sense of helically twisted species, enantiomeric excesses (ee’s), and stereodynamic conformational changes. For this purpose, exciton coupled circular dichroism (ECCD) has been widely implemented for synthetic molecules that possess two or more interacting chromophores oriented in a twisted array.1 Several molecular probes for chirality sensing have been described such as bisporphyrins,2 triaryl propellers,3 arylethynyl foldamers,4 etc.5 Indolocarbazoles are a class of fully conjugated aromatic heterocycles that show strong absorption in the UV-visible region. They have two indole-type NH protons which are able to form strong hydrogen bonds and have been utilized as useful building blocks for synthetic anion receptors.6 Previously, we demonstrated that indolocarbazole foldamers could bind anions with high affinity and selectivity and fold to form helical conformations in solution and in the solid state.7 It was also shown that the helical orientation of an indolocarbazole dimer with chiral residues could be reversibly and completely inverted by anion stimulation, thus functioning as a chiroptical molecular switch.8 Herein, we extend our work to develop a stereodynamic probe that allows for determining the absolute stereochemistries and ee’s of a-aminocarboxylates based on the CD signals. The chirality sensing is ascribed to the helically twisted nature of imine macrocycles 3, and the helical bias is induced by hydrogen bonding of chiral carboxylates to the internal cavity of 3b. Department of Chemistry, Yonsei University, Seoul 120-749, Korea. E-mail: [email protected]; Fax: +82-2-364-7050; Tel: +82-2-2123-2643 † Electronic supplementary information (ESI) available: Characterization data of the new compound, NMR studies, circular dichroism studies, computer modeling, and X-ray crystallographic data. CCDC 951760. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c3cc46754f
11412
Chem. Commun., 2013, 49, 11412--11414
Compound 1 consists of two indolocarbazole chromophores connected through a butadiynyl spacer and two benzaldehyde units at the ends (Scheme 1). In particular, ortho-ethynylbenzaldehyde was chosen to form imine macrocycles with 1,2-diamines.9 The methoxy substituents help increase the solubility in organic solvents. Synthesis of 1 is straightforward and details are summarized in the ESI.† The formation of imine macrocycle 3a between 1 (1 mM) and cyclohexane-(1S,2S)-diamines(2a) (B2 equiv.) was first examined in CD2Cl2 at room temperature by 1H NMR spectroscopy (Fig. 1a). As a template, acetate was used because the hydrogen bonding between 1 and the acetate ion leads to the helical folding of 1. Consequently, the two aldehyde groups are brought in close proximity facilitating formation of imine macrocycle 3a.
Scheme 1 Molecular structures of compound 1, 1,2-diamines 2a and 2b, and imine macrocycles 3a and 3b.
This journal is
c
The Royal Society of Chemistry 2013
View Article Online
Published on 29 October 2013. Downloaded by University of Pittsburgh on 29/10/2014 12:13:24.
Communication
ChemComm
Fig. 2 Two views of the crystal structure of (R,R)-3a complexed with tetrabutylammonium acetate. In the crystal, 3a has P-helix, and the hydrogen bond distances of N3 O97, N23 O98, N6 O97 and N26 O98 are 3.19, 3.03, 2.85 and 2.85 Å, respectively. Countercations and hydrogen atoms except NH protons have been omitted for clarity.
Fig. 1 (a) Partial 1H NMR spectra (400 MHz, CD2Cl2, 25 1C) for the formation of 3a between 1 and (1S,2S)-2a in the presence of tetrabutylammonium acetate. (b) CD spectra (5.0 10 5 M in CH2Cl2, 25 1C) of 3a derived from cyclohexane(1R,2R)-diamine (blue) and its enantiomer (red).
The reaction was completed within 30 min in the presence of tetrabutylammonium acetate (2 equiv.), affording only one set of 1H NMR signals corresponding to the molecular structure of 3a. However, the reaction was complicated in the absence of the acetate ion possibly due to the formation of the 1 : 2 (1/diamine) condensation product and higher oligomers (Fig. S1, ESI†). Moreover, the reaction was significantly slower, having not completed after several hours, which implies that the acetate ion acts as a template as well as facilitates the formation of imine macrocycle 3a. The formation of 3a was also investigated by CD spectroscopy (Fig. 1b). When diamine 2a (1.5–2 equiv.) was added to a CH2Cl2 solution of 1 and tetrabutylammonium acetate (B2 equiv.) at room temperature, induced CD signals at wavelengths ranging from 300 nm to 460 nm appeared as a result of the formation of 3a. More specifically, addition of (1R,2R)-2a gave strong excitoncoupled CD signals with positive Cotton effects at 328, 390, and 421 nm and a negative Cotton effect at 363 nm. The CD spectrum was completely inverted when the enantiomer (1S,2S)-2a was used. The structure of imine macrocycle (R,R)-3a, derived from (1R,2R)-2a, was confirmed by single crystal X-ray analysis (Fig. 2). (R,R)-3a is helically twisted with the right-handed (P) orientation, as anticipated by the exciton chirality rule1 based on the CD spectrum showing positive Cotton effects at longer wavelengths. The dihedral angle between two indolocarbazole planes is approximately 221. The acetate ion is coordinated to the internal cavity by four hydrogen bonds; both N O distances are 2.85 Å with two NHs (one of each indolocarbazole) on the butadiynyl side, while they are 3.03 and 3.19 Å with two NHs on the methoxyphenyl side. The condensation reaction between 1 and ethane-1,2-diamine (2b) in the presence of acetate yielded a CD-inactive, racemic mixture of imine macrocycle 3b (Fig. 3a). If a chiral carboxylate is instead used for the reaction, two helical isomers may be formed in an unequal ratio. To test this hypothesis, the same reaction This journal is
c
The Royal Society of Chemistry 2013
Fig. 3 (a) CD spectra (5.0 10 5 M in CH2Cl2, 25 1C) of imine macrocycle 3b upon hydrogen bonding with various anionic N-Boc amino acids. (b) CD spectra obtained from different ratios of anionic D-Ala and L-Ala, and (c) plots of CD spectral intensities in (b) against ee’s of Ala at four different wavelengths.
was conducted in the presence of chiral N-protected a-aminocarboxylates. As a representative example, when anionic N-Boc-alanine (Ala) was used, the imine macrocycle 3b exhibited strong CD signals with first positive Cotton effects from D-Ala but inverted negative effects from L-Ala. When a mixture of D- and L-Ala was used for the reaction, the intensity of CD spectra was linearly proportional to the enantiomeric excess (ee) of the mixture at any wavelength (R2 > 0.99) (Fig. 3b and c). It should be emphasized that the amino acids examined here all exhibit the same trend of CD spectra, that is, first positive Cotton effects from D-amino acids and negative effects from L-amino acids (Fig. 3a; Fig. S6 and Table S1, ESI†). It is also worth mentioning that identical patterns of CD spectra are observed regardless of the kind of protective groups, N-acetyl (Ac) and N-carboxybenzyl (Cbz) protected amino acids (Table S1, Fig. S7 and S8, ESI†). These results demonstrate that imine macrocycle 3b can be used as a stereodynamic probe to determine the absolute configuration and ee’s of a-aminocarboxylates. Chem. Commun., 2013, 49, 11412--11414
11413
View Article Online
ChemComm
Communication
Published on 29 October 2013. Downloaded by University of Pittsburgh on 29/10/2014 12:13:24.
2 Fig. 4 Schematic representation of two binding modes of N-protected-D-aminocarboxylates to the (a) P- and (b) M-conformers of 3b. In the latter, there exists steric strain between the side chain (yellow sphere) of an amino acid and the butadiynyl linker of 3b.
To understand the binding mode, computer modelling studies (MacroModel 9.1,10 gas phase) were carried out with the complexes of 3b with N-acylaminocarboxylates (Fig. 4 and Fig. S9, ESI†). In an energy-minimized structure, the acylamino NH proton is nearly in parallel with the carboxyl group hydrogen bonded to four indolocarbazole NH protons, and it is therefore directed toward the lower one of the two indolocarbazoles. In addition, methoxy substituents in the phenyl rings force the carboxylate plane tilted by approximately 201 to the butadiynyl side as can be seen from the X-ray crystal structure shown in Fig. 2. Consequently, the side chain of amino acids, bulkier than a-hydrogen, prefers to locate away from the butadiynyl linker to minimize otherwise severe steric strain. This explains why P-helices are energetically more stable than M-helices in the complexes with D-amino acids, which agrees well with the observed Cotton effects in the CD spectra. In conclusion, simple mixing of a precursor with a dialdehyde, a diamine and a carboxylate leads to the in situ formation of a helically twisted imine macrocycle exhibiting strong CD signals. The helical orientation of the imine macrocycle faithfully depends on the chirality of carboxylates coordinated to the internal cavity by hydrogen bonds, which allows us to conveniently determine the absolute stereochemistries and ee’s of carboxylates. This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (2013R1A2A2A05005796). We thank Dr J.-m. Suk and M. J. Kim for participating in this project at an early stage. M.J.K. and Y.R.C. acknowledge the fellowship of the BK 21-plus program from the Ministry of Education and Human Resources Development.
Notes and references 1 (a) N. Harada and K. Nakanishi, Circular Dichroic Spectroscopy: Exciton Coupling in Organic Stereochemistry, University Science Books, Mill Valley, CA, USA, 1983; (b) R. V. Person, K. Monde, H.-U. Humpf, N. Berova and K. Nakanishi, Chirality, 1995, 7, 128;
11414
Chem. Commun., 2013, 49, 11412--11414
3
4
5
6
7
8 9 10
(c) N. Berova, L. Di Bari and G. Pescitelli, Chem. Soc. Rev., 2007, 36, 914; (d) G. Pescitelli, L. Di Bari and N. Berova, Chem. Soc. Rev., 2011, 40, 4603; (e) S. G. Telfer, T. M. McLean and M. R. Waterland, Dalton Trans., 2011, 40, 3097; ( f ) J. Jung, J. Jo, M. Laskar and D. Lee, Chem.–Eur. J., 2013, 19, 5156; ( g) C. Wolf and K. Bentley, Chem. Soc. Rev., 2013, 42, 5408. (a) X. Huang, N. Fujioka, G. Pescitelli, F. E. Koehn, R. T. Williamson, K. Nakanishi and N. Berova, J. Am. Chem. Soc., 2002, 124, 10320; ´n, N. Nesnas, Y.-Q. Li, X. Huang, K. Nakanishi and (b) T. Kurta N. Berova, J. Am. Chem. Soc., 2001, 123, 5962; (c) V. V. Borovkov, G. A. Hembury and Y. Inoue, Acc. Chem. Res., 2004, 37, 449; (d) X. Li, M. Tanasova, C. Vasileiou and B. Borhan, J. Am. Chem. Soc., 2008, 130, 1885; (e) V. Borovkov, Symmetry, 2010, 2, 184; ( f ) X. Li, C. E. Burrell, R. J. Staples and B. Borhan, J. Am. Chem. Soc., 2012, 134, 9026. (a) L. You, J. S. Berman and E. V. Anslyn, Nat. Chem., 2011, 3, 943; (b) L. A. Joyce, M. S. Maynor, J. M. Dragna, G. M. da Cruz, V. M. Lynch, J. W. Canary and E. V. Anslyn, J. Am. Chem. Soc., 2011, 133, 13746; (c) J. M. Dragna, G. Pescitelli, L. Tran, V. M. Lynch, E. V. Anslyn and L. Di Bari, J. Am. Chem. Soc., 2012, 134, 4398; (d) L. You, G. Pescitelli, E. V. Anslyn and L. Di Bari, J. Am. Chem. Soc., 2012, 134, 7117; (e) L. You, J. S. Berman, A. Lucksanawichien and E. V. Anslyn, J. Am. Chem. Soc., 2012, 134, 7126. (a) D. P. Iwaniuk and C. Wolf, J. Am. Chem. Soc., 2011, 133, 2414; (b) D. P. Iwaniuk and C. Wolf, Org. Lett., 2011, 13, 2602; (c) D. P. Iwaniuk, K. W. Bentley and C. Wolf, Chirality, 2012, 24, 584; (d) D. P. Iwaniuk and C. Wolf, Chem. Commun., 2012, 48, 11226; (e) N. Fuentes, A. Martin-Lasanta, L. A. de Cienfuegos, R. Robles, ´ndez, D. Choquesillo-Lazarte, J. M. Garcı´a-Ruiz, L. Martı´nez-Ferna ´rdenas, M. C. Carren ˜o I. Corral, M. Ribagorda, A. J. Mota, D. J. Ca and J. M. Cuerva, Angew. Chem., Int. Ed., 2012, 51, 13036. (a) S. Superchi, R. Bisaccia, D. Casarini, A. Laurita and C. Rosini, J. Am. Chem. Soc., 2006, 128, 6893; (b) L. Dutot, K. Wright, A. Gaucher, M. Wakselman, J.-P. Mazaleyrat, M. De Zotti, C. Peggion, F. Formaggio and C. Toniolo, J. Am. Chem. Soc., 2008, 130, 5986; (c) H. Kim, S. M. So, C. P.-H. Yen, E. Vinhato, A. J. Lough, J.-I. Hong, H.-J. Kim and J. Chin, Angew. Chem., Int. Ed., 2008, 47, 8657; (d) M. W. Ghosn and C. Wolf, ´, A. P. H. J. Schenning J. Am. Chem. Soc., 2009, 131, 16360; (e) F. Riobe and D. B. Amabilino, Org. Biomol. Chem., 2012, 10, 9152; ( f ) H. Yoon, C.-H. Lee and W.-D. Jang, Chem.–Eur. J., 2012, 18, 12479; ( g) S. Kuwahara, R. Chamura, S. Tsuchiya, M. Ikeda and Y. Habata, Chem. Commun., 2013, 49, 2186. (a) K.-J. Chang, D. Moon, M. S. Lah and K.-S. Jeong, Angew. Chem., Int. Ed., 2005, 44, 7926; (b) P. A. Gale, Chem. Commun., 2008, 4525; (c) H. Juwarker, J.-m. Suk and K.-S. Jeong, Top. Heterocycl. Chem., 2010, 24, 177. (a) J.-m. Suk and K.-S. Jeong, J. Am. Chem. Soc., 2008, 130, 11868; (b) J.-i. Kim, H. Juwarker, X. Liu, M. S. Lah and K.-S. Jeong, Chem. Commun., 2010, 46, 764; (c) J.-m. Suk, D. A Kim and K.-S. Jeong, Org. Lett., 2012, 14, 5018. J.-m. Suk, V. R. Naidu, X. Liu, M. S. Lah and K.-S. Jeong, J. Am. Chem. Soc., 2011, 133, 13938. For a review of dynamic imine chemistry, see: M. E. Belowich and J. F. Stoddart, Chem. Soc. Rev., 2012, 41, 2003. (a) F. Mohamadi, N. G. J. Richards, W. C. Guida, R. Liskamp, M. Lipton, C. Caufield, G. Chang, T. Hendrickson and W. C. Still, J. Comput. Chem., 1990, 11, 440; (b) T. A. Halgren, J. Comput. Chem., 1996, ¨dinger, LLC, New York, NY, 17, 490; (c) MacroModel, version 9.1, Schro 2005, The energy-minimized structure was generated with MMFF94 force field via Monte Carlo conformational search (3000 times).
This journal is
c
The Royal Society of Chemistry 2013
Published on 29 October 2013. Downloaded by University of Pittsburgh on 29/10/2014 12:13:24.
COMMUNICATION
Cite this: Chem. Commun., 2013, 49, 11412 Received 4th September 2013, Accepted 15th October 2013 DOI: 10.1039/c3cc46754f
View Journal | View Issue
A helically twisted imine macrocycle that allows for determining the absolute configuration of a-amino carboxylates† Min Jun Kim, Ye Rin Choi, Hae-Geun Jeon, Philjae Kang, Moon-Gun Choi and Kyu-Sung Jeong*
www.rsc.org/chemcomm
Binding of a-amino carboxylates to a helically twisted imine macrocycle based on the indolocarbazole scaffold gives rise to characteristic circular dichroism spectra, and the patterns of the Cotton effects are consistent with the absolute configuration of a-amino carboxylates.
Circular dichroism (CD) spectroscopy is a convenient and powerful technique to investigate the chirality of chemical species, including the absolute configuration of stereocenters, the screw sense of helically twisted species, enantiomeric excesses (ee’s), and stereodynamic conformational changes. For this purpose, exciton coupled circular dichroism (ECCD) has been widely implemented for synthetic molecules that possess two or more interacting chromophores oriented in a twisted array.1 Several molecular probes for chirality sensing have been described such as bisporphyrins,2 triaryl propellers,3 arylethynyl foldamers,4 etc.5 Indolocarbazoles are a class of fully conjugated aromatic heterocycles that show strong absorption in the UV-visible region. They have two indole-type NH protons which are able to form strong hydrogen bonds and have been utilized as useful building blocks for synthetic anion receptors.6 Previously, we demonstrated that indolocarbazole foldamers could bind anions with high affinity and selectivity and fold to form helical conformations in solution and in the solid state.7 It was also shown that the helical orientation of an indolocarbazole dimer with chiral residues could be reversibly and completely inverted by anion stimulation, thus functioning as a chiroptical molecular switch.8 Herein, we extend our work to develop a stereodynamic probe that allows for determining the absolute stereochemistries and ee’s of a-aminocarboxylates based on the CD signals. The chirality sensing is ascribed to the helically twisted nature of imine macrocycles 3, and the helical bias is induced by hydrogen bonding of chiral carboxylates to the internal cavity of 3b. Department of Chemistry, Yonsei University, Seoul 120-749, Korea. E-mail: [email protected]; Fax: +82-2-364-7050; Tel: +82-2-2123-2643 † Electronic supplementary information (ESI) available: Characterization data of the new compound, NMR studies, circular dichroism studies, computer modeling, and X-ray crystallographic data. CCDC 951760. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c3cc46754f
11412
Chem. Commun., 2013, 49, 11412--11414
Compound 1 consists of two indolocarbazole chromophores connected through a butadiynyl spacer and two benzaldehyde units at the ends (Scheme 1). In particular, ortho-ethynylbenzaldehyde was chosen to form imine macrocycles with 1,2-diamines.9 The methoxy substituents help increase the solubility in organic solvents. Synthesis of 1 is straightforward and details are summarized in the ESI.† The formation of imine macrocycle 3a between 1 (1 mM) and cyclohexane-(1S,2S)-diamines(2a) (B2 equiv.) was first examined in CD2Cl2 at room temperature by 1H NMR spectroscopy (Fig. 1a). As a template, acetate was used because the hydrogen bonding between 1 and the acetate ion leads to the helical folding of 1. Consequently, the two aldehyde groups are brought in close proximity facilitating formation of imine macrocycle 3a.
Scheme 1 Molecular structures of compound 1, 1,2-diamines 2a and 2b, and imine macrocycles 3a and 3b.
This journal is
c
The Royal Society of Chemistry 2013
View Article Online
Published on 29 October 2013. Downloaded by University of Pittsburgh on 29/10/2014 12:13:24.
Communication
ChemComm
Fig. 2 Two views of the crystal structure of (R,R)-3a complexed with tetrabutylammonium acetate. In the crystal, 3a has P-helix, and the hydrogen bond distances of N3 O97, N23 O98, N6 O97 and N26 O98 are 3.19, 3.03, 2.85 and 2.85 Å, respectively. Countercations and hydrogen atoms except NH protons have been omitted for clarity.
Fig. 1 (a) Partial 1H NMR spectra (400 MHz, CD2Cl2, 25 1C) for the formation of 3a between 1 and (1S,2S)-2a in the presence of tetrabutylammonium acetate. (b) CD spectra (5.0 10 5 M in CH2Cl2, 25 1C) of 3a derived from cyclohexane(1R,2R)-diamine (blue) and its enantiomer (red).
The reaction was completed within 30 min in the presence of tetrabutylammonium acetate (2 equiv.), affording only one set of 1H NMR signals corresponding to the molecular structure of 3a. However, the reaction was complicated in the absence of the acetate ion possibly due to the formation of the 1 : 2 (1/diamine) condensation product and higher oligomers (Fig. S1, ESI†). Moreover, the reaction was significantly slower, having not completed after several hours, which implies that the acetate ion acts as a template as well as facilitates the formation of imine macrocycle 3a. The formation of 3a was also investigated by CD spectroscopy (Fig. 1b). When diamine 2a (1.5–2 equiv.) was added to a CH2Cl2 solution of 1 and tetrabutylammonium acetate (B2 equiv.) at room temperature, induced CD signals at wavelengths ranging from 300 nm to 460 nm appeared as a result of the formation of 3a. More specifically, addition of (1R,2R)-2a gave strong excitoncoupled CD signals with positive Cotton effects at 328, 390, and 421 nm and a negative Cotton effect at 363 nm. The CD spectrum was completely inverted when the enantiomer (1S,2S)-2a was used. The structure of imine macrocycle (R,R)-3a, derived from (1R,2R)-2a, was confirmed by single crystal X-ray analysis (Fig. 2). (R,R)-3a is helically twisted with the right-handed (P) orientation, as anticipated by the exciton chirality rule1 based on the CD spectrum showing positive Cotton effects at longer wavelengths. The dihedral angle between two indolocarbazole planes is approximately 221. The acetate ion is coordinated to the internal cavity by four hydrogen bonds; both N O distances are 2.85 Å with two NHs (one of each indolocarbazole) on the butadiynyl side, while they are 3.03 and 3.19 Å with two NHs on the methoxyphenyl side. The condensation reaction between 1 and ethane-1,2-diamine (2b) in the presence of acetate yielded a CD-inactive, racemic mixture of imine macrocycle 3b (Fig. 3a). If a chiral carboxylate is instead used for the reaction, two helical isomers may be formed in an unequal ratio. To test this hypothesis, the same reaction This journal is
c
The Royal Society of Chemistry 2013
Fig. 3 (a) CD spectra (5.0 10 5 M in CH2Cl2, 25 1C) of imine macrocycle 3b upon hydrogen bonding with various anionic N-Boc amino acids. (b) CD spectra obtained from different ratios of anionic D-Ala and L-Ala, and (c) plots of CD spectral intensities in (b) against ee’s of Ala at four different wavelengths.
was conducted in the presence of chiral N-protected a-aminocarboxylates. As a representative example, when anionic N-Boc-alanine (Ala) was used, the imine macrocycle 3b exhibited strong CD signals with first positive Cotton effects from D-Ala but inverted negative effects from L-Ala. When a mixture of D- and L-Ala was used for the reaction, the intensity of CD spectra was linearly proportional to the enantiomeric excess (ee) of the mixture at any wavelength (R2 > 0.99) (Fig. 3b and c). It should be emphasized that the amino acids examined here all exhibit the same trend of CD spectra, that is, first positive Cotton effects from D-amino acids and negative effects from L-amino acids (Fig. 3a; Fig. S6 and Table S1, ESI†). It is also worth mentioning that identical patterns of CD spectra are observed regardless of the kind of protective groups, N-acetyl (Ac) and N-carboxybenzyl (Cbz) protected amino acids (Table S1, Fig. S7 and S8, ESI†). These results demonstrate that imine macrocycle 3b can be used as a stereodynamic probe to determine the absolute configuration and ee’s of a-aminocarboxylates. Chem. Commun., 2013, 49, 11412--11414
11413
View Article Online
ChemComm
Communication
Published on 29 October 2013. Downloaded by University of Pittsburgh on 29/10/2014 12:13:24.
2 Fig. 4 Schematic representation of two binding modes of N-protected-D-aminocarboxylates to the (a) P- and (b) M-conformers of 3b. In the latter, there exists steric strain between the side chain (yellow sphere) of an amino acid and the butadiynyl linker of 3b.
To understand the binding mode, computer modelling studies (MacroModel 9.1,10 gas phase) were carried out with the complexes of 3b with N-acylaminocarboxylates (Fig. 4 and Fig. S9, ESI†). In an energy-minimized structure, the acylamino NH proton is nearly in parallel with the carboxyl group hydrogen bonded to four indolocarbazole NH protons, and it is therefore directed toward the lower one of the two indolocarbazoles. In addition, methoxy substituents in the phenyl rings force the carboxylate plane tilted by approximately 201 to the butadiynyl side as can be seen from the X-ray crystal structure shown in Fig. 2. Consequently, the side chain of amino acids, bulkier than a-hydrogen, prefers to locate away from the butadiynyl linker to minimize otherwise severe steric strain. This explains why P-helices are energetically more stable than M-helices in the complexes with D-amino acids, which agrees well with the observed Cotton effects in the CD spectra. In conclusion, simple mixing of a precursor with a dialdehyde, a diamine and a carboxylate leads to the in situ formation of a helically twisted imine macrocycle exhibiting strong CD signals. The helical orientation of the imine macrocycle faithfully depends on the chirality of carboxylates coordinated to the internal cavity by hydrogen bonds, which allows us to conveniently determine the absolute stereochemistries and ee’s of carboxylates. This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (2013R1A2A2A05005796). We thank Dr J.-m. Suk and M. J. Kim for participating in this project at an early stage. M.J.K. and Y.R.C. acknowledge the fellowship of the BK 21-plus program from the Ministry of Education and Human Resources Development.
Notes and references 1 (a) N. Harada and K. Nakanishi, Circular Dichroic Spectroscopy: Exciton Coupling in Organic Stereochemistry, University Science Books, Mill Valley, CA, USA, 1983; (b) R. V. Person, K. Monde, H.-U. Humpf, N. Berova and K. Nakanishi, Chirality, 1995, 7, 128;
11414
Chem. Commun., 2013, 49, 11412--11414
3
4
5
6
7
8 9 10
(c) N. Berova, L. Di Bari and G. Pescitelli, Chem. Soc. Rev., 2007, 36, 914; (d) G. Pescitelli, L. Di Bari and N. Berova, Chem. Soc. Rev., 2011, 40, 4603; (e) S. G. Telfer, T. M. McLean and M. R. Waterland, Dalton Trans., 2011, 40, 3097; ( f ) J. Jung, J. Jo, M. Laskar and D. Lee, Chem.–Eur. J., 2013, 19, 5156; ( g) C. Wolf and K. Bentley, Chem. Soc. Rev., 2013, 42, 5408. (a) X. Huang, N. Fujioka, G. Pescitelli, F. E. Koehn, R. T. Williamson, K. Nakanishi and N. Berova, J. Am. Chem. Soc., 2002, 124, 10320; ´n, N. Nesnas, Y.-Q. Li, X. Huang, K. Nakanishi and (b) T. Kurta N. Berova, J. Am. Chem. Soc., 2001, 123, 5962; (c) V. V. Borovkov, G. A. Hembury and Y. Inoue, Acc. Chem. Res., 2004, 37, 449; (d) X. Li, M. Tanasova, C. Vasileiou and B. Borhan, J. Am. Chem. Soc., 2008, 130, 1885; (e) V. Borovkov, Symmetry, 2010, 2, 184; ( f ) X. Li, C. E. Burrell, R. J. Staples and B. Borhan, J. Am. Chem. Soc., 2012, 134, 9026. (a) L. You, J. S. Berman and E. V. Anslyn, Nat. Chem., 2011, 3, 943; (b) L. A. Joyce, M. S. Maynor, J. M. Dragna, G. M. da Cruz, V. M. Lynch, J. W. Canary and E. V. Anslyn, J. Am. Chem. Soc., 2011, 133, 13746; (c) J. M. Dragna, G. Pescitelli, L. Tran, V. M. Lynch, E. V. Anslyn and L. Di Bari, J. Am. Chem. Soc., 2012, 134, 4398; (d) L. You, G. Pescitelli, E. V. Anslyn and L. Di Bari, J. Am. Chem. Soc., 2012, 134, 7117; (e) L. You, J. S. Berman, A. Lucksanawichien and E. V. Anslyn, J. Am. Chem. Soc., 2012, 134, 7126. (a) D. P. Iwaniuk and C. Wolf, J. Am. Chem. Soc., 2011, 133, 2414; (b) D. P. Iwaniuk and C. Wolf, Org. Lett., 2011, 13, 2602; (c) D. P. Iwaniuk, K. W. Bentley and C. Wolf, Chirality, 2012, 24, 584; (d) D. P. Iwaniuk and C. Wolf, Chem. Commun., 2012, 48, 11226; (e) N. Fuentes, A. Martin-Lasanta, L. A. de Cienfuegos, R. Robles, ´ndez, D. Choquesillo-Lazarte, J. M. Garcı´a-Ruiz, L. Martı´nez-Ferna ´rdenas, M. C. Carren ˜o I. Corral, M. Ribagorda, A. J. Mota, D. J. Ca and J. M. Cuerva, Angew. Chem., Int. Ed., 2012, 51, 13036. (a) S. Superchi, R. Bisaccia, D. Casarini, A. Laurita and C. Rosini, J. Am. Chem. Soc., 2006, 128, 6893; (b) L. Dutot, K. Wright, A. Gaucher, M. Wakselman, J.-P. Mazaleyrat, M. De Zotti, C. Peggion, F. Formaggio and C. Toniolo, J. Am. Chem. Soc., 2008, 130, 5986; (c) H. Kim, S. M. So, C. P.-H. Yen, E. Vinhato, A. J. Lough, J.-I. Hong, H.-J. Kim and J. Chin, Angew. Chem., Int. Ed., 2008, 47, 8657; (d) M. W. Ghosn and C. Wolf, ´, A. P. H. J. Schenning J. Am. Chem. Soc., 2009, 131, 16360; (e) F. Riobe and D. B. Amabilino, Org. Biomol. Chem., 2012, 10, 9152; ( f ) H. Yoon, C.-H. Lee and W.-D. Jang, Chem.–Eur. J., 2012, 18, 12479; ( g) S. Kuwahara, R. Chamura, S. Tsuchiya, M. Ikeda and Y. Habata, Chem. Commun., 2013, 49, 2186. (a) K.-J. Chang, D. Moon, M. S. Lah and K.-S. Jeong, Angew. Chem., Int. Ed., 2005, 44, 7926; (b) P. A. Gale, Chem. Commun., 2008, 4525; (c) H. Juwarker, J.-m. Suk and K.-S. Jeong, Top. Heterocycl. Chem., 2010, 24, 177. (a) J.-m. Suk and K.-S. Jeong, J. Am. Chem. Soc., 2008, 130, 11868; (b) J.-i. Kim, H. Juwarker, X. Liu, M. S. Lah and K.-S. Jeong, Chem. Commun., 2010, 46, 764; (c) J.-m. Suk, D. A Kim and K.-S. Jeong, Org. Lett., 2012, 14, 5018. J.-m. Suk, V. R. Naidu, X. Liu, M. S. Lah and K.-S. Jeong, J. Am. Chem. Soc., 2011, 133, 13938. For a review of dynamic imine chemistry, see: M. E. Belowich and J. F. Stoddart, Chem. Soc. Rev., 2012, 41, 2003. (a) F. Mohamadi, N. G. J. Richards, W. C. Guida, R. Liskamp, M. Lipton, C. Caufield, G. Chang, T. Hendrickson and W. C. Still, J. Comput. Chem., 1990, 11, 440; (b) T. A. Halgren, J. Comput. Chem., 1996, ¨dinger, LLC, New York, NY, 17, 490; (c) MacroModel, version 9.1, Schro 2005, The energy-minimized structure was generated with MMFF94 force field via Monte Carlo conformational search (3000 times).
This journal is
c
The Royal Society of Chemistry 2013
