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Synthesis and resolution of a new thiahexahelicene
Tetrahedron Letters 53 (2012) 5824–5827
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Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
Synthesis and resolution of a new thiahexahelicene Souad Moussa, Faouzi Aloui, Béchir Ben Hassine ⇑ Laboratoire de Synthèse Organique Asymétrique et Catalyse Homogène (O1UR1201), Faculté des Sciences, Avenue de l’environnement, 5019 Monastir, Tunisia
a r t i c l e
i n f o
Article history: Received 19 April 2012 Revised 18 May 2012 Accepted 18 July 2012 Available online 27 July 2012 Keywords: Helicenes Heck coupling Photocyclization Fused-rings
a b s t r a c t A new thiahexahelicene bearing a methoxy group, at a selected position on the terminal aromatic ring, was prepared in a good yield through Heck coupling and photocyclization reactions. The X-ray crystal structure of the product indicates that its conformation closely resembles that of the unsubstituted hexahelicene, whose idealized symmetry is C2. Both enantiomers of the new helically chiral hexacyclic system have been successfully separated using (R)-2-phthalimidopropanoic acid chloride as a chiral resolving agent. Ó 2012 Elsevier Ltd. All rights reserved.
Helicenes are unique, three-dimensional aromatic systems that are inherently chiral, thermally stable, and perfectly p-conjugated materials.1 They exhibit an attractive molecular structure and, accordingly, promising chemical and physical properties.2,3 However, helicenes were considered to be textbook examples of small helices rather than practically useful entities for most of the fivedecade lifetime of helicene chemistry.4 The main reasons behind this were the difficult preparation of helicenes and the absence of a more general synthetic methodology to obtain individual enantiomers on preparative scale. However, interest in heterohelicenes has not been merely speculative, but also applicative because these molecules have a nicely delocalized p-electron system with a high thermal stability which allow them to exhibit interesting opto- and photo-electronic properties.5–11 In this context, the development of new heterohelicenes and further study of the underlying structure–property relationships represented an interesting challenge. Due to the small number of optically active [6]helicenes, we envisioned to design and synthesize a thiahexahelicene with a methoxy group at a selected position on the terminal aromatic ring. Our synthetic approach is based on the utilization of the tetracyclic ring system 112 as a suitable key building block to provide the helicene-precursor 2, which is then easily converted into the helically-chiral thiahexacyclic system 3 by oxidative photocyclization. The methoxy group in this chiral compound serves as an appropriate functional group for increasing the solubility of helicene in organic solvents. The benzo[c]phenanthrene-like system 1 and 4-methoxystyrene undergo a Mizoroki–Heck coupling using 1% of Hermann’s
⇑ Corresponding author. Tel.: +216 73500279; fax: +216 73500278. E-mail address: [email protected] (B.B. Hassine). 0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tetlet.2012.07.076
catalyst, sodium acetate as the base, and N,N-dimethylacetamide as the solvent according to Scheme 1. The mixture was heated at 140 °C for about 48 h to afford the diarylethene 2 in 78% yield. The coupled product was assumed to have E-stereochemistry at the double bond, based on a 1H NMR study.13 The resulting diarylethene 2 was then subjected to photocyclization in toluene in the presence of a stoichiometric amount of I2 as the oxidizing agent and an excess of propylene oxide.14 The photolysis was performed on 150 mg scale, per run, in a 1 L reactor for about 3 h, to give the expected 14-methoxy-5-thiahexahelicene 3 in 75% yield (Scheme 1).15 No other regioisomer was isolated from the reaction mixture indicating that ring-closure of diarylethene 2 had occurred at the peri position of the tetracyclic moiety. Treatment of compound 3 with boron tribromide solution in dichloromethane provided the corresponding 14-hydroxy-5-thiahexahelicene 4 in 95% yield (Scheme 1). Crystallization of 14-methoxy-5-thiahexahelicene 3 from a dichloromethane/hexane mixture gave pale yellow crystals (Fig. 1).15 This compound, which is stable in air and light, did not undergo spontaneous resolution, though its space group is P21. Some of the inner and outer bond lengths are given in Table 1. It was found that the thiophene ring of the helicene molecule affected appreciably the outer bond lengths; it reduced the lengths of the C15–C16, C17–C18, and C23–C24 bonds, but increased the lengths of the C2–C3 and C9–C10 bonds with respect to the bond length in benzene (1.39 Å). The torsion angles at the inner helical rim were also a convenient measure of the helicity (Table 2). The torsion angles represented by C5–C6–C7–C12 and C12–C13–C20–C21, formed by the inner helix, showed unequal, but relatively small angles of 13° and 5.8°, respectively. The deformation of the dihedral angles of the inner helix bonds of 3 was mainly attributed to the pentacyclic thiophene ring in comparison with those of [6]helicene.16
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S. Moussa et al. / Tetrahedron Letters 53 (2012) 5824–5827
S S OCH3 +
1%[Pd], NaOAc DMA, 140 °C, 48 h 78%
Br 1
2 OCH3
S
S
OH
OCH3 BBr3, CH2Cl2
hν, toluene propylene oxide, I2
95%
75% 3
4
Scheme 1. Synthesis of 14-hydroxy-5-thiahexahelicene 4.
Table 2 Torsion angles of (±)-3 and hexahelicene Compound
Torsion angle
3 Hexahelicene a u1 = C5–C6–C7–C12; u4 = C7–C12–C13–C20.
a
(°)
u1
u2
u3
u4
13 11.2
25 30.0
5.8 15.2
24 30.3
u2 = C6–C7–C12–C13;
u3 = C12–C13–C20–C21;
3 4
Absorbance (a.u)
0.8
0.4
0.0 Figure 1. Crystal structure of 14-methoxy-5-thiahexahelicene 3: ORTEP drawing.
250
300
350
400
450
Wavelength (nm) Figure 2. UV/Vis absorption spectra of compounds 3 and 4 obtained from dilute CHCl3 solutions. Table 1 Selected inner and outer bond lengths (Å) in (±)-3 Table 3 Physical properties of the helically-chiral compounds 3 and 4
Inner C–C bond lengths C5–C6 C6–C7 C7–C12 C12–C13 C13–C20 C20–C21
1.36 1.44 1.43 1.48 1.55 1.39
Outer C–C bond lengths C2–C3 C9–C10 C15–C16 C17–C18 C23–C24
1.45 1.72 1.27 1.31 1.17
Compound
kAbs max (nm)
EOpt (eV)
3 4
315 305
2.98 2.92
The optical properties of the racemic thiahexahelicene derivatives 3 and 4 were investigated using UV/Vis absorption studies on dilute chloroform solutions (Fig. 2).15 The UV/Vis spectra of the compounds exhibited a strong absorption in the region of 250–425 nm. The absorption of hexahelicene 4 in the high energy
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S. Moussa et al. / Tetrahedron Letters 53 (2012) 5824–5827
S
OH +
O
O
N
CH3
Cl O (R)-5
(P,M)-4
1) Et3N, CH2Cl2 0°C 2) SiO2 column 28% S
33% O
CH3
S
N
O
N
O
O O
(P,R)-6
O
CH3
O O
(M,R)-6 KOH, EtOH 90%
KOH, EtOH 90% S
S OH
(P)-(+)-4
OH
(M)-(-)-4
Scheme 2. Enantiomeric resolution of the helically chiral alcohol 4.
region was well-structured containing seven prominent bands at 250, 293, 306, 331, 349, 375, and 396. These absorption bands were associated with p–p⁄ and n–p⁄ electronic transitions,17 and were similar to the characteristic vibration patterns of other helicene derivatives.18 No broad absorption band in the low energy region was observed. The results summarized in Table 3 show absorption maxima at 315 nm and 305 nm for 3 and 4, respectively. The optical energy band gap of the hexahelicene 3 was calculated as 2.92 eV from the onset of the absorption around 415 nm. The UV absorption results show that the optical band gap of these new helicene derivatives was lower than 3.5 eV. This result might be due to the formation of aggregation due to p–p⁄ stacking, or intermolecular interactions caused by their nonplanar structures. Finally, having obtained the new helical alcohol 4, we next investigated its possible enantiomeric resolution. To perform this resolution, we used (R)-2-phthalimidopropanoic acid chloride 5 as a chiral resolving agent to convert the racemic alcohols into diastereoisomers which could be separated by crystallization or by chromatography. Thus, treatment of racemic alcohol 4 with (R)2-phthalimidopropanoic acid chloride 5, in the presence of triethylamine as a base and dichloromethane as the solvent at room temperature, led to a 1:1 mixture of two diastereomeric helicene esters (M,R)-6 and (P,R)-6 in 87% yield (Scheme 2). The resulting diastereomeric mixture (150 mg) was eluted at room temperature on a SiO2 column with cyclohexane–EtOAc (98:2 up to 70:30) as eluent. The fractions eluted were checked by TLC. The earlier eluting fractions consisted of the diastereomer (M,R)-6, exhibiting a
negative optical rotation, which was obtained in 33% yield (49 mg) with a diastereomeric excess of 79%.19 Later eluting fractions gave the second diastereomer (P,R)-6 in 28% yield (42 mg) with only 70% de.20 The optical purities of both diastereomers were determined by 1H NMR spectroscopy. The specific rotation values obtained for (M,R)-6 and (P,R)-6 were found to be [a]D 1900 (c 0.05, CHCl3) and + 1200 (c 0.05, CHCl3), respectively. The very high specific rotation values are a common feature of helical structures, while the sign of the optical rotation allows reliable assignment of the helical configuration.21,22 Treatment of the resulting optically active diastereomers (M,R)6 and (P,R)-6 with a solution of potassium hydroxide in refluxing ethanol gave the corresponding alcohols (M)-( )-4 and (P)-(+)-4, respectively, in good yields (Scheme 2).23 In summary, we have developed a synthetic approach and have undertaken enantiomeric resolution of the new hydroxyhexahelicene 4. We completed the synthesis of racemic 4 in only four steps with an overall 55% yield. We also demonstrated that (R)-2-phthalimidopropanoic acid chloride 5 was a suitable resolving agent for the helically-chiral alcohol. This helicene could serve as a ligand in asymmetric synthesis or as a building block for supramolecular architectures. Work in this field is currently in progress. Acknowledgments The authors are grateful to Pascal Retailleau for the X-ray analysis and to the DGRS (Direction Générale de la Recherche Scientifique) of the Tunisian Ministry of Higher Education and Scientific Research for financial support.
S. Moussa et al. / Tetrahedron Letters 53 (2012) 5824–5827
Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.tetlet.2012.07. 076. References and notes 1. (a) Urbano, A. Angew. Chem., Int. Ed. 2003, 42, 3986–3989; (b) Katz, T. J. Angew. Chem,. Int. Ed. 2000, 39, 1921–1923; (c) Meurer, K. P.; Vögtle, F. Top. Curr. Chem. 1985, 127, 1–76; (d) Laarhoven, W. H.; Prinsen, W. J. C. Top. Curr. Chem. 1984, 125, 63–130. 2. (a) Xu, Y.; Zhang, Y. X.; Sugiyama, H.; Umano, T.; Osuga, H.; Tanaka, K. J. Am. Chem. Soc. 2004, 126, 6566–6567; (b) Fasel, R.; Parschau, M.; Ernst, K. H. Angew. Chem., Int. Ed. 2003, 42, 5178–5181; (c) Reetz, M. T.; Sostmann, S. Tetrahedron 2001, 57, 2515–2520; (d) Reetz, M. T.; Sostmann, S. J. Organomet. Chem. 2000, 603, 105–109; (e) Weix, D. J.; Dreher, S. D.; Katz, T. J. J. Am. Chem. Soc. 2000, 122, 10027–10032; (f) Verbiest, T.; Van Elshocht, S.; Kauranen, M.; Hellemans, L.; Snauwaert, J.; Nuckolls, C.; Katz, T. J.; Persoons, A. Science 1998, 282, 913–915; (g) Kelly, T. R.; Sestelo, J. P.; Tellitu, I. J. Org. Chem. 1998, 63, 3655–3665; (h) Owens, L.; Thilgen, C.; Diederich, F.; Knobler, C. B. Helv. Chim. Acta 1993, 76, 2757–2774; (i) Ben.Hassine, B.; Gorsane, M.; Pecher, J.; Martin, R. H. Bull. Soc. Chim. Belg. 1986, 95, 547–556. 3. (a) Treboux, G.; Lapstun, P.; Wu, Z. H.; Silverbrook, K. Chem. Phys. Lett. 1999, 301, 493–497; (b) Jalaie, M.; Weatherhead, S.; Lipkowitz, K. B.; Robertson, D. Electron. J. Theor. Chem. 1997, 2, 268–272. 4. (a) Newman, M. S.; Lutz, W. B.; Lednitzer, D. J. Am. Chem. Soc. 1955, 77, 3420– 3421; (b) Newman, M. S.; Lednicer, D. J. Am. Chem. Soc. 1956, 78, 4765–4770. 5. Beljonne, D.; Shuai, Z.; Bredas, J. L.; Kauranen, M.; Verbiest, T.; Persoons, A. J. Chem. Phys. 1998, 108, 1301–1304. 6. Caronna, T.; Sinisi, R.; Catellani, M.; Luzzati, S.; Abbate, S.; Longhi, G. Synth. Met. 2001, 119, 79–80. 7. Sahasithiwat, S.; Mophuang, T.; Menbangpung, L.; Kamtonwong, S.; Sooksimuang, T. Synth. Met. 2010, 160, 1148–1152. 8. Wynberg, H. Acc. Chem. Res. 1971, 4, 65–67. 9. Maiorana, S.; Papagni, A.; Licandro, E.; Annunziata, R.; Parravidino, P.; Perdicchia, D.; Giannini, C.; Bencini, M.; Clays, K.; Persoons, A. Tetrahedron 2003, 59, 6481–6488. 10. Collins, S. K.; Vachon, M. P. Org. Biomol. Chem. 2006, 4, 2518–2524. 11. Tovar, J. D.; Rose, A.; Swager, T. M. J. Am. Chem. Soc. 2002, 124, 7762–7769. 12. Aloui, F.; Moussa, S.; Ben Hassine, B. Tetrahedron Lett. 2011, 52, 572–575. 13. Spectroscopic data for diarylethene 2: colorless solid, showing a violet fluorescence when dissolved in CH2Cl2, Rf = 0.5 (cyclohexane/EtOAc, 98:2); mp = 171–173 °C; 1H NMR (300 MHz, CDCl3): d (ppm): 3.87 (s, 3H, OCH3), 6.96 (d, J = 8.7 Hz, 2H), 7.24–7.31 (m, 2H), 7.50–7.67 (m, 3H), 7.82–7.91 (m, 3 H), 7.94–8.02 (m, 2H), 8.91 (d, J = 8.1 Hz, 2H), 8.95 (s, 1H); 13C NMR (75 MHz, CDCl3): d (ppm): 55.41 (OCH3), 114.26 (2 CH), 120.84 (CH), 122.11 (CH), 122.17 (C), 123.29 (CH), 124.79 (CH), 124.90 (CH), 125.30 (C), 127.12 (CH), 127.61 (CH), 127.98 (2 CH), 128.20 (C), 129.30 (C), 129.79 (CH), 130.13 (CH), 131.07 (C), 139.29 (CH), 123.24 (CH), 136.49 (C), 139,09 (C), 139.61 (C), 159.54 (C–O); ESI-MS: m/z = 366.10 [M]+. 14. Liu, L.; Yang, B.; Katz, T. J.; Poindexter, M. K. J. Org. Chem. 1991, 56, 3769–3775. 15. Spectroscopic data for 14-methoxy-5-thiahexahelicene 3: pale yellow solid; Rf = 0.52 (cyclohexane/EtOAc, 98:2); mp = 218–220 °C; 1H NMR (300 MHz, CDCl3): d (ppm): 2.80 (s, 3H, OCH3), 6.80 (ddd, J1 = 1.2 Hz, J2 = 6.9 Hz, J3 = 8.1 Hz, 1H), 6.87 (d, J = 7.8 Hz, 1H), 7.01 (dd, J1 = 2.4 Hz, J2 = 8.7 Hz, 1H), 7.16–7.24 (m, 2H), 7.78 (d, J = 8.4 Hz, 1H), 7.82–7.86 (m, 3H), 7.91 (d, J = 8.7 Hz, 1H), 7.93 (d, J = 8.1 Hz, 1H), 7.96 (d, J = 8.4 Hz, 1H), 8.02 (d, J = 8.4 Hz, 1H); 13C NMR (75 MHz, CDCl3): d (ppm): 54.63 (OCH3), 109.47 (CH), 118.14 (CH), 121.59 (CH), 122.42 (CH), 123.00 (CH), 124.20 (CH), 125.21 (C), 125.33 (C), 125.87 (CH), 126.65 (CH), 127.01 (C), 127.08 (CH), 127.54 (CH), 127.88 (CH), 128.23 (CH), 129.72 (CH), 131.30 (C), 131.46 (C), 131.84 (C), 133.22 (C), 136.59 (C), 138.51 (C), 139.76 (C), 157.73 (C); HRMS (MALDI-TOF) calcd for C25H16OS
16. 17. 18.
19.
20.
21. 22.
23.
5827
[M]+: 364.09218. Found: 364.09162. Crystal data for compound 3 (C25H16OS) were recorded on a Bruker SMART CCD diffractometer, M = 365.44, monoclinic, space group P21. a = 10.0862(7) Å, b = 6.5339(4) Å, c = 13.6536(10) Å, V = 899.80(11) Å3, Z = 2, qcalcd = 1.345 g/cm3, X-ray source CuKa, k = 1.54187 Å, T = 293(2) K, measured reflections 2974, independent reflections 1707, reflections used 1707, refinement type Fsqd, parameters refined 238, R1 = 0.1536, wR2 = 0.3652. Crystallographic data for the structure have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 851811. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44(0)-1223-336033 or email: [email protected]. Navaza, J.; Tsoucaris, G.; le Bas, G.; Navaza, A.; de Rango, C. Bull. Soc. Chim. Belg. 1979, 88, 863–870. Ogawa, Y.; Toyama, M.; Karikomi, M.; Seki, K.; Hagaa, K.; Uyehara, T. Tetrahedron Lett. 2003, 44, 2167–2170. Bossi, A.; Licandro, E.; Maiorana, S.; Rigamonti, C.; Righetto, S.; Stephenson, G. R.; Spassova, M.; Botek, E.; Champagne, B. J.Phys. Chem. C 2008, 112, 7900– 7907. Spectroscopic data for diastereomer (M,R)-6: yellow solid, 79% de; mp = 156– 158 °C; Rf = 0.32 (cyclohexane/EtOAc, 90:10); [a]D 1900 (c 0.05, CHCl3); 1H NMR (300 MHz, CDCl3): d (ppm): 1.58 (d, J = 4.2 Hz, 3H, CH3), 4.95 (q, J = 5.7 Hz, 1H, CHN), 6.83 (ddd, J1 = 1.2 Hz, J2 = 6.9 Hz, J3 = 8.1 Hz, 1H), 6.86 (d, J = 8.1 Hz, 1H), 7.11 (ddd, J1 = 1.5 Hz, J2 = 6.9 Hz, J3 = 8.1 Hz, 1H), 7.30 (dd, J1 = 2.4 Hz, J 2 = 8.7 Hz, 1H), 7.54 (d, J = 2.1 Hz, 1H), 7.79–7.82 (m, 3H), 7.88–7.94 (m, 3H), 7.97–8.03 (m, 5H), 8.12 (d, J = 8.7 Hz, 1H); 13C NMR (75 MHz, CDCl3): d (ppm): 15.61 (CH3), 47.50 (CHN), 120.62 (CH), 121.02 (CH), 122.23 (CH), 122.50 (C), 123.12 (CH), 123.93 (C), 124.03 (2 CH), 124.99 (C), 125.53 (C), 125.60 (CH), 126.23 (CH), 126.41 (CH), 126.66 (CH), 127.35 (CH), 128.03 (CH), 128.42 (CH), 129.44 (CH), 130.02 (C), 131.16 (C), 131.29 (C), 131.93 (C), 132.19 (CH), 132.89 (C), 134.55 (2 CH), 136.06 (C), 138.42 (C), 140.12 (C), 148.69 (C), 167.37 (2 C–O), 168.43 (CO). Spectroscopic data for diastereomer (P,R)-6: yellow solid, 70% de; mp = 202– 204 °C; Rf = 0.34 (cyclohexane/EtOAc, 90:10); [a]D +1200 (c 0.05, CHCl3); 1H NMR (300 MHz, CDCl3): d (ppm): 1.58 (d, J = 4.2 Hz, 3H, CH3), 4.91 (q, J = 7.2 Hz, 1H, CHN), 6.71 (ddd, J1 = 0.9 Hz, J2 = 6.9 Hz, J3 = 8.1 Hz, 1H), 6.83 (d, J = 8.1 Hz, 1H), 6.95 (ddd, J1 = 1.2 Hz, J1 = 6.9 Hz, J3 = 8.1 Hz, 1H), 7.29 (dd, J1 = 2.1 Hz, J2 = 8.7 Hz, 1H), 7.55 (d, J = 2.1 Hz, 1H), 7.74–7.80 (m, 3H), 7.85–7.93 (m, 3H), 7.96–8.03 (m, 5H), 8.07 (d, J = 8.4 Hz, 1H); 13C NMR (75 MHz, CDCl3): d (ppm): 15.29 (CH3), 47.32 (CHN), 120.10 (CH), 120.31 (CH), 121.75 (CH), 122.15 (CH), 122.63 (CH), 123.58 (2 CH), 124.51 (C), 125.17 (CH), 125.88 (CH), 126.00 (CH), 126.29 (CH), 126.96 (CH), 127.68 (CH), 128.04 (CH), 129.05 (CH), 129.62 (C), 130.49 (C), 130.74 (C), 131.57 (C), 131.97 (C), 132.54 (C), 134.21 (2 CH), 134.62 (C), 135.74 (C), 136.09 (C), 138.36 (C), 139.90 (C), 148.39 (C), 167.12 (2 CO), 168.01 (CO). For an early review, see: Martin, R. H. Angew. Chem., Int. Ed. Engl. 1974, 13, 649– 660. In carbohelicenes known so far, ( )-enantiomers always have the (M) helicity Grimme, S.; Harren, J.; Sobanski, A.; Vögtle, F. Eur. J. Org. Chem. 1998, 1491– 1509. Selected spectral data for (M)-( )-14-hydroxy-5-thiahexahelicene (4): pale yellow solid; mp = 283–285 °C; Rf = 0.23 (cyclohexane/EtOAc 95:5); [a]D 1787 (c 0.08, CHCl3); 1H NMR (300 MHz, CDCl3): d (ppm): 4.51 (s, 1H, OH), 6.80 (ddd, J1 = 1.2 Hz, J2 = 6.9 Hz, J3 = 8.1 Hz, 1H), 6.89 (d, J = 7.8 Hz, 1H), 6.97 (dd, J1 = 2.4 Hz, J2 = 8.7 Hz, 1H), 7.14–7.24 (m, 2H), 7.73 (d, J = 8.4 Hz, 1H), 7.78 (d, J = 8.4 Hz, 1H), 7.81 (d, J = 8.4 Hz, 1H), 7.82–7.86 (m, 2H), 7.90 (d, J = 8.4 Hz, 1H), 7.92 (d, J = 8.4 Hz, 1H), 8.00 (d, J = 8.4 Hz, 1H); 13C NMR (75 MHz, CDCl3): d (ppm): 112.45 (CH), 116.42 (CH), 121.28 (CH), 122.00 (CH), 122.71 (CH), 123.71 (CH), 124.62 (C), 124.84 (C), 125.59 (CH), 126.14 (CH), 126.50 (C), 126.58 (CH), 127.10 (CH), 127.61 (CH), 127.95 (CH), 129.76 (CH), 131.10 (C), 131.36 (C), 131.53 (C), 132.96 (C), 136.04 (C), 138.16 (C), 139.37 (C), 153.87 (C– O); HRMS (MALDI-TOF) calcd for C24H15OS [M+H]+: 351.08436. Found: 351.08312. (P)-(+)-14-hydroxy-5-thiahexahelicene (4): pale yellow solid; mp = 284–286 °C; Rf = 0.23 (cyclohexane/EtOAc 95:5); [a]D +1187 (c 0.07, CHCl3); ESI-MS: m/z = 351 [M+H]+.
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet
Synthesis and resolution of a new thiahexahelicene Souad Moussa, Faouzi Aloui, Béchir Ben Hassine ⇑ Laboratoire de Synthèse Organique Asymétrique et Catalyse Homogène (O1UR1201), Faculté des Sciences, Avenue de l’environnement, 5019 Monastir, Tunisia
a r t i c l e
i n f o
Article history: Received 19 April 2012 Revised 18 May 2012 Accepted 18 July 2012 Available online 27 July 2012 Keywords: Helicenes Heck coupling Photocyclization Fused-rings
a b s t r a c t A new thiahexahelicene bearing a methoxy group, at a selected position on the terminal aromatic ring, was prepared in a good yield through Heck coupling and photocyclization reactions. The X-ray crystal structure of the product indicates that its conformation closely resembles that of the unsubstituted hexahelicene, whose idealized symmetry is C2. Both enantiomers of the new helically chiral hexacyclic system have been successfully separated using (R)-2-phthalimidopropanoic acid chloride as a chiral resolving agent. Ó 2012 Elsevier Ltd. All rights reserved.
Helicenes are unique, three-dimensional aromatic systems that are inherently chiral, thermally stable, and perfectly p-conjugated materials.1 They exhibit an attractive molecular structure and, accordingly, promising chemical and physical properties.2,3 However, helicenes were considered to be textbook examples of small helices rather than practically useful entities for most of the fivedecade lifetime of helicene chemistry.4 The main reasons behind this were the difficult preparation of helicenes and the absence of a more general synthetic methodology to obtain individual enantiomers on preparative scale. However, interest in heterohelicenes has not been merely speculative, but also applicative because these molecules have a nicely delocalized p-electron system with a high thermal stability which allow them to exhibit interesting opto- and photo-electronic properties.5–11 In this context, the development of new heterohelicenes and further study of the underlying structure–property relationships represented an interesting challenge. Due to the small number of optically active [6]helicenes, we envisioned to design and synthesize a thiahexahelicene with a methoxy group at a selected position on the terminal aromatic ring. Our synthetic approach is based on the utilization of the tetracyclic ring system 112 as a suitable key building block to provide the helicene-precursor 2, which is then easily converted into the helically-chiral thiahexacyclic system 3 by oxidative photocyclization. The methoxy group in this chiral compound serves as an appropriate functional group for increasing the solubility of helicene in organic solvents. The benzo[c]phenanthrene-like system 1 and 4-methoxystyrene undergo a Mizoroki–Heck coupling using 1% of Hermann’s
⇑ Corresponding author. Tel.: +216 73500279; fax: +216 73500278. E-mail address: [email protected] (B.B. Hassine). 0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tetlet.2012.07.076
catalyst, sodium acetate as the base, and N,N-dimethylacetamide as the solvent according to Scheme 1. The mixture was heated at 140 °C for about 48 h to afford the diarylethene 2 in 78% yield. The coupled product was assumed to have E-stereochemistry at the double bond, based on a 1H NMR study.13 The resulting diarylethene 2 was then subjected to photocyclization in toluene in the presence of a stoichiometric amount of I2 as the oxidizing agent and an excess of propylene oxide.14 The photolysis was performed on 150 mg scale, per run, in a 1 L reactor for about 3 h, to give the expected 14-methoxy-5-thiahexahelicene 3 in 75% yield (Scheme 1).15 No other regioisomer was isolated from the reaction mixture indicating that ring-closure of diarylethene 2 had occurred at the peri position of the tetracyclic moiety. Treatment of compound 3 with boron tribromide solution in dichloromethane provided the corresponding 14-hydroxy-5-thiahexahelicene 4 in 95% yield (Scheme 1). Crystallization of 14-methoxy-5-thiahexahelicene 3 from a dichloromethane/hexane mixture gave pale yellow crystals (Fig. 1).15 This compound, which is stable in air and light, did not undergo spontaneous resolution, though its space group is P21. Some of the inner and outer bond lengths are given in Table 1. It was found that the thiophene ring of the helicene molecule affected appreciably the outer bond lengths; it reduced the lengths of the C15–C16, C17–C18, and C23–C24 bonds, but increased the lengths of the C2–C3 and C9–C10 bonds with respect to the bond length in benzene (1.39 Å). The torsion angles at the inner helical rim were also a convenient measure of the helicity (Table 2). The torsion angles represented by C5–C6–C7–C12 and C12–C13–C20–C21, formed by the inner helix, showed unequal, but relatively small angles of 13° and 5.8°, respectively. The deformation of the dihedral angles of the inner helix bonds of 3 was mainly attributed to the pentacyclic thiophene ring in comparison with those of [6]helicene.16
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S S OCH3 +
1%[Pd], NaOAc DMA, 140 °C, 48 h 78%
Br 1
2 OCH3
S
S
OH
OCH3 BBr3, CH2Cl2
hν, toluene propylene oxide, I2
95%
75% 3
4
Scheme 1. Synthesis of 14-hydroxy-5-thiahexahelicene 4.
Table 2 Torsion angles of (±)-3 and hexahelicene Compound
Torsion angle
3 Hexahelicene a u1 = C5–C6–C7–C12; u4 = C7–C12–C13–C20.
a
(°)
u1
u2
u3
u4
13 11.2
25 30.0
5.8 15.2
24 30.3
u2 = C6–C7–C12–C13;
u3 = C12–C13–C20–C21;
3 4
Absorbance (a.u)
0.8
0.4
0.0 Figure 1. Crystal structure of 14-methoxy-5-thiahexahelicene 3: ORTEP drawing.
250
300
350
400
450
Wavelength (nm) Figure 2. UV/Vis absorption spectra of compounds 3 and 4 obtained from dilute CHCl3 solutions. Table 1 Selected inner and outer bond lengths (Å) in (±)-3 Table 3 Physical properties of the helically-chiral compounds 3 and 4
Inner C–C bond lengths C5–C6 C6–C7 C7–C12 C12–C13 C13–C20 C20–C21
1.36 1.44 1.43 1.48 1.55 1.39
Outer C–C bond lengths C2–C3 C9–C10 C15–C16 C17–C18 C23–C24
1.45 1.72 1.27 1.31 1.17
Compound
kAbs max (nm)
EOpt (eV)
3 4
315 305
2.98 2.92
The optical properties of the racemic thiahexahelicene derivatives 3 and 4 were investigated using UV/Vis absorption studies on dilute chloroform solutions (Fig. 2).15 The UV/Vis spectra of the compounds exhibited a strong absorption in the region of 250–425 nm. The absorption of hexahelicene 4 in the high energy
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S
OH +
O
O
N
CH3
Cl O (R)-5
(P,M)-4
1) Et3N, CH2Cl2 0°C 2) SiO2 column 28% S
33% O
CH3
S
N
O
N
O
O O
(P,R)-6
O
CH3
O O
(M,R)-6 KOH, EtOH 90%
KOH, EtOH 90% S
S OH
(P)-(+)-4
OH
(M)-(-)-4
Scheme 2. Enantiomeric resolution of the helically chiral alcohol 4.
region was well-structured containing seven prominent bands at 250, 293, 306, 331, 349, 375, and 396. These absorption bands were associated with p–p⁄ and n–p⁄ electronic transitions,17 and were similar to the characteristic vibration patterns of other helicene derivatives.18 No broad absorption band in the low energy region was observed. The results summarized in Table 3 show absorption maxima at 315 nm and 305 nm for 3 and 4, respectively. The optical energy band gap of the hexahelicene 3 was calculated as 2.92 eV from the onset of the absorption around 415 nm. The UV absorption results show that the optical band gap of these new helicene derivatives was lower than 3.5 eV. This result might be due to the formation of aggregation due to p–p⁄ stacking, or intermolecular interactions caused by their nonplanar structures. Finally, having obtained the new helical alcohol 4, we next investigated its possible enantiomeric resolution. To perform this resolution, we used (R)-2-phthalimidopropanoic acid chloride 5 as a chiral resolving agent to convert the racemic alcohols into diastereoisomers which could be separated by crystallization or by chromatography. Thus, treatment of racemic alcohol 4 with (R)2-phthalimidopropanoic acid chloride 5, in the presence of triethylamine as a base and dichloromethane as the solvent at room temperature, led to a 1:1 mixture of two diastereomeric helicene esters (M,R)-6 and (P,R)-6 in 87% yield (Scheme 2). The resulting diastereomeric mixture (150 mg) was eluted at room temperature on a SiO2 column with cyclohexane–EtOAc (98:2 up to 70:30) as eluent. The fractions eluted were checked by TLC. The earlier eluting fractions consisted of the diastereomer (M,R)-6, exhibiting a
negative optical rotation, which was obtained in 33% yield (49 mg) with a diastereomeric excess of 79%.19 Later eluting fractions gave the second diastereomer (P,R)-6 in 28% yield (42 mg) with only 70% de.20 The optical purities of both diastereomers were determined by 1H NMR spectroscopy. The specific rotation values obtained for (M,R)-6 and (P,R)-6 were found to be [a]D 1900 (c 0.05, CHCl3) and + 1200 (c 0.05, CHCl3), respectively. The very high specific rotation values are a common feature of helical structures, while the sign of the optical rotation allows reliable assignment of the helical configuration.21,22 Treatment of the resulting optically active diastereomers (M,R)6 and (P,R)-6 with a solution of potassium hydroxide in refluxing ethanol gave the corresponding alcohols (M)-( )-4 and (P)-(+)-4, respectively, in good yields (Scheme 2).23 In summary, we have developed a synthetic approach and have undertaken enantiomeric resolution of the new hydroxyhexahelicene 4. We completed the synthesis of racemic 4 in only four steps with an overall 55% yield. We also demonstrated that (R)-2-phthalimidopropanoic acid chloride 5 was a suitable resolving agent for the helically-chiral alcohol. This helicene could serve as a ligand in asymmetric synthesis or as a building block for supramolecular architectures. Work in this field is currently in progress. Acknowledgments The authors are grateful to Pascal Retailleau for the X-ray analysis and to the DGRS (Direction Générale de la Recherche Scientifique) of the Tunisian Ministry of Higher Education and Scientific Research for financial support.
S. Moussa et al. / Tetrahedron Letters 53 (2012) 5824–5827
Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.tetlet.2012.07. 076. References and notes 1. (a) Urbano, A. Angew. Chem., Int. Ed. 2003, 42, 3986–3989; (b) Katz, T. J. Angew. Chem,. Int. Ed. 2000, 39, 1921–1923; (c) Meurer, K. P.; Vögtle, F. Top. Curr. Chem. 1985, 127, 1–76; (d) Laarhoven, W. H.; Prinsen, W. J. C. Top. Curr. Chem. 1984, 125, 63–130. 2. (a) Xu, Y.; Zhang, Y. X.; Sugiyama, H.; Umano, T.; Osuga, H.; Tanaka, K. J. Am. Chem. Soc. 2004, 126, 6566–6567; (b) Fasel, R.; Parschau, M.; Ernst, K. H. Angew. Chem., Int. Ed. 2003, 42, 5178–5181; (c) Reetz, M. T.; Sostmann, S. Tetrahedron 2001, 57, 2515–2520; (d) Reetz, M. T.; Sostmann, S. J. Organomet. Chem. 2000, 603, 105–109; (e) Weix, D. J.; Dreher, S. D.; Katz, T. J. J. Am. Chem. Soc. 2000, 122, 10027–10032; (f) Verbiest, T.; Van Elshocht, S.; Kauranen, M.; Hellemans, L.; Snauwaert, J.; Nuckolls, C.; Katz, T. J.; Persoons, A. Science 1998, 282, 913–915; (g) Kelly, T. R.; Sestelo, J. P.; Tellitu, I. J. Org. Chem. 1998, 63, 3655–3665; (h) Owens, L.; Thilgen, C.; Diederich, F.; Knobler, C. B. Helv. Chim. Acta 1993, 76, 2757–2774; (i) Ben.Hassine, B.; Gorsane, M.; Pecher, J.; Martin, R. H. Bull. Soc. Chim. Belg. 1986, 95, 547–556. 3. (a) Treboux, G.; Lapstun, P.; Wu, Z. H.; Silverbrook, K. Chem. Phys. Lett. 1999, 301, 493–497; (b) Jalaie, M.; Weatherhead, S.; Lipkowitz, K. B.; Robertson, D. Electron. J. Theor. Chem. 1997, 2, 268–272. 4. (a) Newman, M. S.; Lutz, W. B.; Lednitzer, D. J. Am. Chem. Soc. 1955, 77, 3420– 3421; (b) Newman, M. S.; Lednicer, D. J. Am. Chem. Soc. 1956, 78, 4765–4770. 5. Beljonne, D.; Shuai, Z.; Bredas, J. L.; Kauranen, M.; Verbiest, T.; Persoons, A. J. Chem. Phys. 1998, 108, 1301–1304. 6. Caronna, T.; Sinisi, R.; Catellani, M.; Luzzati, S.; Abbate, S.; Longhi, G. Synth. Met. 2001, 119, 79–80. 7. Sahasithiwat, S.; Mophuang, T.; Menbangpung, L.; Kamtonwong, S.; Sooksimuang, T. Synth. Met. 2010, 160, 1148–1152. 8. Wynberg, H. Acc. Chem. Res. 1971, 4, 65–67. 9. Maiorana, S.; Papagni, A.; Licandro, E.; Annunziata, R.; Parravidino, P.; Perdicchia, D.; Giannini, C.; Bencini, M.; Clays, K.; Persoons, A. Tetrahedron 2003, 59, 6481–6488. 10. Collins, S. K.; Vachon, M. P. Org. Biomol. Chem. 2006, 4, 2518–2524. 11. Tovar, J. D.; Rose, A.; Swager, T. M. J. Am. Chem. Soc. 2002, 124, 7762–7769. 12. Aloui, F.; Moussa, S.; Ben Hassine, B. Tetrahedron Lett. 2011, 52, 572–575. 13. Spectroscopic data for diarylethene 2: colorless solid, showing a violet fluorescence when dissolved in CH2Cl2, Rf = 0.5 (cyclohexane/EtOAc, 98:2); mp = 171–173 °C; 1H NMR (300 MHz, CDCl3): d (ppm): 3.87 (s, 3H, OCH3), 6.96 (d, J = 8.7 Hz, 2H), 7.24–7.31 (m, 2H), 7.50–7.67 (m, 3H), 7.82–7.91 (m, 3 H), 7.94–8.02 (m, 2H), 8.91 (d, J = 8.1 Hz, 2H), 8.95 (s, 1H); 13C NMR (75 MHz, CDCl3): d (ppm): 55.41 (OCH3), 114.26 (2 CH), 120.84 (CH), 122.11 (CH), 122.17 (C), 123.29 (CH), 124.79 (CH), 124.90 (CH), 125.30 (C), 127.12 (CH), 127.61 (CH), 127.98 (2 CH), 128.20 (C), 129.30 (C), 129.79 (CH), 130.13 (CH), 131.07 (C), 139.29 (CH), 123.24 (CH), 136.49 (C), 139,09 (C), 139.61 (C), 159.54 (C–O); ESI-MS: m/z = 366.10 [M]+. 14. Liu, L.; Yang, B.; Katz, T. J.; Poindexter, M. K. J. Org. Chem. 1991, 56, 3769–3775. 15. Spectroscopic data for 14-methoxy-5-thiahexahelicene 3: pale yellow solid; Rf = 0.52 (cyclohexane/EtOAc, 98:2); mp = 218–220 °C; 1H NMR (300 MHz, CDCl3): d (ppm): 2.80 (s, 3H, OCH3), 6.80 (ddd, J1 = 1.2 Hz, J2 = 6.9 Hz, J3 = 8.1 Hz, 1H), 6.87 (d, J = 7.8 Hz, 1H), 7.01 (dd, J1 = 2.4 Hz, J2 = 8.7 Hz, 1H), 7.16–7.24 (m, 2H), 7.78 (d, J = 8.4 Hz, 1H), 7.82–7.86 (m, 3H), 7.91 (d, J = 8.7 Hz, 1H), 7.93 (d, J = 8.1 Hz, 1H), 7.96 (d, J = 8.4 Hz, 1H), 8.02 (d, J = 8.4 Hz, 1H); 13C NMR (75 MHz, CDCl3): d (ppm): 54.63 (OCH3), 109.47 (CH), 118.14 (CH), 121.59 (CH), 122.42 (CH), 123.00 (CH), 124.20 (CH), 125.21 (C), 125.33 (C), 125.87 (CH), 126.65 (CH), 127.01 (C), 127.08 (CH), 127.54 (CH), 127.88 (CH), 128.23 (CH), 129.72 (CH), 131.30 (C), 131.46 (C), 131.84 (C), 133.22 (C), 136.59 (C), 138.51 (C), 139.76 (C), 157.73 (C); HRMS (MALDI-TOF) calcd for C25H16OS
16. 17. 18.
19.
20.
21. 22.
23.
5827
[M]+: 364.09218. Found: 364.09162. Crystal data for compound 3 (C25H16OS) were recorded on a Bruker SMART CCD diffractometer, M = 365.44, monoclinic, space group P21. a = 10.0862(7) Å, b = 6.5339(4) Å, c = 13.6536(10) Å, V = 899.80(11) Å3, Z = 2, qcalcd = 1.345 g/cm3, X-ray source CuKa, k = 1.54187 Å, T = 293(2) K, measured reflections 2974, independent reflections 1707, reflections used 1707, refinement type Fsqd, parameters refined 238, R1 = 0.1536, wR2 = 0.3652. Crystallographic data for the structure have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 851811. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44(0)-1223-336033 or email: [email protected]. Navaza, J.; Tsoucaris, G.; le Bas, G.; Navaza, A.; de Rango, C. Bull. Soc. Chim. Belg. 1979, 88, 863–870. Ogawa, Y.; Toyama, M.; Karikomi, M.; Seki, K.; Hagaa, K.; Uyehara, T. Tetrahedron Lett. 2003, 44, 2167–2170. Bossi, A.; Licandro, E.; Maiorana, S.; Rigamonti, C.; Righetto, S.; Stephenson, G. R.; Spassova, M.; Botek, E.; Champagne, B. J.Phys. Chem. C 2008, 112, 7900– 7907. Spectroscopic data for diastereomer (M,R)-6: yellow solid, 79% de; mp = 156– 158 °C; Rf = 0.32 (cyclohexane/EtOAc, 90:10); [a]D 1900 (c 0.05, CHCl3); 1H NMR (300 MHz, CDCl3): d (ppm): 1.58 (d, J = 4.2 Hz, 3H, CH3), 4.95 (q, J = 5.7 Hz, 1H, CHN), 6.83 (ddd, J1 = 1.2 Hz, J2 = 6.9 Hz, J3 = 8.1 Hz, 1H), 6.86 (d, J = 8.1 Hz, 1H), 7.11 (ddd, J1 = 1.5 Hz, J2 = 6.9 Hz, J3 = 8.1 Hz, 1H), 7.30 (dd, J1 = 2.4 Hz, J 2 = 8.7 Hz, 1H), 7.54 (d, J = 2.1 Hz, 1H), 7.79–7.82 (m, 3H), 7.88–7.94 (m, 3H), 7.97–8.03 (m, 5H), 8.12 (d, J = 8.7 Hz, 1H); 13C NMR (75 MHz, CDCl3): d (ppm): 15.61 (CH3), 47.50 (CHN), 120.62 (CH), 121.02 (CH), 122.23 (CH), 122.50 (C), 123.12 (CH), 123.93 (C), 124.03 (2 CH), 124.99 (C), 125.53 (C), 125.60 (CH), 126.23 (CH), 126.41 (CH), 126.66 (CH), 127.35 (CH), 128.03 (CH), 128.42 (CH), 129.44 (CH), 130.02 (C), 131.16 (C), 131.29 (C), 131.93 (C), 132.19 (CH), 132.89 (C), 134.55 (2 CH), 136.06 (C), 138.42 (C), 140.12 (C), 148.69 (C), 167.37 (2 C–O), 168.43 (CO). Spectroscopic data for diastereomer (P,R)-6: yellow solid, 70% de; mp = 202– 204 °C; Rf = 0.34 (cyclohexane/EtOAc, 90:10); [a]D +1200 (c 0.05, CHCl3); 1H NMR (300 MHz, CDCl3): d (ppm): 1.58 (d, J = 4.2 Hz, 3H, CH3), 4.91 (q, J = 7.2 Hz, 1H, CHN), 6.71 (ddd, J1 = 0.9 Hz, J2 = 6.9 Hz, J3 = 8.1 Hz, 1H), 6.83 (d, J = 8.1 Hz, 1H), 6.95 (ddd, J1 = 1.2 Hz, J1 = 6.9 Hz, J3 = 8.1 Hz, 1H), 7.29 (dd, J1 = 2.1 Hz, J2 = 8.7 Hz, 1H), 7.55 (d, J = 2.1 Hz, 1H), 7.74–7.80 (m, 3H), 7.85–7.93 (m, 3H), 7.96–8.03 (m, 5H), 8.07 (d, J = 8.4 Hz, 1H); 13C NMR (75 MHz, CDCl3): d (ppm): 15.29 (CH3), 47.32 (CHN), 120.10 (CH), 120.31 (CH), 121.75 (CH), 122.15 (CH), 122.63 (CH), 123.58 (2 CH), 124.51 (C), 125.17 (CH), 125.88 (CH), 126.00 (CH), 126.29 (CH), 126.96 (CH), 127.68 (CH), 128.04 (CH), 129.05 (CH), 129.62 (C), 130.49 (C), 130.74 (C), 131.57 (C), 131.97 (C), 132.54 (C), 134.21 (2 CH), 134.62 (C), 135.74 (C), 136.09 (C), 138.36 (C), 139.90 (C), 148.39 (C), 167.12 (2 CO), 168.01 (CO). For an early review, see: Martin, R. H. Angew. Chem., Int. Ed. Engl. 1974, 13, 649– 660. In carbohelicenes known so far, ( )-enantiomers always have the (M) helicity Grimme, S.; Harren, J.; Sobanski, A.; Vögtle, F. Eur. J. Org. Chem. 1998, 1491– 1509. Selected spectral data for (M)-( )-14-hydroxy-5-thiahexahelicene (4): pale yellow solid; mp = 283–285 °C; Rf = 0.23 (cyclohexane/EtOAc 95:5); [a]D 1787 (c 0.08, CHCl3); 1H NMR (300 MHz, CDCl3): d (ppm): 4.51 (s, 1H, OH), 6.80 (ddd, J1 = 1.2 Hz, J2 = 6.9 Hz, J3 = 8.1 Hz, 1H), 6.89 (d, J = 7.8 Hz, 1H), 6.97 (dd, J1 = 2.4 Hz, J2 = 8.7 Hz, 1H), 7.14–7.24 (m, 2H), 7.73 (d, J = 8.4 Hz, 1H), 7.78 (d, J = 8.4 Hz, 1H), 7.81 (d, J = 8.4 Hz, 1H), 7.82–7.86 (m, 2H), 7.90 (d, J = 8.4 Hz, 1H), 7.92 (d, J = 8.4 Hz, 1H), 8.00 (d, J = 8.4 Hz, 1H); 13C NMR (75 MHz, CDCl3): d (ppm): 112.45 (CH), 116.42 (CH), 121.28 (CH), 122.00 (CH), 122.71 (CH), 123.71 (CH), 124.62 (C), 124.84 (C), 125.59 (CH), 126.14 (CH), 126.50 (C), 126.58 (CH), 127.10 (CH), 127.61 (CH), 127.95 (CH), 129.76 (CH), 131.10 (C), 131.36 (C), 131.53 (C), 132.96 (C), 136.04 (C), 138.16 (C), 139.37 (C), 153.87 (C– O); HRMS (MALDI-TOF) calcd for C24H15OS [M+H]+: 351.08436. Found: 351.08312. (P)-(+)-14-hydroxy-5-thiahexahelicene (4): pale yellow solid; mp = 284–286 °C; Rf = 0.23 (cyclohexane/EtOAc 95:5); [a]D +1187 (c 0.07, CHCl3); ESI-MS: m/z = 351 [M+H]+.