Functionalized Heptahelicene Bidentate Ligands and Chiral Building Blocks

Abstract

Syntheses of functionalized heptahelicenes 11-13 disubstituted at positions 3 and 16 by hydroxymethyl or bromomethyl functions are described as a new series of bidentate ligands or chiral building blocks. Those functions are flexible enough and properly positioned for a possible chelate effect onto a metal center. Photocyclodehydrogenation, phase-transfer-catalyzed Wittig reaction, and use of THP groups for increasing solubility and further functional group transformations were key elements in this synthetic route.

arenes - chirality - helical structures - chelates - supramolecular chemistry

References

1

Former address: Organic Chemistry Division, Laboratory of Supramolecular Chemistry and Catalysis, Faculty of Sciences, Université Libre de Bruxelles, C.P. 160-06, 50 Ave. F. D. Roosevelt, 1050 Brussels, Belgium.

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6a Bender TP. Qi Y. Desjardins P. Wang ZY. Can. J. Chem.  1999,  77:  1444 

Liquid crystals:

6b Nuckolls C. Katz TJ. J. Am. Chem. Soc.  1998,  120:  9541 

Fibers:

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6d Nuckolls C. Katz TJ. Castellanos L. J. Am. Chem. Soc.  1996,  118:  377 

Polymers, films, monolayers:

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Molecular electronics, optics and switches:

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6r Beljonne D. Kauranen M. Zhuai Z. Verbiest T. Persoons A. Bredas JL. Polym. Prepr., Am. Chem. Soc. Div. Polym. Chem.  1998,  39:  1117 

6s Chen C.-T. Chou Y.-C. J. Am. Chem. Soc.  2000,  122:  7662 

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7c Murguly E. McDonald R. Branda NR. Org. Lett.  2000,  2:  3169 

Heptahelicenes, excluding heterohelicenes:

8a Carreño MC. González-López M. Urbano A. Chem. Commun.  2005,  5:  611 

8b El Abed R. Ben Hassine B. Genêt J.-P. Gorsane M. Marinetti A. Eur. J. Org. Chem.  2004,  1517 

8c Wang DZ. Katz TJ. Golen J. Rheingold AL. J. Org. Chem.  2004,  69:  7769 

8d Peña D. Cobas A. Pérez D. Guitián E. Castedo L. Org. Lett.  2003,  5:  1863 

8e Paruch K. Vyklicky L. Wang DZ. Katz TJ. Incarvito C. Zakharov L. Rheingold AL. J. Org. Chem.  2003,  68:  8539 

8f Tepl F. Stará IG. Star I. Kollároviè A. aman D. Rulièek L. Fiedler P. J. Am. Chem. Soc.  2002,  124:  9175 

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8q Bernstein WJ. Calvin M. Buchardt O. J. Am. Chem. Soc.  1973,  95:  527 

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Stoichiometric asymmetric reactions:

9a Ben Hassine B. Gorsane M. Pecher J. Martin RH. Bull. Soc. Chim. Belg.  1987,  96:  801 

9b Hassine B. Gorsane M. Geerts-Evrard F. Pecher J. Martin RH. Castelet D. Bull. Soc. Chim. Belg.  1986,  95:  547 

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9d Ben Hassine B. Gorsane M. Pecher J. Martin RH. Bull. Soc. Chim. Belg.  1985,  94:  597 

10 Meurer KP. Vögtle F. Top. Curr. Chem.  1985,  127:  32 ; and references therein

Racemization of heptahelicene was evaluated: ΔΔG¹ = 41.7 kcal/mol.

11a Martin RH. Marchant M.-J. Tetrahedron  1974,  30:  347 

11b Janke RH. Haufe G. Wurthwein E.-U. Borkent JH. J. Am. Chem. Soc.  1996,  118:  6031 

12 Vanderwerf WD. inventors; US Pat.  3,288,823. Among several preparations: ; Chem. Abstr. , 37699

For similar derivatives:

13a Ackerley N. Brewster AG. Brown GR. Clarke DS. Foubister AJ. Griffin SJ. Hudson JA. Smithers MJ. Whittamore PRO. J. Med. Chem.  1995,  38:  1608 

13b

6-Tetrahydropyranyloxy-methyl-2-naphthalene Carboxaldehyde (8).
Alcohol 7 (2.221 g, 8.16 mmol) was dissolved in distilled benzene (35 mL) at 20 °C and MnO₂ (3.60 g, 50.7 mmol) was added to the solution. The resulting black suspension was refluxed for 3 h. After filtration on a short column of silica gel and evaporation of solvent, compound 8 was recovered as a solid (1.789 g, 6.62 mmol, 81% yield). ¹H NMR (250 MHz, CDCl₃): δ = 1.50-2.00 (6 H, m, CH₂), 3.50-3.65 (1 H, m, CH₂O), 3.90-4.05 (1 H, m, CH₂O), 4.70 (1 H, d, J = 12.8 Hz, naphthyl-CH₂O), 4.77 (1 H, app t, J = 3.3 Hz, O-CH-O), 4.98 (1 H, d, J = 12.8 Hz, naphthyl-CH₂O), 7.58 (1 H, dd, J = 1.5 Hz, 8.4 Hz, H arom.), 7.85-8.00 (4 H, m, H arom.), 8.31 (1 H, s, H arom.), 10.14 (1 H, s, CHO). ¹³C NMR (62.9 MHz, CDCl₃): δ = 19.4 (CH₂), 25.5 (CH₂), 30.6 (CH₂), 62.2 (CH₂-O), 68.6 (CH₂-O), 98.1 (O-CH-O), 123.1 (CH arom.), 126.2 (CH arom.), 126.9 (CH arom.), 129.0 (CH arom.), 129.6 (CH arom.), 130.7 (C arom.), 132.1 (C arom.), 134.1 (CH arom.), 136.5 (C arom.), 139.7 (C arom.), 192.0 (CHO). MS (EI, 70 eV): m/z (%) = 270 (4.6) [M⁺], 186 (8.5) [M⁺ - C₅H₈O], 169 (100) [M⁺ - OTHP], 141 (35) [M⁺ - CHO - OTHP]. R _f = 0.63 (TLC, SiO₂, CH₂Cl₂-EtOAc, 95:5).

14

Synthesis of Bis(stilbene) 9. At 20 °C, aldehyde 8 (2.658 g, 9.84 mmol) was dissolved in CH₂Cl₂ (50 mL), followed by addition of phosphonium salt 3 (4.266 g, 4.92 mmol) and an aq solution of 5 M KOH (50 mL). After vigorous stirring for 15 h, the organic layer was separated and dried over anhyd MgSO₄. After filtration and evaporation of the solvent, the expected bis(stilbene) was purified on a SiO₂ flash chromatography column using CH₂Cl₂-MeOH (98:2) as eluent. Bis(stilbene) (9) was obtained as a solid (isomeric mixture, 2.85g. 4.13 mmol, 84% yield). ¹H NMR (250 MHz, CDCl₂CDCl₂, isomeric mixture): δ = 1.40-2.00 (m, 12 H, CH₂), 3.40-3.60 (m, 2 H, CH₂-O), 3.85-4.00 (m, 2 H, CH₂-O), 4.50-4.75 (m, 4 H, naphthyl-CH₂, O-CH-O), 4.85-5.00 (m, 2 H,), 6.90-7.30 (m, 2 H, CH=CH), 7.40-8.00 (m, 16 H, H arom.), 8.26 (s, 1 H, H arom. CH=CBr). ¹³C NMR (62.9 MHz, CDCl₂CDCl₂, isomeric mixture): δ = 19.4 (CH₂), 25.4 (CH₂), 30.6 (CH₂), 62.2 (CH₂-O), 68.7 (CH₂-O), 97.9 (O-CH-O), 123.0 (CH arom.), 123.70-139.83 (multiple signals from an isomeric mixture). MS (EI, 70 eV): m/z (%) = 690 (3.4) [M⁺ (⁸¹Br)], 688 (3.2) [M⁺ (⁷⁹Br)], 606 (13) [M⁺ (⁸¹Br) - C₅H₈O], 604 (14) [M⁺ (⁷⁹Br) - C₅H₈O], 522 (88) [M⁺ (⁸¹Br) - C₁₀H₁₆O₂], 520 (100) [M⁺ (⁷⁹Br) - C₁₀H₁₆O₂]. HRMS (EI, 70 eV): m/z (%) = 690.2193 [M⁺ (⁸¹Br), exp.; 690.2168 calcd], 688.2192 [M⁺ (⁷⁹Br), exp.; 688.2188 calcd], 522.1004 [M⁺ (⁸¹Br) - C₁₀H₁₆O₂, exp.; 522.1017 calcd], 520.0999 [M⁺ (⁷⁹Br) - C₁₀H₁₆O₂, exp.; 520.1038 calcd].

15a

Ref. 8m.

15b Liu L. Katz TJ. Tetrahedron Lett.  1991,  32:  6831 

16

Photocyclodehydrogenation Procedure to 10.
In a photochemical reactor equipped with a water cooling jacket and a stir bar, compound 9 (0.420 g, 0.609 mmol), iodine (309 mg, 1.22 mmol) and 1,2-epoxybutane (8.0 mL) were dissolved in high purity grade benzene (700 mL). Nitrogen gas was bubbled through the solution within 30 min while stirring vigorously for removing oxygen prior to irradiation with a high-pressure mercury lamp for 3 h. When the reaction was complete, excess of iodine was reduced with a 15% aqueous solution of Na₂S₂O₃ (20 mL). The aqueous phase was separated and the organic layer dried over MgSO₄. After filtration and evaporation of solvent, the crude was purified by flash chromatography on silica gel with CH₂Cl₂-EtOAc (98:2) and then (95:5). Helicene 10 was obtained as a yellow solid (0.270 g, 0.393 mmol, 65% yield). ¹H NMR (250 MHz, CDCl₂CDCl₂): δ = 1.40-2.00 (m, 12 H, CH₂), 3.50 (m, 2 H, CH₂-O), 3.85 (m, 2 H, CH₂-O), 4.36 (d, J = 12.4 Hz, 2 H, naphthyl-CH₂), 4.52 (m, 4 H, O-CH-O, naphthyl-CH₂), 6.39 (d, J = 7.0 Hz, 1 H, H arom.), 6.42 (d, J = 7.7 Hz, 1 H, H arom.), 6.98 (d, J = 7.3 Hz, 2 H, H arom.), 7.22 (s, 1 H, H arom.), 7.24 (s, 1 H, H arom), 7.70 (d, J = 8.8 Hz, 1 H, H arom.), 7.74 (d, J = 8.8 Hz, 1 H, H arom.), 7.40-7.50 (m, 2 H, H arom.), 7.87 (d, J = 8.0 Hz, 1 H, H arom.), 7.92 (d, J = 8.0 Hz, 1 H, H arom.), 7.99 (d, J = 8.8 Hz, 1 H, H arom.), 8.32 (s, 1 H, H arom. CH=CBr), 8.42 (d, J = 8.4 Hz, 1 H, H arom.). ¹³C NMR (62.9 MHz, CDCl₂CDCl₂, DEPT): δ = 19.3 (CH₂), 25.5 (CH₂), 30.6 (CH₂), 62.0 (CH₂O), 67.7 (CH₂O), 96.9 (OCHO), 121.1 (C arom.), 123.7 (CH arom.), 123.9 (CH arom.), 124.0 (CH arom.), 124.3 (CH arom.), 124.6 (C arom.), 125.2 (CH arom.), 125.3 (CH arom.), 125.4 (CH arom.), 125.6 (CH arom.), 125.9 (CH arom.), 126.9 (C arom.), 127.4 (CH arom.), 127.6 (C arom.), 127.9 (CH arom.), 128.3 (CH arom.), 128.4 (C arom.), 128.6 (C arom.), 129.9 (CH arom.), 130.2 (C arom.), 130.8 (C arom.), 131.4 (C arom.), 131.5 (C arom.), 131.9 (C arom.), 135.1 (C arom.). MS (EI, 70 eV): m/z (%) = 686 (45) [M⁺ (⁸¹Br)], 684 (43) [M⁺ (⁷⁹Br)], 602 (41) [M⁺ (⁸¹Br) - C₅H₈O], 600(39) [M⁺ (⁷⁹Br) - C₅H₈O], 520 (25) [M⁺ (⁸¹Br) - 2OTHP], 518 (30) [M⁺ (⁷⁹Br) - 2OTHP]. R _f = 0.42 (TLC, SiO₂, CH₂Cl₂-EtOAc, 98:2).

17

9-Bromo-3,16-bis(hydroxymethyl)heptahelicene (11).
Compound 10 (83.2 mg, 0.121 mmol) was added to EtOH (25 mL) as a suspension at 20 °C, followed by p-toluene-sulfonic acid hydrate as catalyst (5.0 mg, 0.0026 mmol). After vigorous stirring for 15 h, the solvent was evaporated and crude diol 11 was purified by flash chromatography on SiO₂ with CH₂Cl₂-EtOAc (80:20) and then pure EtOAc as eluent. Pure diol 11 was obtained (50.1 mg, 0.097 mmol, 80% yield). ¹H NMR (250 MHz, DMSO-d ₆): δ = 4.35 (4 H, CH₂OH), 5.10 (2 H, large, OH), 6.36 (dd, J = 1.1 Hz, J = 8.8 Hz, 2 H, CH), 6.86 (dd, J = 2.2 Hz, J = 8.8 Hz, 2 H, CH), 7.34 (2 H, app. s, CH arom.), 7.61 (1 H, d, J = 8.0 Hz, CH), 7.64 (d, 1 H, J = 8.0 Hz, CH), 7.84 (d, 1 H, J = 8.9 Hz, CH), 7.88 (d, 1 H, J = 9.1 Hz, CH), 8.10 (s, 2 H, CH arom.), 8.18 (d, 1 H, J = 8.4 Hz, CH), 8.35 (d, 1 H, J = 8.4 Hz, CH), 8.57 (s, 1 H, CH arom.). ¹³C NMR (62.9 MHz, DMSO-d ₆, DEPT): δ = 62.4 (CH₂OH), 120.3 (C), 122.6 (CH), 123.1 (CH), 123.5 (CH), 124.1 (C), 124.6 (CH), 125.4 (CH arom.), 125.6 (CH), 125.7 (CH), 126.5 (C), 127.5 (C), 127.7 (C), 127.9 (CH), 128.4 (CH), 128.7 (CH), 128.8 (CH), 129.4 (C), 129.9 (CH), 130.5 (C), 130.6 (C), 131.6 (C), 131.7 (C), 139.5 (C), 139.6 (C). MS (EI, 70 eV): m/z (%) = 518 (66) [M⁺ (⁸¹Br)], 516 (100) [M⁺ (⁷⁹Br)], 374 (60) [M⁺ - HBr - CH₂OH -CH₂OH], 187 (51) [C₃₀H₁₄ ⁺⁺]. R _f = 0.05 (TLC, SiO₂, CH₂Cl₂-EtOAc, 4:1).