Synlett 2009(16): 2589-2592  
DOI: 10.1055/s-0029-1217760
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of a Novel Unsymmetrical Bisoxazoline Ligand with sp² Bridging Carbon

Ruslan Yuryev, Andreas Liese*
Institute of Technical Biocatalysis, Hamburg University of Technology, Denickestr. 15, Hamburg 21073, Germany
Fax: +49(40)428782127; e-Mail: liese@tuhh.de;
Further Information

Publication History

Received 30 April 2009
Publication Date:
03 September 2009 (online)

Abstract

A novel unsymmetrical bisoxazoline ligand was synthesized in one step by the Knoevenagel condensation of aldehydes with a C 2-symmetric indane-derived bisoxazoline having two acidic hydrogens connected to the bridging carbon. The electronic properties of incorporated bridge substituent due to π-π conjugation with oxazoline rings can affect the catalytic performance of the ligand in asymmetric syntheses, as was shown for the Henry reaction between benzaldehyde and nitromethane.

    References and Notes

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  • HPLC conditions used
  • 16a

    for quantification of 2-nitro-1-phenylethanol and benzaldehyde: RP-8 column (Merck), 30 ˚C, 67 mM KH2PO4-MeOH (65:35), 2 mL/min, 225 nm;

  • 16b

    for determination of ee of 2-nitro-1-phenylethanol: OD-RH column (Chiralcel), 5 ˚C, MeOH-H2O (65:35), 0.2 mL/min, 225 nm.

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7

Representative Procedure for the Synthesis of Ligands 1-7
IndaBOX (1 mmol), aldehyde (1 mmol), and piperidinium acetate (0.2 mmol) were dissolved in pyridine (5 mL) at 65 ˚C while stirring. The obtained solution was maintained at the same temperature for 24 h. At the end the solvent is evaporated in vacuo and the solid residue purified by column chromatography on silica using EtOAc as an eluent. For the synthesis of ligand 7 only 0.05 mmol of aldehyde was added, and a EtOAc-MeOH mixture (10:1) was used as an eluent. Ligand 6 was isolated by pouring the reaction mixture into H2O (50 mL), filtering the precipitate, and washing it on the filter with i-PrOH (25 mL) and CH2Cl2 (25 mL).

8

Characterization Data for Ligands 1-7
2,2′-(2-Cyclohexylethene-1,1-diyl)bis(8,8a-dihydro-3a H -indeno[1,2- d ]oxazole) (1)
¹H NMR (400 MHz, CDCl3): δ = 7.47-7.37 (m, 2 H), 7.21-7.11 (m, 6 H), 6.43 (d, J = 10.0 Hz, 1 H), 5.65 (d, J = 7.6 Hz, 1 H), 5.59 (d, J = 7.9 Hz, 1 H), 5.32 (ddd, J = 7.6, 6.5, 1.2 Hz, 1 H), 5.24 (ddd, J = 7.9, 6.7, 1.6 Hz, 1 H), 3.35 (dd, J = 18.0, 6.5 Hz, 1 H), 3.32 (dd, J = 18.3, 6.7 Hz, 1 H), 3.23-3.13 (m, 2 H), 1.89-1.74 (m, 1 H), 1.47-1.24 (m, 5 H), 0.99-0.58 (m, 5 H). ¹³C NMR (100 MHz, CDCl3): δ = 161.8, 161.1, 151.9, 142.1, 141.8, 139.8, 139.5, 128.4, 128.3, 127.4, 127.3, 125.8, 125.6, 125.2, 125.1, 118.4, 83.2, 83.0, 77.1, 76.7, 39.7, 39.5, 38.6, 31.9, 31.6, 25.6, 25.3, 25.1. MS (EI): m/z = 424 [M].
2,2′-[2-(4-Methoxyphenyl)ethene-1,1-diyl]bis(8,8a-dihydro-3a H -indeno[1,2- d ]oxazole) (2)
¹H NMR (400 MHz, CDCl3): δ = 7.45-7.07 (m, 9 H), 6.83-6.67 (m, 2 H), 6.28-6.22 (m, 2 H), 5.75 (d, J = 7.7 Hz, 1 H), 5.64 (d, J = 7.8 Hz, 1 H), 5.40-5.30 (m, 2 H), 3.63 (s, 3 H), 3.39 (dd, J = 18.1, 6.7 Hz, 1 H), 3.36 (dd, J = 18.1, 6.7 Hz, 1 H), 3.25 (d, J = 17.9 Hz, 1 H), 3.16 (d, J = 18.1 Hz, 1 H). ¹³C NMR (100 MHz, CDCl3): δ = 161.2, 160.4, 159.7, 141.0, 139.9, 139.2, 138.8, 130.4, 127.6, 126.8, 126.4, 124.9, 124.8, 124.4, 114.5, 112.6, 82.5, 82.2, 76.3, 76.0, 54.3, 38.6, 38.3. MS (EI): m/z = 447 [M - H].
2,2′-[2-(4-Chlorophenyl)ethene-1,1-diyl]bis(8,8a-dihydro-3a H -indeno[1,2- d ]oxazole) (3)
¹H NMR (400 MHz, CDCl3): δ = 7.49-7.16 (m, 9 H), 6.80-6.65 (m, 4 H), 5.75 (d, J = 7.6 Hz, 1 H), 5.68 (d, J = 7.8 Hz, 1 H), 5.36 (ddd, J = 7.2, 6.4, 0.9 Hz, 1 H), 5.33 (ddd, J = 7.2, 6.4, 1.7 Hz, 1 H), 3.38 (dd, J = 17.9, 6.7 Hz, 1 H), 3.32 (dd, J = 17.0, 6.1 Hz, 1 H), 3.26 (dd, J = 17.4, 1.0 Hz, 1 H), 3.10 (d, J = 18.0 Hz, 1 H). ¹³C NMR (100 MHz, CDCl3): δ = 162.2, 160.9, 141.6, 140.7, 140.0, 139.9, 139.7, 135.2, 132.0, 130.5, 128.7, 128.5, 128.3, 127.8, 127.5, 125.9, 125.2, 125.1, 118.9, 83.7, 83.4, 77.3, 76.9, 39.5, 39.1. MS (EI): m/z = 451 [M - H].
4-{2,2-Bis(8,8a-dihydro-3a H -indeno[1,2- d ]oxazol-2-yl)vinyl}benzonitrile (4)
¹H NMR (400 MHz, CDCl3): δ = 7.50-7.16 (m, 9 H), 6.98-6.87 (m, 4 H), 5.72 (d, J = 7.6 Hz, 1 H), 5.70 (d, J = 7.9 Hz, 1 H), 5.38-5.31 (m, 2 H), 3.39 (dd, J = 18.0, 6.7 Hz, 1 H), 3.31 (dd, J = 16.6, 6.5 Hz, 1 H), 3.26 (dd, J = 17.0, 1.1 Hz, 1 H), 3.05 (d, J = 18.2 Hz, 1 H). ¹³C NMR (100 MHz, CDCl3): δ = 161.7, 160.4, 141.4, 140.4, 139.9, 139.6, 139.0, 137.9, 131.7, 129.4, 128.9, 128.6, 127.9, 127.5, 125.9, 125.3, 125.2, 121.8, 118.5, 112.2, 84.0, 83.6, 77.4, 76.9, 39.5, 39.1. MS (EI): m/z = 442 [M - H].
2,2′-[2-(4-Nitrophenyl)ethene-1,1-diyl]bis(8,8a-dihydro-3a H -indeno[1,2- d ]oxazole) (5)
¹H NMR (400 MHz, CDCl3): δ = 7.53-7.15 (m, 11 H), 6.98-6.92 (m, 2 H), 5.72 (d, J = 6.4 Hz, 1 H), 5.70 (d, J = 6.4 Hz, 1 H), 5.38-5.32 (m, 2 H), 3.39 (dd, J = 18.0, 6.7 Hz, 1 H), 3.31 (dd, J = 17.9, 6.5 Hz, 1 H), 3.27 (dd, J = 18.0, 1.0 Hz, 1 H), 3.06 (d, J = 18.2 Hz, 1 H). ¹³C NMR (100 MHz, CDCl3): δ = 161.6, 160.3, 147.4, 141.4, 140.4, 139.9, 139.8, 139.6, 138.7, 129.6, 129.0, 128.7, 127.9, 127.5, 125.9, 125.8, 125.3, 125.2, 123.2, 122.4, 84.1, 83.6, 77.5, 76.9, 39.5, 39.1. MS (EI): m/z = 462 [M - H].
4-{2,2-Bis(8,8a-dihydro-3a H -indeno[1,2- d ]oxazol-2-yl)vinyl}phenol (6)
¹H NMR (400 MHz, DMSO-d 6): δ = 10.7 (s, 1 H), 7.38-7.16 (m, 9 H), 6.82-6.75 (m, 2 H), 6.40-6.33 (m, 2 H), 5.65 (d, J = 7.7 Hz, 1 H), 5.56 (d, J = 7.9 Hz, 1 H), 5.43-5.31 (m, 2 H), 3.40 (dd, J = 18.1, 7.0 Hz, 1 H), 3.37 (dd, J = 18.0, 6.7 Hz, 1 H), 3.09 (d, J = 17.4 Hz, 1 H), 3.05 (d, J = 17.8 Hz, 1 H). ¹³C NMR (100 MHz, DMSO-d 6): δ = 161.6, 160.1, 159.8, 141.8, 140.6, 140.1, 139.8, 139.6, 131.4, 128.4, 128.2, 127.2, 127.1, 125.4, 125.3, 125.2, 125.1, 123.3, 115.2, 113.5, 82.8, 82.5, 76.3, 76.2, 39.1, 38.8. MS (EI): m/z = 433 [M - H].
1,4-Bis{2,2-bis(8,8a-dihydro-3a H -indeno[1,2- d ]oxazol-2-yl)vinyl}benzene (7)
¹H NMR (400 MHz, CDCl3): δ = 7.49-7.14 (m, 18 H), 6.35 (s, 4 H), 5.71 (d, J = 7.7 Hz, 2 H), 5.68 (d, J = 7.9 Hz, 2 H), 5.36-5.28 (m, 4 H), 3.39 (dd, J = 18.0, 6.6 Hz, 2 H), 3.32-3.22 (m, 4 H), 3.03 (d, J = 18.1 Hz, 2 H). ¹³C NMR (100 MHz, CDCl3): δ = 162.3, 160.8, 141.7, 140.7, 140.4, 139.9, 139.7, 134.4, 129.0, 128.6, 128.5, 127.7, 127.5, 125.9, 125.8, 125.2, 125.0, 119.0, 83.6, 83.4, 77.3, 76.9, 39.6, 39.1. MS-FAB: m/z = 759 [M + H].

14

The ligands (1 equiv) were mixed with Cu(OAc)2 (1.5 equiv) in CH2Cl2 at r.t. overnight. The uncomplexed salt was removed from the resulting solutions by extraction with H2O (3×). The organic phases were dried over anhyd Na2SO4, the solvent was evaporated in vacuo yielding the complexes as dark solids.