Synthesis of a Novel Unsymmetrical
Bisoxazoline Ligand with sp² Bridging Carbon

Ruslan Yuryev; Andreas Liese

doi:10.1055/s-0029-1217760

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Synlett 2009(16): 2589-2592
DOI: 10.1055/s-0029-1217760

LETTER

Synthesis of a Novel Unsymmetrical Bisoxazoline Ligand with sp^² 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
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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.

Key words

bisoxazoline ligands - asymmetric catalysis - asymmetric synthesis - transition-metal complexes - Henry reaction

References and Notes

1 Yoon TP. Jacobsen EN. Science 2003, 299: 1691

Crossref PubMed Search in Google Scholar
For a review, see:
2a Desimoni G. Faita G. Jørgensen KA. Chem. Rev. 2006, 106: 3561

Search in Google Scholar
2b Ghosh AK. Bilcer G. Fidanze S. In The Chemistry of Heterocyclic Compounds Vol. 60: Palmer DC. John Wiley and Sons; New York: 2004. p.529

Search in Google Scholar
2c Johnson JS. Evans DA. Acc. Chem. Res. 2000, 33: 325

Search in Google Scholar
2d Ghosh AK. Mathivanan P. Cappiello J. Tetrahedron: Asymmetry 1998, 9: 1

Search in Google Scholar
3 For a review, see: Rechavi D. Lemaire M. Chem. Rev. 2002, 102: 3467

Crossref Search in Google Scholar
4a Lee SS. Hadinoto S. Yinga JY. Adv. Synth. Catal. 2006, 348: 1248

Search in Google Scholar
4b Benaglia M. Cinquini M. Cozzi F. Celentano G. Org. Biomol. Chem. 2004, 2: 3401

Search in Google Scholar
4c Corma A. Garcia H. Moussaif A. Sabater MJ. Zniber R. Redouane A. Chem. Commun. 2002, 1058
4d Annunziata R. Benaglia M. Cinquini M. Cozzi F. Pitillo M. J. Org. Chem. 2001, 66: 3160

Search in Google Scholar
4e Orlandi S. Mandoli A. Pini D. Salvadori P. Angew. Chem. Int. Ed. 2001, 40: 2519

Search in Google Scholar
5 Chollet G. Rodriguez F. Schulz E. Org. Lett. 2006, 8: 539

Crossref Search in Google Scholar
6 Sibi MP. Chen J. Org. Lett. 2002, 4: 2933

Crossref PubMed Search in Google Scholar
9a Lange’s Handbook of Chemistry Dean JA. McGraw-Hill; New York: 1999.
9b Hammett LP. J. Am. Chem. Soc. 1937, 59: 96

Search in Google Scholar
10 Heitler C. J. Chem. Soc. 1963, 4885

Crossref
11 Porter GR. Rydon HN. Schofield JA. Nature (London) 1958, 182: 927

Crossref Search in Google Scholar
12 Park JK. Kim S.-W. Hyeon T. Kim BM. Tetrahedron: Asymmetry 2001, 12: 2931

Crossref Search in Google Scholar
For selected examples on the recovery of organometallic catalysts by solvent resistant nanofiltration, see:
13a Beigi M. Haag R. Liese A. Adv. Synth. Catal. 2008, 350: 919

Search in Google Scholar
13b Greiner L. Laue S. Wöltinger J. Liese A. Top. Curr. Chem. 2007, 276: 111

Search in Google Scholar
13c Scarpello JT. Nair D. Freitas dos Santos LM. White LS. Livingston AG. J. Membr. Sci. 2002, 203: 71

Search in Google Scholar
13d Wöltinger J. Drauz K. Bommarius AS. Appl. Catal., A 2001, 221: 171

Search in Google Scholar
13e Wöltinger J. Bommarius AS. Drauz K. Wandrey C. Org. Process Res. Dev. 2001, 5: 241

Search in Google Scholar
15a Ginotra SK. Singh VK. Org. Biomol. Chem. 2007, 5: 3932

Search in Google Scholar
15b Evans DA. Seidel D. Rueping M. Lam HW. Shaw JT. Downey CW. J. Am. Chem. Soc. 2003, 125: 12692

Search in Google Scholar
15c Christensen C. Juhl K. Hazell RG. Jørgensen KA. J. Org. Chem. 2002, 67: 4875

Search in Google Scholar
15d Christensen C. Juhl K. Jørgensen KA. Chem. Commun. 2001, 2222
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.
For discussion on the influence of ligand bite angle on the enantioselectivity in the Diels-Alder reaction, see:
17a Lipkowitz KB. Pradhan M. J. Org. Chem. 2003, 68: 4648

Search in Google Scholar
17b Lipkowitz KB. Schefzick S. J. Am. Chem. Soc. 2001, 123: 6710

Search in Google Scholar
17c van Leeuwen PWNM. Kamer PCJ. Reek JNH. Dierkes P. Chem. Rev. 2000, 100: 2741

Search in Google Scholar
17d Davies IW. Gerena L. Cai D. Larsen RD. Verhoeven TR. Reider PJ. Tetrahedron Lett. 1997, 38: 1145

Search in Google Scholar
17e Davies IW. Gerena L. Castonguay L. Senanayake CH. Larsen RD. Verhoeven TR. Reider PJ. Chem. Commun. 1996, 1753

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.