Preparation of 1,4-Dihydroquinolines Bearing a Chiral Sulfoxide Group: New Highly Enantioselective Recyclable NADH Mimics

Stéphane Gaillard; Cyril Papamicaël; Francis Marsais; Georges Dupas; Vincent Levacher

doi:10.1055/s-2005-862350

LETTER

Preparation of 1,4-Dihydroquinolines Bearing a Chiral Sulfoxide Group: New Highly Enantioselective Recyclable NADH Mimics

Stéphane Gaillard, Cyril Papamicaël, Francis Marsais, Georges Dupas, Vincent Levacher*
Laboratoire de Chimie Organique Fine et Hétérocyclique, UMR 6014, IRCOF, CNRS, Université et INSA de Rouen, B.P. 08, 76131 Mont Saint Aignan Cédex, France
Fax: +33(2)35522962; e-Mail: vincent.levacher@insa-rouen.fr;

Abstract

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Abstract

The stereoselective preparation of 1,4-dihydroquinolines possessing a chiral sulfoxide group at C-3 is reported. These novel biomimetic NADH models (R)-1a,b have been shown to be highly enantioselective in the reduction of methyl benzoylformate, producing (R)-methyl mandelate in up to 95% ee. The corresponding quinolinium salts 4a,b have been recovered in good yields. The regenerated models 1a,b could be reused without any significant erosion of the enantioselectivity.

Key words

chiral sulfoxide - NADH models - quinoline - asymmetric reduction

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References

For leading references of NADH models bearing a sulfoxide group, see:

1a Li J. Liu Y.-C. Deng J.-G. Tetrahedron: Asymmetry 1999, 10: 4343

1b Kazuyuki M. Nishimoto N. Hidenobu M. Asuka M. Satoshi O. Yasuko I. Toshimasa I. Takeshi I. Chem. Commun. 1996, 2535

1c Obika S. Nishiyama T. Tatematsu S. Miyashita K. Iwata C. Imanishi T. Tetrahedron 1997, 53: 593

1d Obika S. Nishiyama T. Tatematsu S. Miyashita K. Imanishi T. Chem. Lett. 1996, 853

1e Obika S. Nishiyama T. Tatematsu S. Nishimoto M. Miyashita K. Imanishi T. Heterocycles 1998, 261

1f Imanishi T. Obika T. Nishiyama T. Nishimoto M. Hamano Y. Miyashita K. Iwata C. Chem. Pharm. Bull. 1996, 44: 267

For early reports on annelated NADH models, see:

2a Levacher V. Dupas G. Quéguiner G. Bourguignon J. Trends Heterocycl. Chem. 1995, 4: 293

2b Dupas G. Levacher V. Quéguiner G. Bourguignon J. Heterocycles 1994, 39: 405

2c Vitry C. Vasse J.-L. Levacher V. Dupas G. Quéguiner G. Bourguignon J. Tetrahedron 2001, 57: 3087

3

Analytical data for (R)-3a: ¹H NMR (300 MHz, CDCl₃): δ = 2.30 (3 H, s), 7.21 (2 H, d, J = 8 Hz), 7.51 (3 H, m), 7.73 (1 H, m), 7.85 (1 H, d, J = 8 Hz), 8.05 (1 H, d, J = 8 Hz), 8.53 (1 H, s), 8.76 (1 H, s). ¹³C NMR (75 MHz, CDCl₃): δ = 21.8, 125.6, 127.7, 128.3, 128.8, 129.9, 130.7, 131.7, 133.2, 139.5, 141.7, 142.9, 146.2, 149.1. Anal. Calcd for C₁₆H₁₃NOS: C, 71.88; H, 4.90; N, 5.24. Found: C, 71.78; H, 4.82; N, 5.10.

4

Enantiomeric excesses were determined by HPLC analysis using a Chiracel OJ column (250 × 4.6 mm; 10 µm). Chromatographic conditions: eluent: heptane-2-propanol = 90:10; flow rate: 1 mL min^-1; pressure: 300 psi; temperature: 19 °C; UV detection: λ = 230 nm; t _R: 22 min [(S)-enantiomer] and 26 min [(R)-enantiomer].

5a Dumouchel S. Mongin F. Trécourt F. Quéguiner G. Tetrahedron Lett. 2003, 44: 2033

5b Dumouchel S. Mongin F. Trécourt F. Quéguiner G. Tetrahedron 2003, 44: 8629

6

Analytical data for (R)-4a: ¹H NMR (300 MHz, CDCl₃): δ = 2.39 (3 H, s), 4.73 (3 H, s), 7.43 (2 H, d, J = 8 Hz), 7.81 (2 H, d, J = 8 Hz), 8.12 (1 H, t, J = 9 Hz), 8.36 (1 H, t, J = 9 Hz), 8.52 (2 H, m), 9.42 (1 H, s), 9.62 (1 H, s). ¹³C NMR (75 MHz, MeOD): δ = 21.8, 47.5, 120.6, 124.3, 127.2, 131.1, 132.4, 132.8, 132.9, 139.2, 141.3, 141.7, 142.8, 144.9, 145.8, 147.8. ¹⁹F NMR (282 MHz, CDCl₃): δ = -80.5. HRMS (CI): m/z calcd for C₁₇H₁₆NOS: 282.0953. Found: 282.0957.

7 Similar side reactions have already been observed during the reduction of 3-sulfoxide pyridinium salt under these conditions. See: Imanishi T. Hamano Y. Yoshikawa HT. Iwata C. J. Chem. Soc., Chem. Commun. 1988, 473

8

Analytical data for (R)-1a: ¹H NMR (300 MHz, CDCl₃): δ = 2.76 (3 H, s), 3.45 (1 H, d, J = 19 Hz), 3.59 (3 H, s), 4.13 (1 H, d, J = 19 Hz), 7.05 (1 H, d, J = 8 Hz), 7.27 (2 H, d, J = 8 Hz), 7.47 (1 H, m), 7.65 (3 H, m), 7.87 (2 H, d, J = 8Hz). ¹³C NMR (75 MHz, CDCl₃): δ = 21.7, 23.2, 38.9, 109.7, 112.9, 121.7, 123.3, 125.3, 127.7, 130.0, 130.2, 139.2, 139.3, 140.7, 140.8. HRMS (CI): m/z calcd for C₁₇H₁₇NOS: 283.1031. Found: 283.1035.

9 Charpentier P. Lobrégat V. Levacher V. Dupas G. Quéguiner G. Bourguignon J. Tetrahedron Lett. 1998, 39: 4013

10

Analytical data for 2b: ¹H NMR (300 MHz, CDCl₃): δ = 3.98 (3 H, s), 4.00 (3 H, s), 6.92 (1 H, s), 7.34 (1 H, s), 8.10 (1 H, s), 8.68 (1 H, s). ¹³C NMR (75 MHz, CDCl₃): δ = 56.5, 56.6, 104.5, 108.3, 115.6, 125.3, 135.8, 143.9, 149.2, 150.9, 153.0. Anal. Calcd for C₁₁H₁₀BrNO₂: C, 49.28; H, 3.76; N, 5.22. Found: C, 49.35; H, 3.82; N, 5.21.

11 Smith AB. Levenberg PA. Jerris PJ. Scarborough RM. Wovkulich PM. J. Am. Chem. Soc. 1981, 103: 1501

12 Trofimenko S. J. Org. Chem. 1963, 28: 3243

13 Analytical data for (R)-7b: ¹H NMR (300 MHz, CDCl₃): δ = 2.29 (3 H, s), 3.93 (6 H, s), 7.02 (1 H, s), 7.20 (2 H, d, J = 8 Hz), 7.33 (1 H, s), 7.51 (2 H, d, J = 8 Hz), 8.29 (1 H, s), 8.62 (1 H, s). ¹³C NMR (75 MHz, CDCl₃): δ = 21.8, 56.6, 56.7, 105.8, 108.3, 123.6, 125.4, 130.6, 131.4, 137.5, 142.1, 142.5, 144.2, 146.7, 151.1, 154.3. HRMS: m/z calcd for C₁₈H₁₇NO₃S: 327.0929. Found: 327.0933.

14

Enantiomeric excesses were determined by HPLC analysis using a Chiralpak AD column (250 × 4.6 mm; 10 µm). Chromatographic conditions: eluent: heptane-2-propanol = 85:15; flow rate: 1 mL min^-1; pressure: 300 psi; temperature: 19 °C; UV detection: λ = 230 nm; t _R = 36 min [(S)-enantiomer] and 40 min [(R)-enantiomer].

15

Analytical data for (R)-8b: ¹H NMR (300 MHz, MeOD): δ = 2.39 (3 H, s), 4.06 (3 H, s), 4.20 (3 H, s), 4.62 (3 H, s), 7.42 (2 H, d, J = 8Hz), 7.61 (1 H, s), 7.76 (3 H, m), 9.09 (1 H, s), 9.28 (1 H, s). ¹³C NMR (75 MHz, MeOD): δ = 26.7, 51.7, 62.4, 63.3, 130.7, 113.6, 130.8, 132.3, 136.5, 143.7, 143.9, 144.8, 145.5, 146.6, 149.4, 158.6, 165.2. ¹⁹F NMR (282 MHz, CDCl₃): δ = - 80.25. HRMS: m/z calcd for C₁₉H₂₀NO₃S: 342.1164. Found: 342.1165.

16

Analytical data for (R)-1b: ¹H NMR (300 MHz, CDCl₃): δ = 2.32 (3 H, s), 2.94 (1 H, d, J = 18 Hz), 3.17 (3 H, s), 3.63 (1 H, d, J = 18 Hz), 3.67 (3 H, s), 3.78 (3 H, s), 6.24 (1 H, s), 6.33 (1 H, s), 6.84 (1 H, s), 7.21 (2 H, d, J = 8Hz), 7.43 (2 H, d, J = 8Hz). ¹³C NMR (75 MHz, CDCl₃): δ = 21.8, 21.9, 39.2, 56.5, 56.6, 98.6, 108.5, 113.1, 113.4, 125.4, 130.0, 132.7, 139.2, 140.6, 140.9, 154.2, 148.3. HRMS (CI):
m/z calcd for C₁₉H₂₁NO₃S: 343.1242. Found: 343.1249.

17

Typical Procedure for the Reduction of Methyl Benzoylformate with Mimics 1a,b:
In a flask, flushed with argon, were introduced model 1b (0.283 g, 1 mmol), MeCN (3 mL), methyl benzoylformate (142 µL, 1 mmol) and Mg(ClO₄)₂ (224 mg, 1 mmol). The resulting solution was stirred at r.t. for 24 h in the dark. After addition of H₂O (10 mL), the organic solvent was evaporated under reduced pressure and the resulting aqueous phase was extracted with CH₂Cl₂ (3 × 10 mL). After drying (MgSO₄) and evaporation of the solvent, the residue was purified by chromatography on silica gel (eluent: Et₂O-cyclohexane = 2:1). Yield: 50%. Enantiomeric excesses were determined by HPLC analysis using a Chiracel OD column (250 × 4.6 mm; 10 µm). Chromatographic conditions: injection: 20 µl (0.5 mg of methyl mandelate in 10 mL of hexane); eluent: hexane-2-propanol = 90:10; flow rate: 1 mL min^-1; pressure: 300 psi; temperature: 22 °C; UV detection: λ = 235 nm; t _R = 9.2 min [(S)-enantiomer] and 14.8 min [(R)-enantiomer].