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

All articles of this category

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

Full Text

References

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

<A NAME="RD34304ST-1A">1a</A> Li J. Liu Y.-C. Deng J.-G. Tetrahedron: Asymmetry 1999, 10: 4343

<A NAME="RD34304ST-1B">1b</A> Kazuyuki M. Nishimoto N. Hidenobu M. Asuka M. Satoshi O. Yasuko I. Toshimasa I. Takeshi I. Chem. Commun. 1996, 2535

<A NAME="RD34304ST-1C">1c</A> Obika S. Nishiyama T. Tatematsu S. Miyashita K. Iwata C. Imanishi T. Tetrahedron 1997, 53: 593

<A NAME="RD34304ST-1D">1d</A> Obika S. Nishiyama T. Tatematsu S. Miyashita K. Imanishi T. Chem. Lett. 1996, 853

<A NAME="RD34304ST-1E">1e</A> Obika S. Nishiyama T. Tatematsu S. Nishimoto M. Miyashita K. Imanishi T. Heterocycles 1998, 261

<A NAME="RD34304ST-1F">1f</A> 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:

<A NAME="RD34304ST-2A">2a</A> Levacher V. Dupas G. Quéguiner G. Bourguignon J. Trends Heterocycl. Chem. 1995, 4: 293

<A NAME="RD34304ST-2B">2b</A> Dupas G. Levacher V. Quéguiner G. Bourguignon J. Heterocycles 1994, 39: 405

<A NAME="RD34304ST-2C">2c</A> Vitry C. Vasse J.-L. Levacher V. Dupas G. Quéguiner G. Bourguignon J. Tetrahedron 2001, 57: 3087

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.

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].

<A NAME="RD34304ST-5A">5a</A> Dumouchel S. Mongin F. Trécourt F. Quéguiner G. Tetrahedron Lett. 2003, 44: 2033

<A NAME="RD34304ST-5B">5b</A> Dumouchel S. Mongin F. Trécourt F. Quéguiner G. Tetrahedron 2003, 44: 8629

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.

<A NAME="RD34304ST-7">7</A> 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

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.

<A NAME="RD34304ST-9">9</A> Charpentier P. Lobrégat V. Levacher V. Dupas G. Quéguiner G. Bourguignon J. Tetrahedron Lett. 1998, 39: 4013

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.

<A NAME="RD34304ST-11">11</A> Smith AB. Levenberg PA. Jerris PJ. Scarborough RM. Wovkulich PM. J. Am. Chem. Soc. 1981, 103: 1501

<A NAME="RD34304ST-12">12</A> Trofimenko S. J. Org. Chem. 1963, 28: 3243

<A NAME="RD34304ST-13">13</A> 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.

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].

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.

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.

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].