Metal-Free Brønsted Acid Catalyzed Transfer Hydrogenation - New Organocatalytic Reduction of Quinolines

Abstract

The first metal-free Brønsted acid catalyzed hydrogenation of quinolines using Hantzsch dihydropyridine as the hydrogen source has been developed. This, so far unprecedented organocatalytic reduction of heteroaromatic compounds provides a variety of differently substituted 1,2,3,4-tetrahydroquinolines in excellent yields under mild reaction conditions using a remarkably low amount of Brønsted acid catalyst.

Brønsted acid - Hantzsch dihydropyridine - transfer ­hydrogenation - organocatalysis - reduction - 1,2,3,4-tetrahydro­quinoline

References and Notes

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8

General Procedure for the Brønsted Acid Catalyzed Transfer Hydrogenation of Quinolines.
In a typical experiment quinoline (20 mg), diphenyl phosphate (1 mol%) and Hantzsch dihydropyridine 2 (2.4 equiv) were suspended in benzene (2 mL) in a screw-capped vial and flushed with argon. The resulting mixture was allowed to stir at 60 °C for 12 h. The solvent was removed under reduced pressure and purification of the crude product by column chromatography on silica gel afforded the pure 1,2,3,4-tetrahydroquinoline. For representative examples, see:
7-Chloro-1,2,3,4-tetrahydro-4-phenylquinoline (6o): yield 19.3 mg, 94%. IR (KBr): 3412, 3396, 2919, 1604, 1492, 1089, 700 cm^-1. ¹H NMR (250 MHz, CDCl₃): δ = 1.88-2.18 (m, 2 H, C-3H), 3.08-3.28 (m, 2 H, C-2H), 3.94 (br s, 1 H, NH), 4.01 (t, J = 6.1 Hz, 1 H, C-4H), 6.39-6.48 (m, 2 H, Ar), 6.56-6.59 (m, 1 H, Ar), 6.99-7.07 (m, 2 H, Ar), 7.09-7.27 (m, 3 H, Ar). ¹³C NMR (250 MHz, CDCl₃): δ = 30.7, 38.9, 42.4, 113.4, 116.8, 121.7, 126.3, 128.4, 128.6, 131.5, 132.6, 145.9, 146.0. MS-ESI: m/z = 243.8 [M⁺], 245.8 [M⁺]. Anal. Calcd for C₁₅H₁₄ClN (243.73): C, 73.92; H, 5.79; N, 5.75. Found: C, 73.69; H, 5.54; N, 5.74.
1,2,3,4-Tetrahydro-4,7-diphenylquinoline (6p): yield 18.6 mg, 91%. IR (KBr): 3356, 3292, 3024, 2945, 2924, 1562, 1485, 1468, 1319, 758, 698 cm^-1. ¹H NMR (250 MHz, CDCl₃): δ = 1.93-2.27 (m, 2 H, C-3H), 3.13-3.34 (m, 2 H, C-2H), 3.96 (br s, 1 H, NH), 4.10 (t, J = 6.1 Hz, 1 H, C-4H), 6.69-6.73 (m, 3 H, Ar), 7.10-7.38 (m, 8 H, Ar), 7.45-7.50 (m, 2 H, Ar). ¹³C NMR (250 MHz, CDCl₃): δ = 31.2, 39.4, 42.7, 112.7, 116.2, 122.7, 126.2, 127.0, 128.4, 128.6, 128.7, 130.8, 140.4, 141.5, 145.2, 146.5. MS-ESI: m/z = 285.8 [M⁺]. Anal. Calcd for C₂₁H₁₉N (285.38): C, 88.38; H, 6.71; N, 4.91. Found: C, 88.11; H, 6.80; N, 4.79.

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10 An extension of this procedure to an asymmetric variant by employing a chiral phosphate catalyst has been achieved: Rueping M. Antonchick AP. Theissmann T. Angew. Chem. Int. Ed.  2006,  45:  in press