Brønsted Acid Catalysis: Organocatalytic Hydrogenation of Imines

Abstract

A new Brønsted acid catalysed hydrogenation of imines with Hantzsch dihydropyridine as the hydrogen source has been ­developed. Diphenyl phosphate (DPP) and various other acids ­catalyse this first metal-free hydrogen transfer to give various amines under mild reaction conditions.

Key words

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

References

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9

General Procedure for the Acid-Catalysed Transfer Hydrogenation.
In a typical experiment the imine 1, diphenyl phosphate (5 mol%) and Hantzsch dihydropyridine 2 (1.4 equiv) were suspended in CH₂Cl₂ in a screw-capped vial and flushed with argon. The resulting mixture was allowed to stir at 40 °C for 10 h. The solvent was removed under reduced pressure and purification of the crude product by column chromatography on silica gel afforded the pure amine 4. Representative example: according to the general procedure, imine 1n (0.3 mmol) was transformed to amine 4n (62.6 mg, 77%). ¹H NMR (250 MHz, CDCl₃): δ = 3.62 (s, 3 H, OMe), 3.64 (s, 3 H, OMe), 4.58 (br s, 1 H, NH), 4.94 (br s, 1 H, CH), 6.42-6.48 (m, 2 H, Ar), 6.61-6.67 (m, 2 H, Ar), 7.20-7.43 (m, 5 H, Ar). ¹³C NMR (250 MHz, CDCl₃): δ = 52.7, 55.7, 61.6, 114.8 (2×), 114.9 (2×), 127.3 (2×), 128.3, 128.9 (2×), 137.8, 140.2, 152.5, 172.5. IR (KBr): 3420, 1730, 2360, 1510, 1320, 1240 cm^-1. MS-ESI: 272 [M + H]⁺, 213 [M - CO₂Me]⁺. Anal. calcd for C₁₆H₁₇NO₃ (271.12): C, 70.94; H, 6.54; N, 5.17. Found: C, 70.83; H, 6.32; N, 5.17.