A Simple Protocol for Direct Reductive Amination of Aldehydes and Ketones Using Potassium Formate and Catalytic Palladium Acetate

Abstract

A method for direct reductive amination of aldehydes and ketones, including α,β-unsaturated carbonyl compounds, has been developed, which requires potassium formate as reductant and palladium acetate as catalyst. Suitable amines include both primary and secondary aliphatic and aromatic amines.

Key words

reductive amination - potassium formate - palladium acetate - one-pot reaction

References

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17

General Procedure for Aldehydes. For the aldehydes (listed in Table [1] ) except cinnamaldehyde:
A solution of p-anisaldehyde (680 mg, 5 mmol) and cyclohexylamine (500 mg, 5 mmol) in dry DMF (5 mL) was magnetically stirred at r.t. for 4 h, in presence of molecular sieves (4 Å). To the resulting reaction mixture were added HCOOK (840 mg, 10 mmol) and palladium acetate (22 mg, 0.1 mmol). The mixture was then heated at 40 °C for 3 h to complete the reaction (TLC) and after cooling it was diluted with ice-cold water (15 mL). The mixture was extracted with ether (3 × 20 mL). The combined extract was washed with brine, dried (Na₂SO₄), and evaporated to leave the crude product, which was purified by column chromatography over silica gel. Elution with ethyl acetate-hexanes (1:19; R_f 0.26) furnished N-cyclohexyl p-methoxybenzyl amine 4 (815 mg, 75%) as an oil: IR(neat): 1246, 1300, 1510, 1610, 2851, 2925 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.05-1.31 (m, 6 H), 1.61 (br, 1 H), 1.70-1.92 (m, 4 H), 2.43-2.50 (m, 1 H), 3.73 (s, 2 H), 3.78 (s, 3 H), 6.84 (d, 2 H, J = 8.3 Hz), 7.22 (d, 2 H, J = 8.3 Hz). ¹³C NMR (75 MHz, CDCl₃): δ = 24.9, 26.2, 33.4, 50.3, 55.2, 56.0, 113.7, 129.2, 132.9, 158.4.