Transformation of α-Substituted Propanols into γ-Amino Alcohols through Nickel-Catalyzed Amination on the Terminal γ-Carbon of Propanols

Abstract

A nickel-phosphine complex was found to be effective as the catalyst for the transformation of alcohols into β-enaminones, which was successively converted into γ-amino alcohols by a conventional reductant. The sequential transformation is equivalent to the carbon-nitrogen bond formation at the γ-position of saturated alcohols.

Key words

nickel - alcohols - amination - amino alcohols - oxidation

References and Notes

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• 16 The compound 3n was characterized as the Z-isomer by an observing of the small coupling constant (J = 7.5 Hz) between two vinyl protons; see supporting information for details. The ^¹H NMR and ^¹³C NMR spectroscopic data are in agreement with the previously reported literature, see: Haak E. Eur. J. Org. Chem.  2007,  2815 

11

Typical Procedure for the Transformation of 1a into 3a: In a nitrogen-filled drybox, a 4-mL screw-capped vial was charged with Ni(cod)₂ (5.5 mg, 0.02 mmol), K₃PO₄ (636.8 mg, 3.0 mmol), and dioxane (0.3 mL). After a magnetic stir bar was added, the vial was fitted with a septum cap, and removed from the drybox. A solution of trimethylphosphine (60 µL, 1 M THF solution, 0.06 mmol), chlorobenzene (0.3 mL, d 1.106 g/mL, 2.95 mmol), morpholine (2a), and 1-phenyl-1-propanol (1a) was added. The resulting mixture was heated at 100 ˚C. The progress of the reaction was confirmed by GC analysis. After complete consumption of the starting material, the reaction mixture was quenched with H₂O (1 mL) and extracted with EtOAc (3 × 1 mL). The organic layer was concentrated, and purified by silica gel column chromatography (hexane-EtOAc = 3:1 → 1:8), which gave the β-enaminone 3a (92.9 mg, 86%) as a pale yellow solid. ^¹H NMR (400 MHz, CDCl₃, TMS): δ = 3.27-3.53 (m, 4 H), 3.63-3.93 (m, 4 H), 5.88 (d, J = 12.6 Hz, 1 H), 7.33-7.56 (m, 3 H), 7.74 (d, J = 12.6 Hz, 1 H), 7.83-8.00 (m, 2 H). ^¹³C{^¹H} NMR (100 MHz, CDCl₃): δ = 48.3 (br s), 66.2, 92.4, 127.4, 128.1, 131.1, 140.1, 152.7, 189.1.

14

We previously demonstrated that the dehydrogenation of β-amino ketones is faster than that of ethyl ketones, see: ref. 5.