Highly Selective Reductive Cross-Amination between Aniline or Nitroarene Derivatives and Alkylamines Catalyzed by Polysilane-Immobilized Rh/Pt Bimetallic Nanoparticles

Published as part of the 30 Years SYNLETT – Pearl Anniversary Issue

Abstract

Reductive cross-amination between imine intermediates generated through partial hydrogenation of aniline or nitroarene derivatives and alkylamines is an ideal method for obtaining N-alkylated cyclohexylamine derivatives; however, no such transformations have hitherto been established. Here, we report a highly selective reductive cross-amination using aniline derivatives and alkylamines catalyzed by heterogeneous Rh/Pt bimetallic nanoparticles under mild conditions. The catalyst was recovered and reused for five runs, keeping high activity. In this reaction, imine intermediates generated during the course of partial hydrogenation of aniline derivatives were trapped immediately by strongly interacting primary alkylamines with the catalyst, which caused a highly selective transformation to give the desired products, while suppressing dicyclohexylamine formation.

Key words

reductive amination - arene hydrogenation - heterogeneous catalyst - metal nanoparticle

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• 11 Rh-Pt/(DMPSi-Al₂O₃) (33.4 mg, 0.75 mol% as Rh), n-octylamine (1a) (51.7 mg, 0.4 mmol) and aniline (2a) (74.0 mg, 0.8 mmol) were placed in a Caroucel^® tube. The atmosphere was exchanged to H₂ using a balloon and pump. The reaction mixture was stirred at 50 °C for 24 h, then the reaction was quenched by the addition of EtOAc (5 mL) and the reaction mixture was analyzed by GC using decane as internal standard. Yield: 93%; GC flow rate (157.5 kPa, He), Inject (50 °C), Detect (100 °C), Int. T (50 °C), Int. T (0 min), Rate (5 °C/min), Fin. T (100 °C), Fin. T (10 min): t_R = 30.068 (N-n-octylcyclohexylamine), 19.304 (decane internal standard) min.
• 12 Rh-Pt/(DMPSi-Al₂O₃) (81.2 mg, 0.75 mol% as Rh), 3-methoxypropylamine (1d) (176.7 mg, 1.2 mmol) and aniline (2a) (279.4 mg, 3.0 mmol) were placed in a Caroucel^® tube. The atmosphere was exchanged to H₂ using balloon and pump. After the reaction mixture was stirred at 50 °C for 38 h, the reaction was quenched by the addition of CH₂Cl₂ (5 mL). The catalyst was filtered off and the filtrate was concentrated. The desired product was isolated from the crude mixture by column chromatography (hexane/EtOAc/Et₃N = 3:2:0.1). Yield: 97%; ¹H NMR (600 MHz, CDCl₃): δ = 3.44 (t, J = 6.2 Hz, 2 H), 3.32 (s, 3 H), 2.71 (t, J = 6.9 Hz, 2 H), 2.44–2.39 (m, 1 H), 1.87 (d, J = 13.0 Hz, 2 H), 1.77–1.70 (m, 4 H), 1.63–1.59 (m, 1 H), 1.42 (br, 1 H), 1.29–1.21 (m, 2 H), 1.19–1.14 (m, 1 H), 1.09–1.03 (m, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 71.4, 58.6, 56.9, 44.3, 33.6, 30.4, 26.2, 25.1. IR (neat): 3579, 3312, 2928, 2853, 1672, 1454, 1375, 1304, 1255, 1195 cm^–1. HRMS (DART): m/z [M+H]⁺ calcd for C₁₀H₂₂NO⁺: 172.17014; found: 172.16781.