Direct Amination of Benzylic Pinacol Boronates by an Aminoazanium

Abstract

A practical stereospecific direct amination of benzylic pinacol boronates was achieved by using 4-amino-4-methylmorpholinium iodide as a new amination reagent and cesium carbonate as the base. After amination, an in situ reductive N-alkylation with an aldehyde proceeded well to produce secondary amines.

Key words

benzylic pinacol boronates - amination - asymmetric synthesis - secondary amines - aminomethylmorpholinium iodide

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• 20 Compounds 2a–ab; General Procedure An oven-dried Schlenk tube was charged with the appropriate boronate (0.2 mmol), H₂N-NMM (68.3 mg, 1.4 equiv), and Cs₂CO₃ (91.2 mg, 1.4 equiv), then purged with N₂. Anhyd toluene (2 mL) was added and the mixture was stirred at 100 °C for 10 h. A 1 M solution of Boc₂O in THF (2.0 equiv) was added and the mixture was heated at 80 °C for 1 h. The reaction was quenched with EtOAc, and the mixture was concentrated under a vacuum. The residue was purified by flash column chromatography [silica gel, PE–EtOAc (10:1)]. Visualization was performed by using ninhydrin. tert-Butyl (1-phenylethyl)carbamate (2a) White solid; yield: 36.2 mg (82%). ¹H NMR (400 MHz, CDCl₃): δ = 7.36–7.22 (m, 5 H), 4.79 (br s, 2 H), 1.53–1.21 (m, 12 H). ¹³C NMR (101 MHz, CDCl₃): δ = 155.2, 144.1, 128.7, 127.2, 126.0, 79.5, 50.3, 28.5, 22.8.