Synthesis of Chiral Diamine Ligands for Nickel-catalyzed Asymmetric Cross-couplings of Alkylchloroboronate Esters with Alkylzincs: (1R,2R)-N,N’-Dimethyl-1,2-bis(2-methylphenyl)-1,2-diaminoethane

Abstract

A. (1R,2R)-N,N'-Bis(2-hydroxyphenylmethylene)-1,2-bis(2-methylphenyl)-1,2-diaminoethane (1). An oven-dried, 100-mL, two-necked, round-bottomed flask equipped with a magnetic stir bar (13 × 9 mm, octagon-type), a rubber septum, and a nitrogen line is evacuated under high vacuum (1.0 mmHg) and filled with nitrogen (three cycles). (1S,2S)-1,2-Bis(2-hydroxyphenyl)-1,2-diaminoethane (1.0 g, 4.1 mmol, 1.0 equiv) (Note 2) is added through the open neck under a positive pressure of nitrogen. The open neck is capped with a rubber septum, and then anhydrous DMSO (20 mL) (Note 3) and 2-methylbenzaldehyde (1.23 g, 10.2 mmol, 2.5 equiv) (Note 4) are added into the flask by syringe through the rubber septum. After the yellow solution (Figure 1) is stirred for 14 h at 20 °C, the reaction is quenched by the addition of distilled water (100 mL), and the mixture is extracted with Et₂O (20 mL × 3). The combined organic layer is washed with water (30 mL) and a saturated aqueous solution of NaCl (30 mL), dried over anhydrous Na₂SO₄ (5 g), filtered through filter paper, and concentrated by rotary evaporation (30 mmHg, 30 °C) and under vacuum (1.0 mmHg). The product, obtained as a yellow oil as a mixture with unreacted 2-methylbenzaldehyde, is used in the next step without further purification (2.2 g, ~98% yield) (Note 5).