2-Ethylhexanol 104-76-7

1. Synthesis of 2-Ethyl-2-hexenal Add 30 g (0.42 mol) of butyraldehyde to a 250 mL three-neck flask, a 5% sodium hydroxide solution (15 mL), and ethanol (50 mL). Stir the mixture in a water bath at 40°C overnight. Monitor the reaction by thin-layer chromatography (TLC).

Remove the ethanol by rotary evaporation. Extract the mixture three times with 100 mL of ethyl acetate, combine the organic layers, wash with distilled water, rinse with brine, dry with anhydrous magnesium sulfate, filter and evaporate to dryness, yielding a pale yellow transparent liquid (13.8 g, 52% yield).

2. Synthesis of 2-ethyl-2-hexen-1-ol Add 2-ethyl-2-hexenal (5 g, 40 mmol), sodium borohydride (3 g, 80 mmol), and anhydrous methanol (20 mL) to a 100 mL three-neck flask.

Stir at room temperature for 3 hours. Add 10 mL of pure water under ice bath conditions, extract with ethyl acetate, combine the organic layers, wash with pure water, wash with saturated brine, dry with anhydrous magnesium sulfate, filter, spin-dry, and purify by column chromatography to obtain a colorless transparent liquid (4.36 g), yield: 85%.

3. Synthesis of (S)-2-ethylhexanol Under a nitrogen atmosphere, add the biphasic ligand ChenPhos (3.28 mg, 0.0021 mmol), Rh(NBD)₂BF₄ (1.50 mg, 0.002 mmol), and dichloromethane (2 mL) into a 10 mL reaction vessel under a nitrogen atmosphere, stirred for 30 minutes, yielding a yellow, clear solution, which serves as the catalyst.

Add 2-ethyl-2-hexenol (25.6 mg, 0.2 mmol), then place the inner tube in a hydrogenation reactor. Perform three hydrogenation and degassing operations to replace the atmosphere with hydrogen, then pressurize to 50 atm and stir at room temperature for 20 hours. Stop the reaction, release the gas, and concentrate the reaction mixture by rotary evaporation. Filter through a silica gel column to obtain a colorless oily liquid (25.2 mg), with a yield of 97% and 98.3% ee.