A Practical Synthesis of C2-Symmetric Chiral Binaphthyl Ketone Catalyst

Several Recommendations for Improved Synthesis



A practical synthesis of 11-membered C2-symmetric binaphthyl ketone (R)-1, a catalyst for asymmetric epoxidation, was developed. This manuscript describes the single example of chiral resolution of (±)-1,1’-Binaphthyl-2,2’-dicarboxylic acid [(±)-6].

The Reaction of Interest:

Chiral resolution of (±)-1,1’-Binaphthyl-2,2’-dicarboxylic acid using (R)-(-)-1-cyclohexylethylamine (38%, 30 mmol scale).

" To a suspension of (±)-6 (10.3 g, 30 mmol) in MeOH (22 mL) were added Me2NH (50 wt% solution in H2O, 2.44 g, 27 mmol) and (R)-CHEA (4.58 g, 36 mmol) and the mixture was dissolved at 65 °C. To this mixture was added boiling water (50 mL) and the mixture was gradually cooled down to 25 °C under mechanical stirring for 2.5 h. After further stirring at 25 °C for 1 h, the crystals formed were collected, washed with 40% MeOH/H2O (20 mL) and dried at 60 °C for 5 h to give (R)-6•[( R)-CHEA]2 (6.85 g) as colorless crystals. The salt (R)-6•[(R)-CHEA]2 (6.85 g, 11.5 mmol) was dissolved in 1 N aq NaOH solution (25.3 mL, 25.3 mmol) and washed with CH2Cl2 (2 × 5 mL). The aqueous layer was acidified by concd HCl and extracted with EtOAc (20 mL). The organic layer was washed with H2O, treated with active charcoal (0.1 g), dried (MgSO4) and evaporated. The crystals formed were dried at 90 °C for 17 h to provide (R)-(3.91 g, 38%) in colorless crystals."

-- According to the described procedure (R)-1,1’-Binaphthyl-2,2’-dicarboxylic acid was prepared in 28% yield (5 mmol scale).

Practical Observations:

  • The separation procedure is not well reproducible (on smaller scale), and yield of the chiral acid is lower than described (28%, 5 mmol scale).


  • The acid/chiral amine salt is not soluble in the reaction mixture at 65 oC (the yellow oil is formed). A larger amount of methanol is required to dissolve the material at 65 oC (~10 mL of MeOH for 5 mmol scale).
  • The same amount of boiling water (8.3 mL for 5 mmol scale) was added, and the reaction mixture was gradually cooled down to 25 °C under stirring for 2.5 h (no solid precipitate).
  • Methanol (~ 5 mL) was evaporated from the reaction mixture (in vacuo).
  • The precipitate of the acid/chiral amine salt was formed upon stirring of the residue solution at 5 °C for 24 h.
  • Further treatment of the salt according to the procedure led to the isolation of (R)-1,1’-Binaphthyl-2,2’-dicarboxylic in 28% yield (99% ee according to HPLC, Chiralcel OD (Daicel), hexane/EtOH/trifluoroacetic/acid = 90:10:0.1, 1 mL/min, 25 °C, 254 nm).

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