Proline-Catalyzed Asymmetric Direct Aldol Reaction Assisted by d-Camphorsulfonic Acid in Aqueous Media

Abstract

Asymmetric aldol reactions of aromatic aldehydes with various ketones catalyzed by l-proline with d-camphorsulfonic acid as co-catalyst have been developed in aqueous media. High reactivity and modest to excellent enantioselectivity has been achieved.

asymmetric direct aldol reaction - co-catalyst - proline - camphorsulfonic acid - aqueous media

References

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12

Typical Procedure (Table [1] , entry 3): Anhyd acetone (2.0 mL, dried with K₂CO₃ before use) was added to p-nitro-benzaldehyde (75 mg, 0.5 mmol), followed by l-proline (20 mol%) and d-CSA (10 mol%) dissolved in water (0.5 mL). The resulting mixture was stirred at r.t. for 12 h. After treating the reaction mixture with saturated aq NaHCO₃ (5 mL), the aqueous layer was separated, and extracted with EtOAc three times. The combined organic extracts were washed with brine (5 mL), dried over anhyd Mg₂SO₄, and concentrated. The residue was purified by preparative thin layer chromatography (Silica gel plates GF254, hexane-EtOAc) to give the aldol product (76.3 mg). The anti/syn ratio is established by ¹H NMR; d = 4.83 ppm (J = 9.0 Hz) - CH of the anti-isomer; 5.42 ppm (J = 2.7 Hz) - CH of the syn-isomer (Table [4] , entry 1). The ee values were determined by HPLC, Daicel chiralpak AS-RH.

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