The asymmetric Mannich reaction of 3-fluorooxindoles and α-amidosulfones catalyzed by a chiral urea catalyst derived from quinine in presence of K3PO4 was developed. Through the asymmetric reaction, a series of α-fluoro-β-amino-oxindoles, containing a tertiary carbon stereocenter, could be obtained in high yields (up to 95%) with high enantioselectivity (95%) and diastereoselectivity (>99:1). Such α-fluoro-β-amino-oxindole compounds are expected to become candidates in the field of medicine.
20 To a stirred solution of isatin (1 mmol) in 5 mL methanol, hydrazine hydrate (1.5 mmol) was added over 6 h at 75 ℃. After concentrated under reduced pressure, it was next purified by flash chromatography using DCM to obtain the desired isatin hydrazone products.
Next, LiOAc (5 mmol) and Selectfluor (2 mmol) were added into the isatin hydrazone (1 mmol) in DCE and stirred at 80 ℃ for 16 h. The reaction mixture was extracted with EtOAc (3 × 5 mL), dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude mixture was next purified by flash chromatography using hexane/EtOAc (8:1) to obtain product 1.
