Heteroarenesulfonyl Cinchona Alkaloid Amine Catalyst

Nakamura et al. have reported development of the heteroarenesulfonyl cinchona alkaloid amine catalyst,
N-[(9S)-8α-cinchonan-9-yl]quinoline-8-sulfonamide (1), and its use for the enantioselective decarboxylative Mannich reaction of ketimines. According to their results, the reaction of ketimines with malonic acid half thioesters in the presence of 1 affords the corresponding β-aminocarbonyl compounds with high enantioselectivity. Since β-aminocarbonyl compounds are important backbones of pharmaceuticals and agricultural chemicals, they can be converted into biologically active substances, such as optically active AG-041R.

Typical Procedure (Entry 1):
To a solution of ketimine (0.038 mmol, 10.0 mg) and 1 (0.008 mmol, 3.9 mg) in CPME (0.5 mL), malonic acid half thioester (0.084 mmol, 16.4 mg) is added and stirred for 48 h. After removal of solvent, the residue is purified by silica gel column chromatography (hexane : AcOEt = 80 : 20) to afford the (S)-product (14.3 mg, Y. 91%) as a white solid.