Heteroarenecarbonyl Cinchona Alkaloid Catalysts

Nakamura et al. have developed the heteroarenecarbonyl cinchona alkaloid catalysts 1, and reported the enantioselective desymmetrization of aziridines with phosphites using 1.¹⁾ According to their results, various aziridines are converted into optically active β-aminophosphonic acids in high yields with high enantioselectivities by using 1 and Et₂Zn as catalysts. In this approach, both enantiomers are directly synthesized by using either 1a and 1b. Obtained optically active β-aminophosphonic acids and their derivatives can be used as biologically active substances and chiral ligands.

Nakamura et al. have also reported the cinchona alkaloid amide/copper(II) catalyzed diastereo- and enantioselective vinylogous Mannich reaction of ketimines.²⁾ This article has been chosen as a "Hot Paper" by the editors of "Angewandte Chemie" for its importance.

Typical Procedure: Enantioselective Desymmetrization of Aziridines with Phosphites (Entry 1)
MS 5Å (100 mg) and Na₂CO₃ (32 mg, 0.30 mmol) are heated with heat-gun, and it is heated at 140 °C under reduced pressure for 1 h. To a suspension of 1a (8.0 mg, 0.02 mmol), MS 5Å and Na₂CO₃ in benzene (1.0 mL) is added Et₂Zn (1.0 M in toluene, 20 μL, 0.02 mmol) and stirred for 10 min. A solution of aziridines (0.20 mmol) and diphenyl phosphite (58 μL, 0.30 mmol) in benzene (0.5 mL) is added to the reaction mixture and is stirred for 12 h. Then the reaction mixture is diluted with AcOEt and filtered through a celite pad. The volatile compounds are removed under reduced pressure and the crude product is purified by silica gel column chromatography (Hexane : AcOEt=1 : 1) to give the desired (R,R)-product. The (S,S)-product is obtained by using 1b instead of 1a.