Recyclable Siloxy Serine Organocatalyst for the Direct Asymmetric Mannich Reactions in Ionic Liquids

Abstract

A recyclable siloxy-L-serine organocatalyst has been developed to catalyze the asymmetric direct three-component Mannich reactions in ionic liquid hmim[PF₆], furnishing the β-amino carbonyl scaffold in high enantio- and diastereoselectivities. The direct Mannich reaction between a selection of aromatic aldehydes and ketones resulted in good yields and high enantioselectivities.

Keywords:

• β-Amino carbonyl compounds
• asymmetric Mannich
• enantiomeric excess
• organocatalyst
• serine

ACKNOWLEDGMENT

We thank the National Institute of Education (RP05/06 TYC), Nanyang Technological University, for their generous financial support.

Notes

^a Unless otherwise noted, the reaction was performed with aldehyde (0.5 mmol), ketone (cyclohexanone: 1.5 mmol, O-benzyl hydroxyacetone: 1.35 mmol), p-anisidine (0.45 mmol), and catalyst (0.045 mmol) in hmim[PF₆] (0.5 mL) at room temperature for 14 h.

^b Combined yield of isolated diastereomers.

^c Diastereoselectivity was determined by ¹H NMR analysis of the reaction mixture.

^d Enantiomeric excess refers to the major isomer and was determined by HPLC analysis on a chiral phase.

^e The reaction was performed for 38 h.

^a Unless otherwise noted, the reaction was performed with 4-nitrobenzaldehyde (0.5 mmol), cyclohexanone (1.5 mmol), p-anisidine (0.45 mmol), and catalyst (0.045 mmol) in hmim[PF₆] (0.5 mL) at room temperature.

^b Combined yield of isolated diastereomers.

^c Diastereoselectivity was determined by ¹H NMR analysis of the reaction mixture.

^d Enantiomeric excess refers to the syn isomer and was determined by HPLC analysis on a chiral phase.