Organocatalytic, Asymmetric, One-Pot, Three-Component Mannich Reaction of Hydroxyacetone

Abstract

The direct three-component asymmetric Mannich reactions of hydroxyacetone with anilines and aromatic aldehydes in the presence of (2S,5S)-5-(methoxycarbonyl)pyrrolidine-2-carboxylic acid afforded syn-1,2-amino alcohols in good-to-excellent yields (55∼91%) and up to 98% ee.

Keywords:

• Amino alcohol
• asymmetric Mannich reaction
• enantioselectivity
• hydroxyacetone
• organocatalysis

ACKNOWLEDGMENT

We thank the National Natural Science Foundation of China (20402004) and the Science Foundation of Shanghai Municipality (06ZR14028) for financial support.

Notes

^a Isolated yield after silica-gel column chromatography.

^b Determined by HPLC analysis.

^c Ee values of syn-isomer, determined by HPLC using chiralpak AD-H column.

^d 4 Å Molecular sieves were added.

^e The reaction was carried out at 10 °C.

^f Performed imine was used.

^a Isolated yield after column chromatography.

^b Determined by HPLC analysis.

^c Enantiomeric excess of syn-product was determined by HPLC using Chiralcel OD-H or Chiralpak AD-H column.

^a Isolated yield after silica-gel column chromatography.

^b Determined by HPLC analysis.

^c Ee values of syn-isomer, determined by HPLC using Chiralpak AD-H column.