Enantioselective aza-Henry reaction for the synthesis of (S)-levamisole using efficient recyclable chiral Cu(II)–amino alcohol derived complexes

• In situ generated chiral complex L2–Cu(II) was employed in asymmetric aza-Henry reaction.
• Several protected aldimines with nitroalkanes were used as substrate for aza-Henry reaction at RT.
• Chiral Schiff base complex was highly recyclable with retention of its activity and ee.

Chiral Cu(II) complexes were generated in situ by the interaction of aminoalcohol based ligands L1–L6 derived from (1R,2S)-(−)-2-aminodiphenylethanol, (1R,2S)-1-amino-2,3-dihydro-1H-inden-2-ol, (R or S)-valinol and (S)-2-amino-1,1-diphenylpropan-1-ol with 4-tert-butyl-2,6-diformylphenol and screened for aza-Henry reaction of a variety of aromatic, aliphatic N-tosylaldimine and aromatic N-benzenesulfonamide aldimine in toluene at RT. Excellent enantioselectivity, diastereoselectivity (99%) of β-nitro-N-tosylaldamine with good yield (80%) was achieved in case of complex L2–Cu(II) with low catalyst loading. The enantio-pure aza-Henry product obtained was straightforwardly transformed into the enantioenriched chiral vicinal diamine (ee; 96%) with good yield in successive two steps and was further used for the synthesis of (S)-levamisole (an anthelminthic agent). The catalytic system worked well up to five cycles with retention of enantioselectivity.

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