Asymmetric Henry reactions catalyzed by metal complexes of chiral oxazoline based ligands

Chiral oxazolines have been synthesized from norephedrine and pyrrole nitrile or benzoyl chloride and applied to the catalytic asymmetric Henry reactions of p-nitro aldehydes with nitromethane to provide β-hydroxy nitroalkanols in high conversion (up to 92%). The reaction was then optimized in terms of the metal, solvent, temperature, and amount of chiral ligand. The corresponding catalyst with Cu(OTf)2 and isopropanol as the solvent gave the best enantioselectivities (up to 84% ee) of the corresponding β-nitroalkanol for p-nitrobenzaldehyde.

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(4S,5R)-4-Methyl-5-phenyl-2-(1H-pyrrol-2-yl)-4,5-dC13H14N2O[α]D20=-322 (c 1.94, CHCl3)Source of chirality: (1R,2S)-norephedrineAbsolute configuration: (4S,5R)

2-((4S,5R)-4,5-Dihydro-4-methyl-5-phenyloxazol-2-yl)phenolC16H15NO2[α]D20=+67.1 (c 0.149, CHCl3)Source of chirality: (1R,2S)-norephedrineAbsolute configuration: (4S,5R)