Enantioselective catalysts for the Henry reaction: fine-tuning the catalytic components

Abstract

Catalysts for the asymmetric Henry reaction involving 1,6-bis(3-ethoxy-2-hydroxyphenyl)-(3S,4S)-(−)-diphenyl-2,5-diazahexane (H₂2) and copper salts have been investigated. Conditions for the conversion of 4-nitrobenzaldehyde to 2-nitro-1-(4-nitrophenyl)ethanol by reaction with nitromethane have been optimized (5 mol% H₂2, 10 mol% CuI, THF, 295 K and 2 hours or 273 K and 12 hours) resulting in 99% yield and 90–92% ee. These catalytic conditions are effective for other aromatic aldehydes containing electron-withdrawing substituents, and for pyridine carbaldehydes; representative aliphatic aldehydes were converted to the respective β-hydroxynitro derivatives with good enantioselectivities, and in moderate yields. These catalytic conditions were found to be ineffective for simple aromatic aldehydes or those containing electron-releasing substituents.