Synthesis of chiral salalen ligands and their in‐situ generated Cu‐complexes for asymmetric Henry reaction

Abstract

Chiral salalen ligands derived from (S)‐proline and derivatives of salicyaldehydes were synthesized, and their in‐situ generated Cu (II) complexes were evaluated in the asymmetric Henry reaction. Salalen ligand of different substituents on the phenyl moiety showed remarkable effect on the enantioselectivity of nitro‐aldol product of 4‐nitrobenzaldehyde and nitromethane. Cu (II) complex generated in situ with (S)‐2‐(tert‐butyl)‐6‐((2‐(((2‐hydroxy‐3‐methylbenzylidene)amino)methyl)pyrrolidin‐1‐yl)methyl) phenol (10 mol%) and Cu (OAc)2.H2O (10 mol%), found to be better catalyst for nitro‐aldol reaction between 4‐nitrobenzaldehyde and nitromethane, gave corresponding product in 85% yield and 88% enantiomeric excess (ee) in isopropanol at 35°C after 40 hours. The catalyst also used for the Henry reaction with different substituted benzaldehydes and corresponding products were obtained in 22% to 99% yields with 66% to 92% ee. Henry reaction of 4‐nitrobenzaldehyde and prochiral nitroethane gave anti‐selective product (dr = 79/21; anti/syn) in a 91% yield with 80% ee.