Synthesis of imminopyridine ligands and their application to enantioselective copper catalysed Henry reaction

The asymmetric nucleophilic addition to prochiral ketones or aldehydes is an excellent strategy for the formation of quaternary oxygenated chiral centres. The Henry or nitroaldol reaction was discovered in 1895 and it is now widely used in organic synthesis as it leads to ?-nitro alcohols that can be easily converted into a variety of intermediates for high values chemical compounds [1]. The first example of an enantioselective copper-catalyzed Henry reaction was reported by Jørgensen and co-workers in 2001, proving the ability of bis-oxazoline ligands in this process [2]. Since then, many types of chiral ligands have been developed and tested in copper catalyzed Henry reaction [3]. Among them, chiral N,N-ligands have been synthesized and their efficiency established in particular regarding iminopyridine ligands [3]. Since our continuous effort in the synthesis and characterization of chiral nitrogen based ligands [4] and their application to enantioselective catalysis, we report on the synthesis of a series of chiral pyridine-based imines (Scheme 1) and our preliminary results of their use in the asymmetric copper catalyzed addition of nitromethane to o methoxybenzaldehyde as a model substrate (Scheme 2).