Abstract
This account shows our efforts towards the development of new N ,N -ligands
and their application in the asymmetric Henry reaction. Iminopyridine
ligands were prepared by the condensation of chiral monoterpene
ketones and pyridinylalkylamines. The complexes of these ligands
with copper(II) ions catalyzed the enantioselective addition
of nitromethane to aldehydes with generally high yields and moderate
enantioselectivities. The same reaction with other nitroalkanes
gave racemic products. Stereoselective reduction of the imino group
allowed us to obtain new aminopyridine ligands. The new ligands
were shown to be more efficient, and they catalyzed the addition
of nitromethane and also larger nitroalkanes to aldehydes to give
the corresponding products in generally very high yields and excellent
enantiomeric excesses. We have used this aminopyridine catalytic
system in the first catalytic enantioselective Henry reactions with
bromo(nitro)methane and methyl 4-nitrobutanoate. The reaction involving
the latter substrate gave multifunctional chiral building blocks
that were transformed into γ-lactams and δ-lactones.
The application of the reaction to the synthesis of known amino(aryl)ethanol
pharmaceuticals is also reported. Iminopyridine ligands,
however, were more efficient in the addition of nitromethane to α-keto
esters.
1 Introduction
1.1 Enantioselective Copper(II)-Catalyzed Henry Reaction
2 Enantioselective Henry Reaction with Aldehydes Catalyzed by
Copper(II)-Iminopyridine Complexes
2.1 Design and Synthesis of Iminopyridine Ligands
2.2 Enantioselective Addition of Nitromethane to Aldehydes
2.3 Stereochemical Models
3 Enantioselective Henry Reaction with Aldehydes Catalyzed by
Copper(II)-Aminopyridine Complexes
3.1 Design and Synthesis of Aminopyridine Ligands
3.2 Enantioselective Addition of Nitroalkanes to Aldehydes
3.3 Enantioselective Addition of Bromo(nitro)methane to Aldehydes
3.4 Enantioselective Addition of Methyl 4-nitrobutanoate to Aldehydes
3.5 Synthesis of Chiral Amino(aryl)ethanol Derivatives
4 Enantioselective Henry Reaction with α-Keto Esters
5 Conclusion
Key words
asymmetric catalysis - nucleophilic additions - nitro alcohols -
C
1 -symmetry -
N ,N -ligands
