Background: In the field of asymmetric aminocatalysis, chiral catalysts
derived from azoles (five-membered heterocycles containing exclusively N atoms)
play an important role. Surprisingly, all the catalysts used for enamine and/or iminium
ion activation derive from pyrrole or imidazole. We decided to test if other reduced
azole derivatives could be used as organocatalysts and particularly in aminocatalysis
via iminium ion activation. The azole derivatives that came naturally to
mind are the 3,5-disubstituted 2-pyrazolines (also called 4,5-dihydro-1H-pyrazoles).
Methods: We synthesized racemic 3,5-diphenyl-2-pyrazoline, separated both enantiomers
by chiral-HPLC on a Lux-Cellulose-4 column (heptane/ethanol 70:30 as mobile
phase), determined the absolute configuration of their hydrochloride salts (pyrazolinium)
by the combined use of experimental rotatory power and B3LYP/6-311++G(d,p) theoretical
calculations and use one the enantiomers, the R, as the catalyst.
Results: We have demonstrated that the enantiopure (R)-3,5-diphenyl-2-pyrazoline is able to catalyze
the Michael addition of 1-(4-nitrophenyl)propan-2-one to cinnamaldehyde and crotonaldehyde via iminium
Conclusion: This is the first example of activation of both types of enals, aliphatic and aromatic, via
pyrazolinium salts and opens new possibilities to the design of other type of chiral organocatalysts than
the traditional pyrrole and imidazole derivatives.