Background:
While proline can catalyze the asymmetric direct aldol reactions, its catalytic
activity and catalyst turnover are both low. To improve the catalytic efficiency, many prolinebased
organocatalysts have been developed. In this regard, prolinamide-based bifunctional catalysts
have been demonstrated by us and others to be highly efficient catalysts for the direct aldol reactions.
Results:
Using the β-acetamido- and β-tosylamidoprolinamide catalysts, the highly enantio- and diastereoselective
direct aldol reactions between enolizable ketones and aldehydes were achieved (up to
>99% ee, 98:2 dr). A low catalyst loading of only 2-5 mol % of the β-tosylamidoprolinamide catalyst
was needed to obtain the desired aldol products in good to high yields and high stereoselectivities.
Methods:
By carefully adjusting the hydrogen bonding ability of the remote β-amide hydrogen of the
1,2-diamine-based prolinamide bifunctional catalysts, the catalytic activity and the asymmetric induction
of these catalysts were significantly improved for the direct aldol reaction between aldehydes
and enolizable ketones.
Conclusion:
Some highly efficient 1,2-diamine-based bifunctional prolinamide catalysts have been
developed through probing the remote β-amide hydrogen for its hydrogen bonding capability. These
catalysts are easy to synthesize and high enantioselectivities may be achieved at very low catalyst
loadings.
Synergistic Effects of Conjugation and Polarization on Dual Amide Hydrogen-bonding in CCl4: Theory and Experiment
