Synthesis of 1,2-Diamine Bifunctional Catalysts for the Direct Aldol Reaction Through Probing the Remote Amide Hydrogen

Author(s): Rajasekhar Dodda, Sampak Samanta, Matthew Su, John C.-G. Zhao*.

Journal Name: Current Organocatalysis

Volume 6 , Issue 2 , 2019

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Abstract:

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 proline-based 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.

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.

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 β-tosylamidoprolinamide catalyst was needed to obtain the desired aldol products in good to high yields and high stereoselectivities.

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.

Keywords: Aldol, amide, asymmetric, bifunctional, catalysis, hydrogen bonding, proline.

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Article Details

VOLUME: 6
ISSUE: 2
Year: 2019
Page: [171 - 176]
Pages: 6
DOI: 10.2174/2213337206666190301155247