Effect of the enamine pyramidalization direction on the reactivity of secondary amine organocatalysts
Tobias Schnitzer1, Jasper S Möhler1, Helma Wennemers1
1Laboratory of Organic Chemistry, ETH Zürich Vladimir-Prelog-Weg 3 8093 Zürich Switzerland Helma.Wennemers@org.chem.ethz.ch.
Abstract:
Chiral secondary amines are valuable catalysts for reactions that proceed through an enamine intermediate. Here, we explored the importance of the pyramidalization direction of the enamine-N on the reactivity of chiral enamines with a combination of computational, NMR spectroscopic, and kinetic experiments. Studies with peptidic catalysts that bear cyclic amines with different ring sizes revealed that endo-pyramidalized enamines are significantly more reactive compared to exo-pyramidalized analogs. The results show that the pyramidalization direction can have a greater effect than n→π* orbital overlap on the reactivity of chiral enamines. The data enabled the development of a catalyst with higher reactivity compared to the parent catalyst.
Related Concept Videos
Aldehydes and Ketones with Amines: Enamine Formation Mechanism
Aldehydes and Ketones with Amines: Imine and Enamine Formation Overview
Preparation of Amines: Reductive Amination of Aldehydes and Ketones
ortho–para-Directing Activators: –CH3, –OH, –⁠NH2, –OCH3
Preparation of 1° Amines: Azide Synthesis
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...
Aldehydes and Ketones with Amines: Imine Formation Mechanism
Imines are formed under mildly acidic conditions. A pH of 4.5 is ideal for the reaction.
If the pH is low or the solution is too acidic, the reaction slows down in the...

![[DPEPhosbcpCu]PF6: A General and Broadly Applicable Copper-Based Photoredox Catalyst](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F59739.jpg&w=3840&q=50)
