Enantioselective organocatalytic allylic amination
Thomas B Poulsen1, Carlos Alemparte, Karl Anker Jørgensen
1The Danish National Research Foundation: Center for Catalysis, Department of Chemistry, Aarhus University, DK-8000 Aarhus C, Denmark.
Journal of the American Chemical Society
|August 18, 2005
Summary
A novel organocatalysis method enables highly enantioselective allylic amination. This efficient strategy creates valuable chiral building blocks for synthesizing bioactive compounds like quinacrine and chloroquine.
Area of Science:
- Organic Chemistry
- Catalysis
- Medicinal Chemistry
Background:
- Allylic amination is crucial for synthesizing nitrogen-containing compounds.
- Developing enantioselective methods is essential for accessing chiral molecules.
- Organocatalysis offers a metal-free alternative for asymmetric synthesis.
Purpose of the Study:
- To develop a new organocatalytic strategy for enantioselective allylic amination.
- To demonstrate the direct functionalization of alkylidene cyanoacetates and malononitriles.
- To showcase the utility of the resulting chiral products in synthesizing bioactive compounds.
Main Methods:
- Utilized a commercially available organocatalyst.
- Employed alkylidene cyanoacetates and malononitriles as substrates.
- Reacted substrates with azodicarboxylates under catalytic conditions.
Main Results:
- Achieved direct, highly enantioselective allylic electrophilic functionalization.
- The reaction exhibited a broad scope, high yields, and enantioselectivities up to 99%.
- Demonstrated synthetic utility through diastereoselective Diels-Alder reactions, reductions, and formation of chiral building blocks.
Conclusions:
- The developed organocatalytic strategy provides an efficient route to enantiomerically enriched products.
- The chiral building blocks are valuable intermediates for synthesizing pharmaceuticals like quinacrine and chloroquine analogues.
- This method expands the toolkit for asymmetric synthesis in organic chemistry.
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