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Nanomole-scale assignment of configuration for primary amines using a kinetic resolution strategy
Shawn M Miller1, Renzo A Samame, Scott D Rychnovsky
1Department of Chemistry, 1102 Natural Sciences II, University of California-Irvine, Irvine, California 92697, United States.
Journal of the American Chemical Society
|December 6, 2012
Summary
Determining the stereochemistry of primary amines is now simpler. A new kinetic resolution method uses enantioselective acylating agents and mass spectrometry for accurate configuration assignment, even for small samples.
Area of Science:
- Organic Chemistry
- Analytical Chemistry
- Stereochemistry
Background:
- Assigning absolute configurations of chiral molecules like primary amines is crucial in chemistry.
- Existing methods for determining amine stereochemistry can be complex or require large sample amounts.
Purpose of the Study:
- To develop a straightforward and sensitive method for assigning the absolute configurations of primary amines.
- To utilize a kinetic resolution strategy with novel enantioselective acylating agents.
Main Methods:
- Employed Mioskowski's enantioselective 1-(R,R) and 2-(S,S) acylating agents for kinetic resolution of primary amines.
- Developed a simple mnemonic to aid in determining the assigned configuration.
- Utilized a pseudoenantiomeric pair of reagents (1-(R,R) and 2-(S,S)-d(3)) for assaying amines on a micromolar scale.
- Analyzed resulting acetamide products using Electrospray Ionization-Mass Spectrometry (ESI-MS).
Main Results:
- The ESI-MS analysis of acetamide products accurately reflected the selectivity factors determined through kinetic experiments.
- The method demonstrated high enantioselectivity in assigning configurations.
- The developed strategy successfully determined configurations for mixtures of amines.
- The method was validated for amine samples as small as 50 nanomoles.
Conclusions:
- A novel, efficient, and sensitive method for assigning primary amine absolute configurations has been established.
- The combination of kinetic resolution, a mnemonic, and ESI-MS provides a powerful tool for stereochemical analysis.
- This approach is applicable to complex mixtures and requires minimal sample quantities, advancing chiral amine analysis.
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