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Evans Enolates: Solution Structures of Lithiated Oxazolidinone-Derived Enolates
Evan H Tallmadge1, David B Collum1
1Baker Laboratory, Department of Chemistry and Chemical Biology, Cornell University , Ithaca, New York 14853-1301, United States.
Journal of the American Chemical Society
|October 6, 2015
Summary
Lithium enolates form complex aggregates like dimers and tetramers in solution. Their structures depend on the specific oxazolidinone auxiliary and solvent conditions.
Area of Science:
- Organic Chemistry
- Spectroscopy
- Computational Chemistry
Background:
- Oxazolidinone-based enolates are crucial intermediates in asymmetric synthesis.
- Understanding their aggregation state in solution is key to controlling reactivity.
- Previous studies suggested various aggregation behaviors, but detailed structural insights were limited.
Purpose of the Study:
- To elucidate the aggregation states and structures of oxazolidinone-based lithium enolates in tetrahydrofuran (THF) solution.
- To investigate the influence of auxiliary structure, enolate substitution, and solvent composition on aggregation.
- To provide a comprehensive understanding of these key synthetic intermediates.
Main Methods:
- Nuclear Magnetic Resonance (NMR) spectroscopy, specifically Lithium-6 (6Li) and Carbon-13 (13C) NMR.
- Computational studies, including density functional theory (DFT) calculations.
- Variable concentration studies in THF and THF/toluene mixtures.
Main Results:
- A mixture of dimers, tetramers, and oligomers (potentially ladders) was observed.
- Aggregation state distribution was sensitive to the oxazolidinone auxiliary structure and enolate substituents.
- Tetramers in unsolvated conditions exhibited a D(2d)-symmetric core.
- Dimers were identified as trisolvates with multiple isomeric forms, confirmed by both experimental and computational data.
Conclusions:
- The aggregation behavior of lithium enolates is complex and highly dependent on molecular and environmental factors.
- Detailed structural characterization of these aggregates is achievable through combined spectroscopic and computational approaches.
- This work provides critical insights into the solution-state structures of Evans enolates, relevant for stereoselective synthesis.
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