Bijvoet in solution reveals unexpected stereoselectivity in a Michael addition

Area of Science:

• Organic Chemistry
• Spectroscopy
• Computational Chemistry

Background:

• Establishing absolute configuration is crucial in stereocontrolled organic synthesis.
• Crystallization-independent methods are needed for non-crystallizable compounds.
• Anomalous X-ray diffraction is limited to crystallizable molecules.

Purpose of the Study:

• To present a novel methodology for determining absolute configuration without crystallization.
• To elucidate the absolute stereochemistry of a Michael addition product.
• To overcome challenges in determining solution-state stereochemistry for flexible molecules.

Main Methods:

• Utilizing residual dipolar coupling enhanced NMR spectroscopy to generate structural ensembles.
• Employing Density Functional Theory (DFT) calculations to predict optical rotation dispersion (ORD) spectra.
• Comparing predicted ORD spectra with experimental results for absolute configuration assignment.

Main Results:

• A new fundamental methodology for resolving absolute configuration in solution has been developed.
• The method successfully determined the absolute stereochemistry of a novel Michael addition product.
• The combined NMR-DFT approach proved effective for flexible molecules.

Conclusions:

• The presented methodology offers a powerful alternative to crystallization for determining absolute configuration.
• This approach enhances the analysis of stereochemistry in flexible organic molecules.
• The study highlights the synergy between advanced NMR techniques and computational chemistry.