Asymmetric Pd/Organoboron-Catalyzed Site-Selective Carbohydrate Functionalization with Alkoxyallenes Involving
Hao Guo1,2, Jan-Lukas Kirchhoff3, Carsten Strohmann3
1Abteilung Chemische Biologie, Max Planck Institut für Molekulare Physiologie, Otto-Hahn-Straße 11, 44227, Dortmund, Germany.
Angewandte Chemie (International Ed. in English)
|March 26, 2024
Summary
This study showcases a chiral palladium/organoboron system for precise carbohydrate modification. Noncovalent interactions were unexpectedly key to controlling stereoselectivity in this catalytic approach.
Area of Science:
- Organic Chemistry
- Catalysis
- Carbohydrate Chemistry
Background:
- Stereoselective synthesis of complex carbohydrates is crucial for developing biologically relevant molecules.
- Controlling multiple selectivity issues (site, regio, enantio, diastereoselectivity) simultaneously remains a significant challenge.
- Noncovalent interactions (NCIs) are increasingly recognized for their role in directing stereochemical outcomes in organic synthesis.
Purpose of the Study:
- To develop a robust catalytic system for highly selective functionalization of carbohydrate polyols.
- To investigate the mechanistic role of noncovalent interactions in achieving complex stereocontrol.
- To demonstrate the utility of a synergistic chiral palladium/organoboron system.
Main Methods:
- Utilized a chiral palladium/organoboron catalytic system with prochiral alkoxyallenes as electrophiles.
- Performed mechanistic experiments to probe reaction pathways and intermediate interactions.
- Employed Density Functional Theory (DFT) modeling to analyze the reaction mechanism and stereoselectivity determinants.
Main Results:
- Achieved high levels of site-, regio-, enantio-, and diastereoselectivity in the functionalization of diverse carbohydrate polyols.
- Uncovered the critical involvement of noncovalent interactions (hydrogen bonding, CH-π interactions) in controlling stereoselectivity.
- Demonstrated the synergistic effect between the palladium catalyst and the organoboron moiety.
Conclusions:
- The chiral Pd/organoboron system effectively addresses multiple stereoselectivity challenges in carbohydrate synthesis.
- Noncovalent interactions play a pivotal, previously underestimated role in transition metal-catalyzed stereoselective reactions.
- This work highlights a new strategy for harnessing NCIs to enhance stereocontrol in carbohydrate functionalization.
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