(Salen)Titanium-Catalyzed Asymmetric Hydrogen Atom Transfer for Epoxides Reduction
Zhongyun Xu1, Jian Shen1, Longfei Li1
1School of Chemistry and Chemical Engineering, Shandong University, Jinan, 250100, China.
Angewandte Chemie (International Ed. in English)
|October 21, 2022
Summary
This study introduces a novel catalytic method for asymmetric hydrogen atom transfer, creating chiral centers efficiently. The reaction converts readily available esters and amides into valuable aldol adducts with high selectivity.
Area of Science:
- Organic Chemistry
- Asymmetric Synthesis
- Catalysis
Background:
- Chiral tertiary carbon centers are crucial building blocks in pharmaceuticals and natural products.
- Asymmetric hydrogen atom transfer (HAT) is a direct route to these centers but remains challenging.
- Existing methods often lack efficiency or broad applicability.
Purpose of the Study:
- To develop the first catalytic coordination-induced asymmetric HAT reaction.
- To enable enantioselective synthesis of valuable chiral compounds from simple precursors.
- To overcome the long-standing challenge in asymmetric HAT.
Main Methods:
- Utilizing a sequential mechanism involving (salen)Ti^III-initiated radical generation.
- Employing a (salen)Ti^IV-controlled enantioselective HAT process.
- Applying the method to glycidic esters, thioesters, and amides.
Main Results:
- Demonstrated the first example of catalytic coordination-induced asymmetric HAT.
- Achieved enantioconvergent synthesis of formal formaldehyde aldol adducts.
- Showcased broad substrate scope with high regio- and enantioselectivities.
Conclusions:
- The developed method provides a powerful new tool for accessing chiral tertiary carbons.
- This work significantly advances the field of asymmetric hydrogen atom transfer.
- The reaction offers a practical and efficient route to valuable synthetic intermediates.
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