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A Protocol for Safe Lithiation Reactions Using Organolithium Reagents
Published on: November 12, 2016
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The Development of Stereoselective Substrate and Reagent-Controlled Lithiation-Borylation Chemistry
Yannick Linne1, Maike Birkner1, Daniel Lücke1
1Institute of Organic Chemistry, Gottfried Wilhelm Leibniz Universität Hannover, Schneiderberg 1B, Hannover 30167, Germany.
The Journal of Organic Chemistry
|October 17, 2025
Summary
Chiral polyketide fragments enable stereoselective Hoppe-Matteson-Aggarwal rearrangement without sparteine. This method offers high yields and diastereoselectivities for synthesizing allylic alcohols, crucial in natural product synthesis.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Natural Product Synthesis
Background:
- Allylic alcohols are key structural units in polyketide natural products.
- Developing stereoselective methods for their synthesis is a significant challenge in organic chemistry.
Purpose of the Study:
- To develop a novel, highly stereoselective method for synthesizing allylic alcohols.
- To investigate the use of chiral polyketide fragments in the Hoppe-Matteson-Aggarwal rearrangement.
Main Methods:
- Utilizing chiral polyketide fragments to direct the Hoppe-Matteson-Aggarwal rearrangement.
- Investigating various stereodynads and stereotriads with different protecting and directing groups.
- Employing DFT-based conformational analysis and a Felkin-like model for stereochemical explanation.
Main Results:
- The Hoppe-Matteson-Aggarwal rearrangement was successfully performed without sparteine, achieving high yields and diastereoselectivities.
- Strong inherent substrate induction was observed, attributed to steric and/or electronic effects.
- A predictive model was developed for substrate- and reagent-controlled lithiation-borylation chemistry.
Conclusions:
- The developed protocol provides a valuable alternative for stereoselective allylic alcohol synthesis.
- Understanding substrate induction mechanisms aids in designing future synthetic strategies.
- The findings facilitate the construction of complex polyketide natural products.
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