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Synthesis of a Borylated Ibuprofen Derivative Through Suzuki Cross-Coupling and Alkene Boracarboxylation Reactions
Published on: November 30, 2022
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Pd(II)-Catalyzed Enantioselective C(sp3)-H Borylation
Jian He1, Qian Shao1, Qingfeng Wu1
1Department of Chemistry, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
Journal of the American Chemical Society
|February 18, 2017
Summary
Chiral ligands enable the first enantioselective borylation of C(sp3)-H bonds in amides. This breakthrough provides access to valuable chiral building blocks for synthesizing complex carboxylic acid derivatives.
Area of Science:
- Organic Chemistry
- Catalysis
- Asymmetric Synthesis
Background:
- C-H bond functionalization is a key strategy in organic synthesis.
- Enantioselective synthesis of chiral carboxylic acid derivatives remains challenging.
- Palladium catalysis offers powerful tools for C-H activation.
Purpose of the Study:
- To develop the first Pd(II)-catalyzed enantioselective borylation of C(sp3)-H bonds.
- To utilize chiral acetyl-protected aminomethyl oxazoline ligands for asymmetric induction.
- To demonstrate the utility of the generated chiral β-borylated amides.
Main Methods:
- Palladium(II) catalysis
- Use of chiral acetyl-protected aminomethyl oxazoline ligands
- Substrate scope exploration with carbocyclic amides (α-tertiary and α-quaternary centers)
Main Results:
- Successful enantioselective borylation of C(sp3)-H bonds in carbocyclic amides.
- High compatibility with sterically hindered α-tertiary and α-quaternary carbon centers.
- Formation of chiral β-borylated amides as versatile intermediates.
Conclusions:
- This study presents a novel method for asymmetric C-H borylation.
- The developed methodology provides efficient access to chiral β-borylated amides.
- These synthons are valuable for preparing diverse chiral carboxylic acid derivatives.
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