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Multistep synthesis of complex boronic acids from simple MIDA boronates
Eric P Gillis1, Martin D Burke
1Roger Adams Laboratory, Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Journal of the American Chemical Society
|October 8, 2008
Summary
Air-stable MIDA boronates overcome limitations in synthetic chemistry. These stable compounds enable multistep synthesis of complex boronic acid building blocks, facilitating advanced organic synthesis.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Medicinal Chemistry
Background:
- Boronic acids are crucial in organic synthesis but sensitive to many reagents.
- Their instability necessitates late-stage introduction, limiting synthetic strategies.
Purpose of the Study:
- To develop stable boronic acid surrogates for complex molecule synthesis.
- To enable multistep synthesis utilizing boronic acid building blocks.
Main Methods:
- Synthesis and characterization of N-methyliminodiacetic acid (MIDA) boronates.
- Compatibility studies with common synthetic reagents.
- X-ray crystallography and variable temperature NMR spectroscopy.
- Total synthesis of (+)-crocacin C using MIDA boronates.
Main Results:
- MIDA boronates exhibit exceptional stability to air and common reagents.
- Stability is attributed to kinetic inaccessibility of the boron p-orbital and nitrogen lone pair.
- Demonstrated utility in iterative cross-coupling reactions.
- Achieved a modular total synthesis of (+)-crocacin C.
Conclusions:
- MIDA boronates represent a significant advancement in handling and utilizing boronic acids.
- This methodology simplifies the synthesis of complex boronic acid derivatives.
- Enables efficient construction of intricate molecular architectures, including natural products.
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