A general solution for unstable boronic acids: slow-release cross-coupling from air-stable MIDA boronates

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Medicinal Chemistry

Background:

• Many valuable boronic acid derivatives, such as 2-heterocyclic, vinyl, and cyclopropyl types, exhibit inherent instability.
• This instability restricts their practical utility in laboratory settings, limiting benchtop storage and hindering efficient participation in cross-coupling reactions.

Purpose of the Study:

• To develop a general and robust method for overcoming the instability of various boronic acid derivatives.
• To transform unstable boronic acids into shelf-stable and readily usable building blocks for organic synthesis.

Main Methods:

• The study introduces a novel approach involving the in situ slow release of unstable boronic acids.
• This release is achieved from their corresponding N-methyliminodiacetic acid (MIDA) boronate precursors, which are air-stable.

Main Results:

• The developed method successfully stabilizes three classes of previously unstable boronic acids: 2-heterocyclic, vinyl, and cyclopropyl derivatives.
• These stabilized boronic acids, generated in situ from MIDA boronates, function as highly effective building blocks.
• They demonstrate efficient cross-coupling capabilities with a diverse array of aryl and heteroaryl chlorides.

Conclusions:

• The in situ slow-release strategy from MIDA boronates provides a general solution for handling unstable boronic acids.
• This approach significantly enhances the accessibility and utility of these important synthetic intermediates.
• The method broadens the scope of cross-coupling reactions involving challenging boronic acid substrates.