MIDA boronates are hydrolysed fast and slow by two different mechanisms

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Chemical Kinetics

Background:

• N-methylimidodiacetic acid (MIDA) boronates are versatile building blocks in organic synthesis.
• Their utility is linked to tunable hydrolysis rates under basic conditions.
• The mechanistic basis for these rate differences has been poorly understood.

Purpose of the Study:

• To elucidate the distinct mechanisms governing MIDA boronate hydrolysis.
• To understand the factors controlling the rates of these hydrolysis pathways.
• To provide a mechanistic framework for optimizing MIDA boronate chemistry.

Main Methods:

• Investigation of MIDA boronate hydrolysis under varying pH conditions.
• Kinetic analysis to differentiate reaction pathways.
• Use of isotopic labeling (¹⁸O incorporation) to quantify reaction rates and mechanisms.

Main Results:

• Identified two parallel hydrolysis mechanisms: base-mediated and neutral.
• Base-mediated hydrolysis is significantly faster (>1000x) via hydroxide attack at the carbonyl carbon.
• Neutral hydrolysis involves rate-limiting B-N bond cleavage by water clusters.
• Hydrolysis rates are dependent on pH, water activity, and mass transfer.

Conclusions:

• The dual hydrolysis mechanisms provide a clear explanation for the observed rate variations in MIDA boronate chemistry.
• Understanding these mechanisms allows for rational control over MIDA boronate reactivity.
• This knowledge will facilitate broader and more efficient applications of MIDA boronates in synthetic chemistry.