A simple generic method for analyzing water sensitive pinacol boronate compounds by hydrophilic interaction liquid chromatography

Abstract

Pinacol boronates are widely used in the pharmaceutical and biomedical industries as primary building blocks for many chemical reactions, such as Suzuki coupling. However, pinacol boronate esters are often susceptible to hydrolysis and degrade into corresponding boronic acids. This causes a challenge for analyzing these boronates by reversed-phase HPLC (RPLC), where hydrolysis occurs on the column. On the other hand, boronic acids are polar compounds and difficult to be retained in RPLC. Presently, there is a lack of practical and versatile analytical methods that can accurately and simultaneously analyze a wide range of boronate esters and boronic acids. In this work, a simple generic method was developed using hydrophilic interaction liquid chromatography (HILIC) separation to overcome these challenges. More than 40 pinacol boronate compounds in a broad range of diverse structures were screened using ten different HILIC stationary phases. Among all the stationary phases studied, ZIC-cHILIC column demonstrated excellent selectivity and retention of pinacol boronate esters and boronic acids for all of the compounds studied. The high percentage of organic solvent mobile phase in HILIC mode effectively prevents the on-column hydrolysis and provides excellent solubility for boronate ester samples. The compatibility of HILIC mobile phase allows the peaks to be identified directly by mass spectrometry.

Keywords

• Pinacol boronate
• On-column degradation
• HILIC
• Generic method