General Methods for Synthesis of N-Methyliminodiacetic Acid Boronates from Unstable ortho-Phenolboronic Acids

Abstract

A range of N-methyliminodiacetic acid (MIDA) boronates of commercially available but unstable ortho-phenolboronic acid derivatives can be readily prepared through simple condensation between the corresponding phenolboronic acids and MIDA in the presence of molecular sieves. The resulting MIDA boronates are bench-top stable and display a remarkable stability even in DMSO solution at high temperature (>120 degrees C) compared with their parent boronic acids. Moreover, the utility of the resulting MIDA boronate was successfully demonstrated in a cross-coupling reaction using the slow-release protocol to afford the cross-coupled product in much better yield compared with its parent boronic acid counterpart. In addition, an alternative, but more efficient, synthetic route for difficult-to-access ortho-phenol MIDA boronates has been developed through the MIDA boronate formation of methoxymethyl (MOM) protected ortho-phenolboronic acid, followed by deprotection of the MOM group with TMSCl under ambient conditions.