Document Type


Publication Date



MIDA boronates (N-methylimidodiacetic boronic acid esters) serve as an increasingly general platform for building-block-based small molecule construction, largely due to the dramatic and general rate differences with which they are hydrolysed under various basic conditions. Yet the mechanistic underpinnings of these rate differences have remained unclear, hindering efforts to address current limitations of this chemistry. Here we show that there are two distinct mechanisms for this hydrolysis: one is base-mediated and the other neutral. The former can proceed more than three orders of magnitude faster, and involves rate-limiting attack at a MIDA carbonyl carbon by hydroxide. The alternative ‘neutral’ hydrolysis does not require an exogenous acid/base and involves rate-limiting B-N bond cleavage by a small water cluster, (H2O)n. The two mechanisms can operate in parallel, and their relative rates are readily quantified by 18O incorporation. Whether hydrolysis is ‘fast’ or ‘slow’ is dictated by the pH, the water activity (aw), and mass-transfer rates between phases. These findings stand to rationally enable even more effective and widespread utilisation of MIDA boronates in synthesis.


This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Nature Chemistry, volume 8, in 2016 following peer review. The definitive publisher-authenticated version is available online at DOI: 10.1038/nchem.2571. It is also freely available through the Springer Nature ShareIt initiative here.


The authors



To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.