@article{5de20b4a850c4fb38101445b2ac6ff62,
title = "MIDA boronates are hydrolysed fast and slow by two different mechanisms",
abstract = "MIDA boronates (N-methylimidodiacetic boronic acid esters) serve as an increasingly general platform for small-molecule construction based on building blocks, largely because of 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, which has hindered efforts to address the 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 than the latter, and involves a rate-limiting attack by a hydroxide at a MIDA carbonyl carbon. The alternative 'neutral' hydrolysis does not require an exogenous acid or 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 and the mass-transfer rates between phases. These findings stand to enable, in a rational way, an even more effective and widespread utilization of MIDA boronates in synthesis.",
author = "Gonzalez, {Jorge A.} and Ogba, {O. Maduka} and Morehouse, {Gregory F.} and Nicholas Rosson and Houk, {Kendall N.} and Leach, {Andrew G.} and Cheong, {Paul H.Y.} and Burke, {Martin D.} and Lloyd-Jones, {Guy C.}",
note = "Funding Information: G.C.L.-J. is a European Research Council (ERC) Advanced Investigator. The research leading to these results has received funding from the ERC under the European Union's Seventh Framework Programme (FP7/2007-2013)/ERC grant agreement No. 340163, and the US National Institutes of Health. G.C.L.-J. and J.A.G. thank CONACYT and The University of Edinburgh for generous support. M.D.B. acknowledges financial support from the US National Institutes of Health (GM118185). P.H.-Y.C. is the Bert and Emelyn Christensen Professor of Oregon State University and acknowledges financial support from the Stone family and the US National Science Foundation (NSF, CHE-1352663). K.N.H. is the Saul Winstein Chair in Organic Chemistry at the University of California Los Angeles and acknowledges financial support from the US NSF (CHE-1059084). O.M.O. acknowledges Tartar research support. O.M.O. and P.H.-Y.C. also acknowledge computing infrastructure in part provided by the NSF Phase-2 CCI, Center for Sustainable Materials Chemistry (NSF CHE-1102637). Publisher Copyright: {\textcopyright} 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.",
year = "2016",
month = nov,
day = "1",
doi = "10.1038/nchem.2571",
language = "English (US)",
volume = "8",
pages = "1067--1075",
journal = "Nature Chemistry",
issn = "1755-4330",
publisher = "Nature Publishing Group",
number = "11",
}