EaStCHEM, School of Chemistry, University of Edinburgh, Edinburgh, EH9 3FJ, UK.
Department of Chemistry, Oregon State University, Corvallis, Oregon 97331, USA.
Nat Chem. 2016 Nov;8(11):1067-1075. doi: 10.1038/nchem.2571. Epub 2016 Jul 25.
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, (HO). The two mechanisms can operate in parallel, and their relative rates are readily quantified by O 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.
MIDA 硼酸酯（N-甲基亚氨基二乙酸硼酸酯）作为一种基于构建块的小分子构建的通用平台，越来越受到关注，这主要是因为它们在各种碱性条件下的水解速率差异非常显著且具有普遍性。然而，这些速率差异的机制仍然不清楚，这阻碍了对该化学的当前限制的解决。在这里，我们表明这种水解有两种不同的机制：一种是碱介导的，另一种是中性的。前者的速度可以比后者快三个数量级以上，涉及到一个由氢氧根离子在 MIDA 羰基碳上的限速进攻。另一种替代的“中性”水解不需要外部酸或碱，并且涉及到由小的水分子簇（HO）限速的 B-N 键断裂。这两种机制可以并行运行，它们的相对速率可以通过 O 掺入来轻易地定量。水解是“快”还是“慢”取决于 pH 值、水活度以及相之间的质量传递速率。这些发现有望以合理的方式，更有效地广泛利用 MIDA 硼酸酯进行合成。
