Slow-Release of Unstable Boronic Acids from MIDA Boronates
By: Aaron Thornton, ChemFiles Volume 11 Article 1
Aaron Thornton, Ph.D.
In addition to attenuated reactivity towards anhydrous cross-coupling conditions, MIDA boronates also possess the capacity for in situ slowrelease of boronic acids under aqueous basic conditions (Scheme 1). Harnessing this phenomenon, boronic acids that are notoriously unstable can be eff ectively utilized in cross-coupling when employed as MIDA boronates. While aqueous solutions of NaOH promote the fast hydrolysis of MIDA boronates to their corresponding boronic acids, the use of aqueous K3PO4 allows for the slow-release of relatively unstable boronic acids, preventing decomposition of the organometallic species and improving overall yields for many Suzuki-Miyaura reactions.
Slow Release of Unstable Boronic Acids
Scheme 1: Slow-release of unstable boronic acids from MIDA boronates.
Burke and coworkers examined this slow-release concept by comparing various freshly prepared boronic acids with their corresponding MIDA boronates. The study revealed that many boronic acids decompose signifi cantly via various pathways, including protodeborylation, oxidation, and polymerization, after just 15 days of benchtop storage under air. On the other hand, the corresponding MIDA boronates were remarkably stable, with >95% of each MIDA remaining after ≥60 days of benchtop storage under air. In addition to complications related to storage, the overall efficiency of cross-coupling for these reagents is also impacted by the nature of the boron unit. For example, while isolated yields are generally low to moderate even when freshly-prepared boronic acids are employed in Suzuki-Miyaura cross-couplings, employing the corresponding MIDA boronate results in excellent yields of the desired cross-coupled products (Table 1).
Table 1: Stability and slow-release cross-coupling studies of MIDA boronates vs. boronic acids.