Arylboronic Acid Functionality makes Phase Switching Possible

 

In the thesis of Paul O’Brien working with Professor Organ at York University in Toronto, there is useful information for using molecules containing aryl boronic acids as intermediates that enable a phase switching purification.

 This thesis teaches that phenyl boronates can be extracted into a water solution containing 1.0M D- Sorbitol at pH 11-13 and then after making the pH acidic, the boronate functionalized substrate can be taken back into a water-immiscible organic solvent, thus achieving a solvent switch that can provide a rugged tool for rapid purification.

“Hall demonstrated that aryl boronic acids are stable to reaction conditions such as IBX oxidations (2-iodoxybenzoic acid), DIBAL-H reductions, esterification of alcohols, amidations, Wittig reactions, and Grignard additions [Mothana, S.; Grassot, J.; Hall, D. G. Angew. Chem. Int. Ed. 2010, 49, 2883-2887].This strongly suggests that arylboronic acids may be stable to a range of rather harsh reaction conditions without resorting to protecting groups. 

Arylboronic acid tagging strategies also show good atom economy in contrast with other tagging methods because the tag can be utilized in chemical transformations such as Suzuki cross-coupling, Rhodium cross-coupling (C-N and C-C), chemoselective oxidations, catalytic hydrogenations, selective aerobic oxidative coupling, transition-metal free cross-coupling, and protodeboronation to name just a few.

The use of arylboronic acid moieties as phase-switching handles adds synthetic utility while reducing synthetic steps such as protection protocols for subsequent column chromatography. Purification of most boronic acids is difficult since they are highly polar, like carboxylic acids, and adhere to polar chromatography material such as silica. The degree of lipophilicity of the boronic acid substituent influences chromatographic adhesion, where highly lipophilic substituents decrease retention on silica. Another method to decrease the polarity is boronic acid protection using 1,2-diol such as catechol or pinacol esters to mask the polar -B(OH)₂ functionality as a lipophilic ester.”

I have made what I think are editorial changes in what is almost, but not quite, a quote.