Applications of Hexyleneglycol Arylboronic Esters

Conditions Pd(OAc)2 (1 mol.%), CS2CO3 (2 equiv.), toluene/MeOH (4 1), 60 °C the indicated durations are for complete reactions.  

The synthesis of lapatinib involves a Suzuki-Miyaura coupling of a (5-formylfuran-2-yl)boronic derivative and an aryl iodide and was studied in detail by several teams. In a recent patent,researchers from Zentiva noticed that in their own attempts to use commercial boronic acid, the excess of this reagent required for optimal conversions and purity was dependent on the source (a common issue with boronic acids, which are often contaminated with anhydrides and borinic acid). Thus, they turned to cyclic boronic esters as a more reliable intermediate, allowing correct control of the amount of boron reagent. Transposition of a process originally developed for the coupling of (5-formylfuran-2-yl)boronic acid was successful. The authors compared 

The above examples show that the dioxaborinanes ArBhg and ArBnpg react in higher yields in Suzuki-Miyaura couplings than their Bpin counterparts, and hint that the use of pinacol as the protecting diol for boronic esters should not be so systematic in the context of Suzuki-Miyaura reactions.  

The present survey of the reactivity of six-membered, sterically hindered, boronic esters aimed to demonstrate that there are, beyond pinacolboronic esters, other reagents that often exhibit a better stability-reactivity ratio. The comingyears should see a steady shift from ubiquitous pinaeol to a reasoned choice of the best boronic ester for a particular application. 

Ishiyama and N. Miyaura, in Boronic Acids, ed. D. G. Hall, Wiley-VCH Verlag GmbH, 2011, p. 135. 

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