In linking to Neal Anderson yesterday, I see that he has a new post up and it's a bit of a doozy:
Arylboronic acids, but not the corresponding deboronated arenes, recently have been found to be weakly mutagenic in microbial assays . Hence arylboronic acids may be considered potentially genotoxic impurities, and controlling the levels of residual arylboronic acids in APIs could become a regulatory requirement. The issues should be decided by toxicology studies for the specific arylboronic acids in question.Wait, what? Arylboronic acids might be genotoxic? Uh-oh. He then launches into a long discussion of how to cause protodeboronation of boronic acids to remove them from your API: (I think if you printed out his blogpost and sent it to Boron Molecular in North Carolina, either the envelope or the building would self-destruct.)
The Snieckus group found that deboronation occurred readily when pinacol was added to 4-pyridylboronic acid . Percec and co-workers found that deboronation of neopentylglycol boronates, especially an ortho-substituted arylboronic acid ester, was catalyzed by nickel species . Kuivila and co-workers found that CuCl2 catalyzed the deboronation of 2,6-dimethoxybenzeneboronic acid and other arylboronic acids, with formation of the corresponding aryl chlorides . Unfortunately, adding reagents to a reaction mixture increases the burdens of analysis and impurity removal, but additives such as these may accelerate deboronation in difficult cases. Simply extending the reaction conditions, which are generally basic for efficient Suzuki coupling, or heating with some amount of aqueous hydroxide are probably the preferred treatments to decompose an arylboronic acid. By knowing the kinetics of the decomposition of the arylboronic acid it may be possible to show by QbD that analyses for the residual arylboronic acid in an API are not necessary.Read the whole thing.