The Reactivity of α‐Fluoroketones with PLP Dependent Enzymes: Transaminases as Hydrodefluorinases

A chemical method for the treatment of harmful halogenated compounds that has recently become of interest is the reductive dehalogenation of carbon‐halogen bonds. In the case of a fluorine atom, this process is called hydrodefluorination. While many transition metal‐based approaches now exist to reductively defluorinate aromatic fluoroarenes, the cleavage of C−F bonds in aliphatic compounds is not so well‐developed. Here we propose a biocatalytic approach exploiting a promiscuous activity exhibited by transaminases (TAs). Hence, a series of α‐fluoroketones have been defluorinated with excellent conversions using Chromobacterium violaceum and Arthrobacter sp. TAs under mild conditions and in aqueous medium, using a stoichiometric amount of an amine (e. g. 2‐propylamine) as reagent and formally releasing its oxidized form (e. g. acetone), with ammonia and hydrogen fluoride as by‐products. It is also demonstrated that this process can be performed in a regio‐ or stereoselective fashion. The hydrodefluorination of various α‐fluoroketones has been performed under mild reaction conditions and in aqueous medium taking advantage of the promiscuous activity shown by transaminases using a stoichiometric amount of, e. g. 2‐propylamine, releasing in this case acetone, ammonia and hydrogen fluoride as by‐products. The process could be done in a regio‐ or even in a stereoselective manner.