ABSTRACT
Transaminases have shown the ability to catalyze the amination of a series of aliphatic and (hetero)aromatic α,α-difluorinated ketones with high stereoselectivity, thus providing the corresponding ß,ß-difluoroamines in high isolated yields (55-82%) and excellent enantiomeric excess (>99%). It was also observed that these activated substrates could be quantitatively transformed by employing a small molar excess of the amine donor since this amination process was thermodynamically favored. Selected transformations could be scaled up to 500 mg, showing the robustness of this methodology.
Subject(s)
Amines/chemical synthesis , Hydrocarbons, Fluorinated/chemistry , Ketones/chemistry , Transaminases/chemistry , Amination , Arthrobacter/enzymology , Bacterial Proteins/chemistry , Biocatalysis , Chromobacterium/enzymology , Molecular Structure , StereoisomerismABSTRACT
Transaminases are valuable enzymes for industrial biocatalysis and enable the preparation of optically pure amines. For these transformations they require either an amine donor (amination of ketones) or an amine acceptor (deamination of racemic amines). Herein transaminases are shown to react with aromatic ß-fluoroamines, thus leading to simultaneous enantioselective dehalogenation and deamination to form the corresponding acetophenone derivatives in the absence of an amine acceptor. A series of racemic ß-fluoroamines was resolved in a kinetic resolution by tandem hydrodefluorination/deamination, thus giving the corresponding amines with up to greater than 99 % ee. This protocol is the first example of exploiting the catalytic promiscuity of transaminases as a tool for novel transformations.
