- Catalytic Promiscuity of Transaminases: Preparation of Enantioenriched β-Fluoroamines by Formal Tandem Hydrodefluorination/Deamination
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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 β-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 β-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.
- Cuetos, Aníbal,García-Ramos, Marina,Fischereder, Eva-Maria,Díaz-Rodríguez, Alba,Grogan, Gideon,Gotor, Vicente,Kroutil, Wolfgang,Lavandera, Iván
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supporting information
p. 3144 - 3147
(2016/03/12)
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- Enantioenriched 1-aryl-2-fluoroethylamines. Efficient lipase-catalysed resolution and limitations to the Mitsunobu inversion protocol
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Both enantiomers of eight 1-aryl-2-fluoroethylamines have been synthesised starting with 1-aryl-2-fluoroethanones. Kinetic resolution of the amines using lipase B from Candida antarctica with ethyl methoxyacetate as the acyl donor gave the (R)-amines in 96-99% ee and the (S)-methoxyacetamides in >99.5% ee. The resolution was robust with respect to variation in reaction temperature, acyl donor concentration, water activity and substrate structure. Nine other lipase preparations failed to catalyse the reaction or gave a low enantioselectivity. Secondly, a Mitsunobu inversion protocol starting with enantioenriched 1-aryl-2-fluoroethanols using phthalimide as nucleophile was employed in the synthesis of the (S)-1-aryl-2-fluoroethylamines. Both the inversion efficiency and yield depended on the aromatic substituents. For six of the substrates, clean inversion of the stereochemistry was observed. However, racemisation and low yields were the result when electron-donating substituents were present at the aromatic ring. When substituted with a cyano or a nitro group, an unexpected fluorine elimination occurred, limiting the yield for these transformations. The absolute configuration of the 1-aryl-2-fluoroethylamines was determined using circular dichroism.
- Thvedt, Thor Hkon Krane,Fuglseth, Erik,Sundby, Eirik,Hoff, Brd Helge
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experimental part
p. 6733 - 6743
(2010/09/30)
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