BIOMIMETIC REDUCTIVE AMINATION OF FLUORO ALDEHYDES AND KETONES VIA [1,3]-PROTON SHIFT REACTION - SCOPE AND LIMITATIONS

A systematic study of azomethine-azomethine isomerizations of the N-be nzylimines 2, derived from fluorinated aldehydes or ketones and benzyl amine, has been made. The results reveal that, in sharp contrast to hy drocarbon analogs, fluorinated imines of 2 in triethylamine solution u ndergo isomerizations to give the corresponding N-benzylidene derivati ves 5 (for 5/2 K > 32) in good isolated yields. The rates of the isome rizations depend on the starting imine structures and increase in the following order: aryl perfluoroalkyl ketimine 2m, per(poly)fluoroalkyl aldimine 2a,d-g, perfluoroaryl aldimine 2h, alkyl perfluoroalkyl keti mine 2ij. The presence of chlorine or bromine atoms in the alpha-posit ion to the C=N double bond of the starting imine favors a dehydrohalog enation reaction, giving rise to unsaturated products 6-9. The azometh ine-azomethine isomerization was studied and proven to proceed essenti ally (>98%) intramolecularly with isotope exchange experiments. High c hemical yields, the simplicity of the experimental procedure, and the low cost of all reagents employed make this biomimetic transamination of fluorocarbonyl compounds a practical method for preparing fluorine- containing amines of biological interest.