Biomimetic Reductive Amination of Fluoro Aldehydes and Ketones via [1,3]-Proton Shift Reaction.(1) Scope and Limitations.
A systematic study of azomethine-azomethine isomerizations of the N-benzylimines 2, derived from fluorinated aldehydes or ketones and benzylamine, has been made. The results reveal that, in sharp contrast to hydrocarbon analogs, fluorinated imines of 2 in triethylamine solution undergo isomerizations to give the corresponding N-benzylidene derivatives 5 (for 5/2 K > 32) in good isolated yields. The rates of the isomerizations 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 ketimine 2i,j. The presence of chlorine or bromine atoms in the alpha-position to the C=N double bond of the starting imine favors a dehydrohalogenation reaction, giving rise to unsaturated products 6-9. The azomethine-azomethine isomerization was studied and proven to proceed essentially (>98%) intramolecularly with isotope exchange experiments. High chemical 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.
Ono
Taizo
T
National Industrial Research Institute of Nagoya, Hirate-cho 1-1, Kita-ku, Nagoya City, Aichi Prefecture 462, Japan, and Institute of Bioorganic Chemistry and Petrochemistry, Ukrainian Academy of Sciences, Kiev 253160, Ukraine.
Kukhar
Valery P.
VP
Soloshonok
Vadim A.
VA