α-Ferrocenylalkylation of some biologically active compounds

Abstract

a-Ferrocenylalkylation reactions [1] are used to prepare various ferrocene derivatives exhibiting a wide spectrum of biological activity [2, 3]. With the goal of further search for more efficient compounds of this series, in the present work we effected for the first time a-ferrocenylalkylation of some biologically active compounds [4], such as Cyclophosphan, 5-fluorouracil (as sodium salt), and glycine and phenylalanine ethyl esters, by the action of ferrocenylmethanol (I) in the two-phase system CH2Cl23 48% aqueous HBF4 at room temperature under vigorous stirring. It is known [5] that under these conditions a-ferrocenylcarbocation II is readily generated from alcohol I. Cation II reacts with the above nucleophilic substrates at their most electron-rich centers. As a result, we obtained in high yields ferrocene-containing compounds III3VI (Scheme 1) whose structure was confirmed by the data of elemental analysis, IR and H NMR spectroscopy, and mass spectrometry and by chemical transformations. The IR spectra of compounds III3VI contain absorption bands typical of vibrations of the ferrocenyl fragment [6] and other functional groups (PIO, CIO, NAH). Their H NMR spectra were also consistent with the assumed structures. Compound VI showed in the H NMR spectrum a double set of signals due to the presence of two isomers (N and and N) which we failed to separate by column chromatography on Al2O3 (compound VI turned out to be unstable). According to the H signal intensities, the ratio of the Nand N-isomers is 65 : 35. The mass spectra of III3VI contained low-intense (538%) molecular ion peaks; the most abundant ions were [FcCH2] +