Synthesis and reactions of organoiron compounds

Abstract

The multistep synthesis of the redox active adenine analog [e]-ferrocenyl-4-aminopyrimidine is reported. The redox active system will be incorporated into oligonucleotides to study the electron transfer through the molecular pi-system of DNA in future studies. Attempts were made to synthesize a cyclopenta-4-aminopyrimidine derivative which possesses an endocyclic double bond in the cyclopentane ring. This intermediate can be subsequently coupled with cyclopentadienyl iron dicarbonyl (Fp) group and, after thermal decarbonylation, form the desired ferrocene ring. Many double bond precursors are prepared, including dibromide, acetate, alcohol, ketone and phenylseleno derivatives of cyclopentapyrimidine. However efforts to form an endocyclic double bond turned out to be unsuccessful. Exocyclic double bond derivatives of cyclopentapyrimidine have also been prepared. An improved chiral synthesis of [e]-ferrocenyl-4-aminopyrimidine is achieved, in which a Curtius rearrangement to form an O-benzylcarbamate was done using a formyl ferrocene carboxylic acid. The yield of the final cyclization step was also greatly improved. The synthesis of methyl-(2,5-dimethoxy-4-fluorophenyl)-acetate, a thymine isostere precursor, is reported. It will be used as a substitute for a thymine base in a peptide nucleic acid (PNA) synthesis in the future. Regioselective bromination of 2-fluoro-hydroquinone introduced a bromo group at the desired position. After protection of hydroxyl groups in this product, a carboxylic acid ethyl ester group was introduced. Finally, an Arndt-Eistert reaction was used to extend the carboxylic acid by one carbon to the corresponding phenyl acetic acid ethyl ester. A chemical model mimicking the biosynthesis of the cyanide ligand in the enzyme hydrogenase is developed. In this model a thiocarbamate is first formed and subsequently dehydrated by polyphosphate ethyl ester(PPE) to make a thiocyanate. Finally, the cyanide moiety is transferred to the metal center. The direct dehydration of a carboxamidoiron species to form a cyano ligand is also reported.