Conformational analysis of heteroannularly substituted ferrocene oligoamides

Article abstract of DOI:10.1002/ejic.200601230

The main conformer of symmetrical conjugates of ferrocene-1,1′- dicarboxylic acid with natural amino acids - Fn(CO-AA_1-2-OMe) ₂ (type I, Fn = ferrocene-1,1′-diyl, AA = L-α-amino acid) - is supported by two hydrogen bonds between the peptide substituents. To compare intramolecular hydrogen bond patterns of type I conjugates with related asymmetrically substituted derivatives, type II (MeNHCO-Fn-CO-AA-OMe) and type III conjugates (MeNHCO-Fn-CO-AA-NHMe) were prepared in moderate-to-good yields in a few steps starting from 1′-(methoxycarbonyl)ferrocene-1-carboxylic acid by using the HOBt/EDC method (AA = Gly, Ala, Val). ¹H NMR spectroscopic variation ratio analysis suggests that an increase in the steric demand of the amino acid side chains favours conformations with hydrogen-bonded FnCONHMe groups. CD spectroscopy of chiral derivatives reveals that (P)-helical conformations predominate in solution. The experimental findings are in accordance with DFT calculations. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.