Reaction of [(Cp2TiCH3)(THF)+][BPh4] with Tripeptide Derivatives: Formation of Cationic (Peptide)titanocene Complexes

Abstract

A series of Z- and Boc-protected tripeptide methyl esters [Z-/Boc-5 to -12(pept)] was prepared using the amino acids glycine, alanine and valine. In both the alanine and the valine series a single glycine unit was introduced and its position inside the tripeptide framework was systematically varied. Reaction of these 16 tripeptide derivatives with the organometallic reagent [Cp2TiCH3(THF)+][BPh4−] (13) resulted in the formation of methyl(peptide)titanocene cation complexes that contained the strongly electrophilic [Cp2TiCH3+] cation moiety coordinated to a single carboxamide carbonyl oxygen atom. Mostly, the carbonyl oxygen atom of the central amino acid residue was specifically attached to yield the coordination products 5−12(coord7). In a few specific cases, formation of the κO-adduct between the [Cp2TiCH3+] cation and the N-terminal amino acid moiety was also observed, especially in the cases of the N-terminal glycine derivatives. In one case we observed the migration of the [Cp2TiCH3+] group along the chain from the C4=O to the C7=O position. Subsequent thermally induced CH4 elimination of the products 5−12(coord) gave the cationic peptide chelate derivatives 5−12(chel). These are characterized by the presence of a five-membered κO,κN-chelate with an anellated four-membered κN,κO-chelate. This is mostly centered around the central amino acid unit [products 5−12(chelB)], but in some cases the N-terminal amino acid, together with the N-terminal protective group, also forms this type of a stable peptide titanocene cation chelate complex [products 5−12(chelA)]. The selective formation of these series of (peptide)metallocene cation complexes was readily analyzed by means of their very characteristic 1H and 13C NMR spectra. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)