Group-4 Metallocene Cation Complexes of Oligopeptides: Reaction of [Cp2ZrCH3(THF)+BPh4−] with Boc-Protected Di- and Tripeptide Esters

Abstract

The dipeptide derivatives Boc-Gly-Val-OMe (2) and Boc-Ala-Val-OMe (3) selectively add the methylzirconocene cation 1 to the carbonyl oxygen atom of the N-terminal amino acid residue (ĸ-C4=O coordination) upon treatment with [Cp2ZrCH3(THF)+BPh4−] in dichloromethane at low temperature (< 0 °C) to generate the complexes 2-I and 3-I, respectively. Above 0 °C methane is eliminated to give the stable chelate peptide metallocene cation complexes 2-A and 3-A, respectively, both featuring a combined C1=O/N2/C4=O coordination to the zirconium center. Complex 3-A was characterized by X-ray diffraction. The analogous tripeptide derivatives Boc-Gly-Val-Val-OMe (6), Boc-Ala-Ala-Val-OMe (7), Boc-Ala-Val-Val-OMe (8), and Boc-Val-Val-Gly-OMe (9) all form analogous ĸ-C4=O Cp2ZrCH3+ cation adducts (6–9)-I under kinetic control and after subsequent loss of CH4 C1=O/N2/C4=O chelate complexes (6–9)-A under thermodynamic control, both involving selective bonding of the organometallic cation to the terminal amino acid residue of the respective peptide derivatives. Thermolysis of the primary adduct 7-I (> 0 °C) resulted in methane elimination and formation of a mixture of the isomers 7-B and 7-A (isolated in a 3:4 ratio). According to the detailed NMR analysis 7-A shows the favored chelate coordination at the N-terminus involving C1=O/N2/C4=O bonding, whereas the cation complex 7-B exhibits a similar chelate structure at the internal Ala moiety, characterized by C4=O/N5/C7=O coordination to the zirconium center. Similarly, methane liberation from 8-I and 9-I gave mixtures of the respective cationic chelate complex isomers 8-A/8-C (2:3) and 9-A/9-C (1:1), respectively. The (8,9)-A isomers have the zirconium ion bonded at the N-terminus, whereas (8,9)-C exhibit the Cp2Zr+ unit at the C-terminus of the peptide chain, involving the ester carbonyl group in forming the chelate framework (C7=O/N8/C10=O coordination). The (6–9)-A isomers are thermodynamically favored. The cation complexes 7-B, 8-C, 9-C rearrange to the A-type isomers upon prolonged standing at temperatures > 0 °C in dichloromethane solution.