Group-4 metallocene cation complexes of oligopeptides: Reaction of [Cp2ZrCH3(THF)+BPh4-] with Boc-protected di- and tripeptide esters

The dipeptide derivatives Boc-Gly-Val-OMe (2) and Boc-Ala-Val-OMe (3) selec tively add the methylzirconocene cation 1 to the carbonyl oxygen atom of th e N-terminal amino acid residue (kappa-C-4=O coordination) upon treatment w ith [Cp2ZrCH3 (THF)+BPh4-] in dichloromethane at low temperature (<0 degree s C) to generate the complexes 2-I and 3-I, respectively. Above 0 degrees C methane is eliminated to give the stable chelate peptide metallocene catio n complexes 2-A and 3-A, respectively, both featuring a combined C-1=O/N2/C -4=O coordination to the zirconium center. Complex 3-A was characterized by X-ray diffraction. The analogous tripeptide derivatives Boc-Gly-Val-Val-OM e (6), Boc-Ala-Ala-Val-OMe (7), Boc-Ala-Val-Val-OMe (8), and Boc-Val-Val-Gl y-OMe (9) all form analogous kappa-C-4=O Cp2ZrCH3+ cation adducts (6-9) - u nder kinetic control and after subsequent loss of CH4 C-1=O/N2/C-4=O chelat e complexes (6-9)-A under thermodynamic control, both involving selective b onding of the organometallic cation to the terminal amino acid residue of t he respective peptide derivatives. Thermolysis of the primary adduct 7-I (> 0 degrees 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 detaile d NMR analysis 7-A shows the favored chelate coordination at the N-terminus involving C-1=O/N2/C-4=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 Liberat ion from 8-I and 9-I gave mixtures of the respective cationic chelate compl ex isomers 8-A/8-C (2:3) and 9-A/9-C (1:1), respectively. The (8,9)-A isome rs 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 este r carbonyl group in forming the chelate framework (C-7=O/N8/C-10=O coordina tion). The (6-9)-A isomers are thermodynamically favored. The cation comple xes 7-B, 8-C, 9-C rearrange to the A-type isomers upon prolonged standing a t temperatures >0 degrees C in dichloromethane solution.