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.

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

“…Boc‐11(pept) (Boc‐Val‐Val‐Gly‐OMe): 14 Reaction of Boc‐Val‐Val‐OH (3.64 g, 11.5 mmol) with HCl·H‐Gly‐OMe (1.43 g, 11.5 mmol), triethylamine (1.60 mL, 11.5 mmol), and IIDQ (3.49 g, 11.5 mmol) yielded 3.16 g (71%) of Boc‐ 11 (pept). R f = 0.43 (ethyl acetate/cyclohexane, 3:1).…”

“…Treatment of the dipeptide derivative Boc‐Ala‐Val‐OMe with 1 furnished the analogous zirconocene cation complex 3 (after loss of methane), that was characterized by an X‐ray crystal structure analysis. It revealed the formation of a metallatricyclic structure analogous to 2 (see Scheme ), that again exhibits very typical 1 H and 13 C NMR features 14…”

“…A series of experiments using different di‐ and tripeptide systems revealed that [Cp 2 ZrCH 3 + ] was in all the cases first attached to the C4 carbonyl oxygen atom under kinetic control, followed by migration of the metallocene unit along the chain. Subsequent intramolecular NH deprotonation with loss of CH 4 usually led to the formation of complex 4 (chel) (with a few exceptions), which is the thermodynamic product in the series investigated14 (see Scheme ).…”

Synthesis and structural characterization of Group 4 metallocene complexes that contain remote carboxamide functionalities at their Cp-side chains

“…It is thus shifted by ∆δ = 7.5 ppm to low field, which is clear indication that the C᎐ ᎐ O group is oxygen-coordinated intramolecularly to the Lewis-acidic cationic titanium center. 30 The 15 N NMR chemical shift is actually only slightly affected by this coordination (measured at 16[BuB(C 6 F 5 ) 3 Ϫ ]: δ Ϫ254 vs. Ϫ258 observed in 13b, see above).…”

Bio-Organometallic Chemistry, ansa-Metallocenes, and Frustrated Lewis Pairs: Functional Group Chemistry at the Group 4 Bent Metallocenes

“…In some cases we were able to monitor an equilibration with a second κO isomer ( 14b ), formally derived from migration of the titanocene moiety along the chain. Eventually, internal deprotonation of the peptide backbone took place with methane evolution to yield the chelate−peptide titanocene cation products 15 (see Scheme ). , …”