Nickel-mediated formation of thioesters from bound methyl, thiols, and carbon monoxide: A possible reaction pathway of acetyl-coenzyme A synthase activity in nickel-containing carbon monoxide dehydrogenases

Article abstract of DOI:10.1021/ja00129a011

Current mechanistic proposals for the acetyl synthase activity of nickel-containing carbon monoxide dehydrogenases (CH₃-THF + CoA·SH → CoA·SCOCH₃ + THF; THF = tetrahydrofolate, CoA·SH = coenzyme A) implicate a Ni catalytic center and the steps [Ni-CH₃] → [Ni-COCH₃] → CoA·SCOCH₃. The second step presumably involves attack by the sulfur nucleophile of coenzyme A at the acyl carbon atom in the overall reaction [Ni^II-COCH₃] + RS(H) → RSCOCH₃ + Ni^II (+ H⁺) + 2e^-. We have previously demonstrated these steps in Ni(II) complexes with physiological-type ligation. In this work, it is shown that the reaction of acyl and thiolate ligands coordinated to Ni(II) affords thioesters in high yield. The complex [Ni(bpy)(CH₃)₂], established to be planar by an X-ray structure determination, reacts with 1 equiv of arenethiol to afford diamagnetic planar [Ni(bpy)(CH₃)(SR)] (8) with R = p-C₆H₄CH₃, 2,6-C₆H₃(CH₃)₂ (8b), mesityl (8c), 2,4,6-C₆H₂iPr₃, and 2,6-C₆H₃Cl₂ (8e) (bpy = 2,2′-bipyridyl). An analogous reaction gives [Ni(bpy)(C₂H₅)(S-mesityl)] (12) from [Ni(bpy)(C₂H₅)₂]. Planar structures of 8c,e were confirmed by X-ray analysis. Complexes 12 and 8 with different R substituents undergo thiolate ligand exchange in THF with K_eq ≈ 1. Reaction of 8e with 1 equiv of carbon monoxide yields the acyl complex [Ni(bpy)(COCH₃)(S-2,6-C₆H₃Cl₂)] (9a), whose planar coordination unit was confirmed by X-ray methods. Treatment of the complexes 8 in THF with more than 3 equiv of carbon monoxide yields [Ni(bpy)(CO)₂] and the thioesters RSCOCH₃ in 96-100% yield in situ. A solution initially containing 8b and 12 gave under the same conditions four thioesters in equal amounts, consistent with four complexes in the equilibrated solution prior to reaction with carbon monoxide. Reaction of 9a in THF with carbon monoxide produced 2,6-dichlorophenyl thioacetate quantitatively, indicating that Ni(II)-acyl-thiolate complexes are intermediates in thioester formation. The overall reaction is [Ni(bpy)(R′)(SR)] + 3CO → RSCOR′ + [Ni(bpy)(CO)₂] (R′ = CH₃, C₂H₅); the two electrons in the generalized reaction are captured by the metal as Ni(0). A related and necessarily intramolecular reaction of [Ni(bpy)(SCH₂-CH₂CH₂)] was confirmed and shown to produce γ-thiobutyrolactone in quantitative yield in situ. Evidence supporting an analogous intramolecular path for reaction systems based on 8 is summarized. This investigation provides the first examples of Ni-mediated acyclic thioester synthesis and demonstrates a possible means of enzymatic thioester formation should coenzyme A^- and an acetyl group coordinate to the Ni(II) catalytic center.