Thiamine is a water-soluble vitamin, which through its pyrophosphorylated derivative thiamine diphosphate (ThDP), serves as an enzyme cofactor in a multitude of biomolecular reactions via ylide/carbene chemistry. The transient N-heterocyclic carbene (NHC) species generated during its biocatalysis is an attractive ligand for transition metal catalysts as it can confer on them enhanced water solubility and potentially novel activity. A water-soluble NHC-Au(I)Cl complex of thiamine was synthesized by the in situ generation of a thiazolin-2-ylidine carbene from thiamine hydrochloride in the presence of chloro(dimethylsulfide)gold(I) and was thoroughly characterized by ¹H NMR, ¹³C NMR and ESI-HRMS. This complex was utilized as a green catalyst for the A³ coupling reaction. Its catalytic acti...[ Read more ]

Thiamine is a water-soluble vitamin, which through its pyrophosphorylated derivative thiamine diphosphate (ThDP), serves as an enzyme cofactor in a multitude of biomolecular reactions via ylide/carbene chemistry. The transient N-heterocyclic carbene (NHC) species generated during its biocatalysis is an attractive ligand for transition metal catalysts as it can confer on them enhanced water solubility and potentially novel activity. A water-soluble NHC-Au(I)Cl complex of thiamine was synthesized by the in situ generation of a thiazolin-2-ylidine carbene from thiamine hydrochloride in the presence of chloro(dimethylsulfide)gold(I) and was thoroughly characterized by ¹H NMR, ¹³C NMR and ESI-HRMS. This complex was utilized as a green catalyst for the A³ coupling reaction. Its catalytic activity matched or exceeded other common A³ coupling catalysts while tolerating a broad range of substrates. A new class of artificial metalloenzymes based on the supramolecular anchoring of ThDP to bacterial enzyme MenD was envisioned; this system aims to promote asymmetric organometallic catalysis in the aqueous and chiral environment of the MenD active site. To this end, the synthesis of a ThDP-AuCl NHC complex was attempted. Attempts at direct synthesis of the complex were not successful. Several strategies towards the indirect synthesis of the complex via the characterized thiamine-AuCl NHC complex were attempted instead, but they too did not yield the desired product. Miscellaneous investigations were conducted which uncovered the relatively unexplored chemistry of thiazolin-2-ylidine carbene metal complexes, helping to rationalize some observations of performed experiments.