Accessing Bioactive Hydrazones by the Hydrohydrazination of Terminal Alkynes Catalyzed by Gold(I) Acyclic Aminooxy Carbene Complexes and Their Gold(I) Arylthiolato and Gold(III) Tribromo Derivatives: A Combined Experimental and Computational Study

Hydrohydrazination of terminal alkynes with hydrazides yielding hydrazones 5-14 were successfully catalyzed by a series of gold(I) acyclic aminooxy carbene complexes of the type [{(4-R²-2,6-t-Bu₂-C₆H₂O)(N(R¹)₂)}methylidene]AuCl, where R² = H, R¹ = Me (1b); R² = H, R¹ = Cy (2b); R² = t-Bu, R¹ = Me (3b); R² = t-Bu, R¹ = Cy (4b). The mass spectrometric evidence corroborated the existence of the catalytically active solvent-coordinated [(AAOC)Au(CH₃CN)]SbF₆ (1-4)A species and the acetylene-bound [(AAOC)Au(HC≡CPhMe)]SbF₆ (3B) species of the proposed catalysis cycle. The hydrohydrazination reaction was successfully employed in synthesizing several bioactive hydrazone compounds (15-18) with anticonvulsant properties using a representative precatalyst (2b). The DFT studies favored the 4-ethynyltoluene (HC≡CPhMe) coordination pathway over the p-toluenesulfonyl hydrazide (NH₂NHSO₂C₆H₄CH₃) coordination pathway, and that proceeded by a crucial intermolecular hydrazide-assisted proton transfer step. The gold(I) complexes (1-4)b were synthesized from the {[(4-R²-2,6-t-Bu₂-C₆H₂O)(N(R¹)₂)]CH}⁺OTf^- (1-4)a by treatment with (Me₂S)AuCl in the presence of NaH as a base. The reactivity studies of (1-4)b yielded the gold(III) [{(4-R²-2,6-t-Bu₂-C₆H₂O)(N(R¹)₂)}methylidene]AuBr₃ (1-4)c complexes upon reaction with molecular bromine and the gold(I) perfluorophenylthiolato derivatives, [{(4-R²-2,6-t-Bu₂-C₆H₂O)(N(R¹)₂)}methylidene]AuSC₆F₅ (1-4)d, upon treatment with C₆F₅SH.