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.