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-R 2 -2,6- t -Bu 2 -C 6 H 2 O)(N(R 1 ) 2 )}methylidene]AuCl, where R 2 = H, R 1 = Me ( 1b ); R 2 = H, R 1 = Cy ( 2b ); R 2 = t -Bu, R 1 = Me ( 3b ); R 2 = t -Bu, R 1 = Cy ( 4b ). The mass spectrometric evidence corroborated the existence of the catalytically active solvent-coordinated [(AAOC)Au(CH 3 CN)]SbF 6 ( 1 - 4 ) A species and the acetylene-bound [(AAOC)Au(HC≡CPhMe)]SbF 6 ( 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 (NH 2 NHSO 2 C 6 H 4 CH 3 ) 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-R 2 -2,6- t -Bu 2 -C 6 H 2 O)(N(R 1 ) 2 )]CH} + OTf - ( 1 - 4 ) a by treatment with (Me 2 S)AuCl in the presence of NaH as a base. The reactivity studies of ( 1 - 4 ) b yielded the gold(III) [{(4-R 2 -2,6- t -Bu 2 -C 6 H 2 O)(N(R 1 ) 2 )}methylidene]AuBr 3 ( 1 - 4 ) c complexes upon reaction with molecular bromine and the gold(I) perfluorophenylthiolato derivatives, [{(4-R 2 -2,6- t -Bu 2 -C 6 H 2 O)(N(R 1 ) 2 )}methylidene]AuSC 6 F 5 ( 1 - 4 ) d , upon treatment with C 6 F 5 SH.