title: Development of a gold-multifaceted catalysis approach to the synthesis of highly substituted pyrroles: mechanistic insights via Huisgen cycloaddition studies.
abstract: A novel gold-catalyzed method for the regioselective synthesis of highly substituted pyrroles directly from oximes and alkynes was developed via independent optimization of two key steps of the process. Importantly, a cationic gold(I) species was shown to activate multiple steps along the reaction pathway and therefore act as a multifaceted catalyst. Initial gold-promoted addition of the oxime oxygen to the activated alkyne afforded the O-vinyloxime in situ. The O-vinyloxime was subsequently transformed into the pyrrole via a gold-catalyzed tautomerization, [3,3]-sigmatropic rearrangement, and cyclodehydration process. Notably, this method provides a functional group handle in the form of an ester at the 3/4-position for further exploitation. The proposed mechanistic pathway is supported by a novel application of the Huisgen cycloaddition click reaction, which was used to probe the relative stability of substituted O-vinyloximes. The intermediacy of N-alkenylhydroxylamine O-vinyl ethers and imino ketones or imino aldehydes along the reaction pathway were determined by high-temperature (1)H, (2)H{(1)H}, and (13)C{(1)H} NMR experiments. X-ray crystallographic evidence was used to further support the mechanistic hypothesis.
authors.affiliation: School of Chemistry, University of Nottingham, Nottingham NG7 2RD, UK.
authors.forename: Simbarashe
authors.initials: S
authors.lastname: Ngwerume
authors.forename: William
authors.initials: W
authors.lastname: Lewis
authors.forename: Jason E
authors.initials: JE
authors.lastname: Camp
mesh_terms: D000480:Alkynes / Q000737:chemistry*; D002384:Catalysis; D061565:Cycloaddition Reaction; D006046:Gold / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D010091:Oximes / Q000737:chemistry*; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000480:Alkynes; D007659:Ketones; D010091:Oximes; D011758:Pyrroles; D006046:Gold