Development of a Gold-Multifaceted Catalysis Approach to the Synthesis of Highly Substituted Pyrroles: Mechanistic Insights via Huisgen Cycloaddition Studies

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 1H, 2H­{1H}, and 13C­{1H}
NMR experiments. X-ray crystallographic evidence was used to further
support the mechanistic hypothesis.