Ngwerume, Simbarashe, Lewis, William and Camp, Jason (2013) Development of a Gold-Multifaceted Catalysis Approach to the Synthesis of Highly Substituted Pyrroles: Mechanistic Insights via Huisgen Cycloaddition Studies. Journal of Organic Chemistry, 78 (3). pp. 920-934. ISSN 0022-3263

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 addn. 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 cycloaddn. 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 detd. by high-temp. 1H, 2H{1H}, and 13C{1H} NMR expts. X-ray crystallog. evidence was used to further support the mechanistic hypothesis. [on SciFinder(R)]

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