We outline a strategy to enable non-directed C�H functionalization in the presence of Lewis basic heterocycles. In a high-throughput screen study of C�H functionalization reactions, addition of a variety of N-heterocycles are found to cause low product conversion. A pyridine-containing test substrate is selected as representative of heterocyclic scaffolds that are hypothesized to cause catalyst arrest. We pursue two approaches in parallel that allow product conversion in this representative system: Lewis acids are found to be effective in situ blocking groups for the Lewis basic site, and a pre-formed pyridine N-oxide is shown to enable high yield of C�H oxidation. Computational studies with density functional theory (M06) of binding affinities of selected heterocycles to Pd(OAc)2 gave an inverse correlation of the computed heterocycle�Pd(OAc)2 binding affinities with the experimental conversions to products.

Strategies to study and enable non-directed C�H functionalization in the presence of Lewis basic heterocycles

247th National Meeting (2014)

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