The mild chlorination of small-molecules and natural products provides complex synthetic intermediates for modern transition metal-catalyzed couplings. Most current catalytic electrophilic aromatic chlorinations generally rely on the innate reactivity of the molecule, often yielding a complex mixture of regioisomers. We recently disclosed a mild Lewis base catalyzed halogenation of diverse arenes and heterocycles that closely follows the trend in innate selectivity. In an attempt to overcome this inherent selectivity, we hypothesized that the introduction of catalyst functionality that can interact with the substrate would direct electrophilic aromatic substitution away from the innate reactivity. Herein, we have found that different Lewis base catalysts can augment or overcome the innate regioselectivity of substituted phenols and other functionalized arenes. This work opens the door for mild, catalyst-directed electrophilic aromatic substitutions on both simple and complex arenes.

Lewis-base catalyzed regioselective chlorination of activated aromatic compounds

251st National Meeting (2016)

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